Genere e demenze

Amalia C Bruni

Centro Regionale di Neurogenetica

Lamezia Terme

ASP CZ

Padova 27 novembre 2017

2

Global world challenges

Increasing world population

Feeding the population withsafer healthier higherndashquality

food through a sustainableagriculture

Ageing population

Functional and cognitive decline

Diet-related diseases

Metabolic Disorders Allergies Obesityhellip

Depression

Life expectancy and gender difference

Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso

Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)

ANNICLASSI DI ETArsquo

1 malattia cronica o piugrave

2 malattie croniche o piugrave

Diabete Ipertensione Malattie del cuore

2009 388 203 48 158 26

2010 386 201 49 160 37

2011 384 200 49 159 36

2012 386 204 55 164 35

2013 379 200 54 167 37

2013 ndash Per classi di etagrave e sessoMASCHI

60-64 610 304 130 330 69

65-74 728 422 160 452 116

75 e oltre 828 587 207 504 198

2013 ndash Per classi di etagrave e sessoFEMMINE

60-64 664 394 77 319 32

65-74 781 544 143 447 67

75 e oltre 886 739 201 576 144

Istat 2013

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

2

Global world challenges

Increasing world population

Feeding the population withsafer healthier higherndashquality

food through a sustainableagriculture

Ageing population

Functional and cognitive decline

Diet-related diseases

Metabolic Disorders Allergies Obesityhellip

Depression

Life expectancy and gender difference

Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso

Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)

ANNICLASSI DI ETArsquo

1 malattia cronica o piugrave

2 malattie croniche o piugrave

Diabete Ipertensione Malattie del cuore

2009 388 203 48 158 26

2010 386 201 49 160 37

2011 384 200 49 159 36

2012 386 204 55 164 35

2013 379 200 54 167 37

2013 ndash Per classi di etagrave e sessoMASCHI

60-64 610 304 130 330 69

65-74 728 422 160 452 116

75 e oltre 828 587 207 504 198

2013 ndash Per classi di etagrave e sessoFEMMINE

60-64 664 394 77 319 32

65-74 781 544 143 447 67

75 e oltre 886 739 201 576 144

Istat 2013

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Depression

Life expectancy and gender difference

Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso

Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)

ANNICLASSI DI ETArsquo

1 malattia cronica o piugrave

2 malattie croniche o piugrave

Diabete Ipertensione Malattie del cuore

2009 388 203 48 158 26

2010 386 201 49 160 37

2011 384 200 49 159 36

2012 386 204 55 164 35

2013 379 200 54 167 37

2013 ndash Per classi di etagrave e sessoMASCHI

60-64 610 304 130 330 69

65-74 728 422 160 452 116

75 e oltre 828 587 207 504 198

2013 ndash Per classi di etagrave e sessoFEMMINE

60-64 664 394 77 319 32

65-74 781 544 143 447 67

75 e oltre 886 739 201 576 144

Istat 2013

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Life expectancy and gender difference

Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso

Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)

ANNICLASSI DI ETArsquo

1 malattia cronica o piugrave

2 malattie croniche o piugrave

Diabete Ipertensione Malattie del cuore

2009 388 203 48 158 26

2010 386 201 49 160 37

2011 384 200 49 159 36

2012 386 204 55 164 35

2013 379 200 54 167 37

2013 ndash Per classi di etagrave e sessoMASCHI

60-64 610 304 130 330 69

65-74 728 422 160 452 116

75 e oltre 828 587 207 504 198

2013 ndash Per classi di etagrave e sessoFEMMINE

60-64 664 394 77 319 32

65-74 781 544 143 447 67

75 e oltre 886 739 201 576 144

Istat 2013

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Popolazione residente per condizione di salute malattie croniche dichiarate negli ultimi due giorni precedenti lrsquointervista classe di etagrave sesso

Anno 2013 (per 100 persone della stessa classe di etagrave e sesso)

ANNICLASSI DI ETArsquo

1 malattia cronica o piugrave

2 malattie croniche o piugrave

Diabete Ipertensione Malattie del cuore

2009 388 203 48 158 26

2010 386 201 49 160 37

2011 384 200 49 159 36

2012 386 204 55 164 35

2013 379 200 54 167 37

2013 ndash Per classi di etagrave e sessoMASCHI

60-64 610 304 130 330 69

65-74 728 422 160 452 116

75 e oltre 828 587 207 504 198

2013 ndash Per classi di etagrave e sessoFEMMINE

60-64 664 394 77 319 32

65-74 781 544 143 447 67

75 e oltre 886 739 201 576 144

Istat 2013

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Dementia subtypes

Nel mondo un caso di demenza ogni tre secondi

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

TIMELINE DEMENZE

LEWY

VASCULAR

AD

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Podcasy and Epperson Dialogues in Clinical Neuroscience - Vol 18 No 4 2016

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Un soggetto su nove ha la malattia di Alzheimer e le donne sono il doppio

(gt65 anni)

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Studio ILSA Incidenza della malattia di Alzheimer e della demenza vascolare per sesso e classi di etagrave

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 100

0

0

3

6

9

12

15

18

65-69 70-74 75-79 80-84

Classi di etagrave

Inci

denz

a pe

r 10

00

Uomini Donne

AD VaD

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Metanalysis 12784 ALS patients

Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN mediatedphenotypic expression

Curtis et al Neurologyreg 2017891ndash10

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

A cosa DOBBIAMO QUESTE DIFFERENZE

DIFFERENTE PESO DEI FATTORI DI RISCHIO

DIFFERENTI CONNESSIONI E NETWORK

DIFFERENTE BACKGROUND ORMONALE

DIFFERENTE ESPRESSIONEASSETTO GENETICO

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Gender differences in behavioraland cognitive functioning

bull The brain can be considered as a large-scale network of interconnected nodes within the human connectome

bull Small world network (network di connessione tra nodi))

Gender differences in brain connectome mayprovide an important foundation to delineate thepathophysiological mechanisms underlying sexdifferences in neuropsychiatric disorders and to potentially guide the development of sex specifictreatments

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Differenti comunicazioni maschi in blu (percezione-azione coordinata)donne in arancio (analitico-intuitivo)

Ingalhalikar et al 2013

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Mosconi et al Neurology 2017

Differenze ormonali

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

These results indicate progressively increased risk of AD as women undergo menopausal changes suggesting that endocrine aging accelerates chronologic aging in the female brain several years if

not decades prior to emergence of possible clinical symptoms of AD

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

AD

Ris

k

40yrs

OVARIECTOMY

Timing hypothesis

50yrs

Rocca et al 2011

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Approximately 650 genes

(~ 14 of all genes in mouse

tissue) are expressed

differentially in the brains of

males and females The

morphology of the brain may

be sexually differentiated

because of epigenetic

mechanisms

Yang X et al (2006) Tissue-specific expression and regulationof sexually dimorphic genes in mice Genome Research 16 (8) 995-1004

Murray E K et al (2009) Epigenetic Control of SexualDifferentiation of the Bed Nucleus of the Stria Terminalis Endocrinology 150 (9) 4241-4247

Genes differences

Diversa espressione dei geni nei cervelli di maschi e femmine

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Sex differences in metabolic aging of the brain insights into female susceptibility to Alzheimerrsquos disease

bull Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains

bull In female brains 442 of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation

bull In contrast in male brains only 54 in the same period

Zhao et al Neurobiol Aging 2016 June 42 69ndash79 doi101016jneurobiolaging201602011

Conclusions female and male brains follow profoundly dissimilar trajectories as they age female brains undergo age-related changes much earlier than male brains early changes in female brains signal the onset of a hypometabolicphenotype at risk for AD

These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Differente espressione di SRY in aree cerebrali

HLoke et al The International Journal of Biochemistry amp Cell Biology 65 (2015) 139ndash150

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Male and female brains are neurochemicallydistinct concerning dopaminergic serotonergic and gamma-aminobutyric acid (GABA)ergic markers

Cosgrove KP et al Biol Psychiatry 2007 Oct 1562(8)847-55 Epub 2007 Jun 4

Sex-specific differences in neuromediators

Serotonin sexually differentiated multiple levels

Risk factors

Female sex early-onset hypertension and risk of dementia

Gilsanz et al Neurologyreg 2017891ndash8

Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men

Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive

Midlife hypertension was more common in men however itwas associated with dementia risk only in women

APOE4 effect is more pronounced in women than in men

HZ carrier APOEe4 earlier age at onset of AD

3-4 times more likely to develop AD

FARRER ET AL 1997

Fattori di rischio geneticihanno pesi diversi

ApoE4 strongly promotes amyloid-β deposition in the brain

Liu et al Nat Rev Neurol 2013

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Risk factors

Female sex early-onset hypertension and risk of dementia

Gilsanz et al Neurologyreg 2017891ndash8

Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men

Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive

Midlife hypertension was more common in men however itwas associated with dementia risk only in women

APOE4 effect is more pronounced in women than in men

HZ carrier APOEe4 earlier age at onset of AD

3-4 times more likely to develop AD

FARRER ET AL 1997

Fattori di rischio geneticihanno pesi diversi

ApoE4 strongly promotes amyloid-β deposition in the brain

Liu et al Nat Rev Neurol 2013

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Female sex early-onset hypertension and risk of dementia

Gilsanz et al Neurologyreg 2017891ndash8

Mid-adulthood hypertension wasassociated with 65 (95confidenceinterval [CI]125ndash218) increased dementia risk amongwomen but not men

Onset of hypertension in mid-adulthood predicted 73 higherdementia risk in women (95 CI 124ndash240) compared to stablenormotensive

Midlife hypertension was more common in men however itwas associated with dementia risk only in women

APOE4 effect is more pronounced in women than in men

HZ carrier APOEe4 earlier age at onset of AD

3-4 times more likely to develop AD

FARRER ET AL 1997

Fattori di rischio geneticihanno pesi diversi

ApoE4 strongly promotes amyloid-β deposition in the brain

Liu et al Nat Rev Neurol 2013

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

APOE4 effect is more pronounced in women than in men

HZ carrier APOEe4 earlier age at onset of AD

3-4 times more likely to develop AD

FARRER ET AL 1997

Fattori di rischio geneticihanno pesi diversi

ApoE4 strongly promotes amyloid-β deposition in the brain

Liu et al Nat Rev Neurol 2013

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

ApoE4 strongly promotes amyloid-β deposition in the brain

Liu et al Nat Rev Neurol 2013

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Risk gender for dementia or AD

In all three examples women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval) Panel A APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow) Panel B low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red

Rocca et al Maturitas 2014 October 79(2) 196ndash201 doi101016jmaturitas201405008

Men blueWomen red

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

APOE Meta analysis

JAMANeuroldoi101001jamaneurol20172188 PublishedonlineAugust282017

Increased risk in womenbetween 65-75 yrs

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Risk factors in 1925 AD patients

Notaro P doctoral thesis 2017Unical

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Le demenze sono molto variabili nei loro fenotipi

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

female patients with DLB having a higher frequency of VH symptoms

Chiu et al Int J Geriatr Psychiatry 2017

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Women show an advantage in verbal memory despite evidence of moderate hippocampalatrophy This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages

lrsquoanalisi dei gruppi evidenziache queste donne hanno piugrave di 15 anni di

scolaritagrave

Cognitive reserve

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

IN SINTESIhellip

bull Le donne sono maggiormente a rischio per demenza e specie per malattia di Alzheimer tutto sembra concorrere a farle ammalare di piugrave dei maschi

bull Lrsquo assetto genetico e ormonale il modo di connettere informazioni a livello cerebrale le tante malattie in piugrave il piugrave basso livello di scolaritagrave e la minore attivitagrave laquosocialeraquo rispetto ai maschihelliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Take home messages

bull Le differenze di genere osservate nelle demenze ( per tipo sintomied espressione fenotipica) originano dale profonde differenzecerebrali (genetiche ormonali e di connessioni) che esistono tra I due sessi

bull La consapevolezza e la ricerca in questa direzione potrebberoportare in futuro ad avere trattamenti genere - specifici non solo per gli aspetti cognitivi ma ancora di piugrave per quelli comportamentali

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Il ogni caso il futuro egrave disegnatohellip studiare di piugrave avere una maggiore vita sociale fare attivitagrave fisica combattere le malattiehelliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

Anno 1791 giorno 29 Dicembre helliphelliphelliphellip Magnifica Eleonora Miceli helliphelliphelliphelliphelliphelliphellipanni sei sopra cento helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellipin giusto ragionamento ed intelligenza dei sensihelliphelliphelliphelliphelliphellip

Serrastretta Parish Archives

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip

She does not recognize anybody she does not understand anything she does not answer any questions and she is emotionally flat She stays in bed all day moving her eyes around without any kind of thoughts driving her mind or triggering any movements of her limbs She mumbles incomprehensible words She seems astonished and scaredrsquorsquo

She died of marasmus at the age of 40 yearsin 1905helliphellip