alzheimer hellas 3rd department of neurology, medical school,
DESCRIPTION
Longitudinal cognitive training changes the conversion’s rate of Mild Cognitive Impairment to dementia. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/1.jpg)
1. Alzheimer Hellas
2. 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Greece
1. Alzheimer Hellas
2. 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Greece
Longitudinal cognitive training changes the conversion’s rate of
Mild Cognitive Impairment to dementia
Kounti, F.1, Poptsi, E.1, Agogiatou, C.1, Bakoglidou, E. 1, Soumpourou A. 1, Zafeiropoulos, S. 1, Batsila G. 1, Nikolaidou,
E. 1, Vasiloglou, M. 1, Ouzouni, F. 1, Markou N. 1, Zafeiropoulou, M. 1, Tsolaki, M. 1, 2
![Page 2: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/2.jpg)
Mild Cognitive Impairment
Mild Cognitive Impairment
MCI represents a transitional state between the cognitive changes of aging and the earliest clinical features of dementia
(Petersen, 2003; Petersen et al., 2001)
MCI patients are at increased risk for the development of dementia
(Bruscoli & Lovestone, 2004; Petersen, 2004)
MCI represents a transitional state between the cognitive changes of aging and the earliest clinical features of dementia
(Petersen, 2003; Petersen et al., 2001)
MCI patients are at increased risk for the development of dementia
(Bruscoli & Lovestone, 2004; Petersen, 2004)
![Page 3: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/3.jpg)
MCI patients progress to dementia at very different
rates
MCI patients progress to dementia at very different
rates
aMCImd patients appear to be at greatest risk for future dementia(Di Carlo et al., 2007; Palmer et al., 2008; Tabert et al., 2006 Ravaglia et al., 2006)
Less than 20% of patients with aMCImd revert to normal aging (Loewenstein, et al., 2009)
Others remain stable upon retest(Bickel et al., 2006)
aMCImd patients appear to be at greatest risk for future dementia(Di Carlo et al., 2007; Palmer et al., 2008; Tabert et al., 2006 Ravaglia et al., 2006)
Less than 20% of patients with aMCImd revert to normal aging (Loewenstein, et al., 2009)
Others remain stable upon retest(Bickel et al., 2006)
![Page 4: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/4.jpg)
Neurogenesis in aging (hippocampus)
Neurogenesis in aging (hippocampus)
![Page 5: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/5.jpg)
ChEIs and Mild Cognitive Impairment
ChEIs and Mild Cognitive Impairment
ChEIs in patients with MCI are not associated with any delay in the onset of dementia The risks associated with ChEIs are not negligible(Raschetti et al., 2007)
It is important to study the possibility of cognitive training to improve cognitive and functional performance
ChEIs in patients with MCI are not associated with any delay in the onset of dementia The risks associated with ChEIs are not negligible(Raschetti et al., 2007)
It is important to study the possibility of cognitive training to improve cognitive and functional performance
![Page 6: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/6.jpg)
Aims of non pharmacological
therapies
Aims of non pharmacological
therapiesAim of cognitive therapy:
Cognitive improvementDelay of conversion rate to dementia
Expected results:Reactivation of atrophic neurons in patients with MCI(Swabb, 1994) Maintenance of regenerated neurons after cognitive training for a long period of time
Aim of cognitive therapy:Cognitive improvementDelay of conversion rate to dementia
Expected results:Reactivation of atrophic neurons in patients with MCI(Swabb, 1994) Maintenance of regenerated neurons after cognitive training for a long period of time
![Page 7: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/7.jpg)
The studyThe study
aMCImd patients
Non pharmacological therapy (cognitive training)
64 sessions (in a period of 2 years)
2 groups (experimental and control)
aMCImd patients
Non pharmacological therapy (cognitive training)
64 sessions (in a period of 2 years)
2 groups (experimental and control)
![Page 8: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/8.jpg)
Study hypothesesStudy hypotheses
Experimental group:Improvement of targeted cognitive abilities (attention - parameters of executive function) Generalization of cognitive benefit in other cognitive domains through the consolidation of new learningDelay of conversion rate to dementia
Control Group:Stability of cognitive performance, a slight deterioration or a slight improvement, two years after the initial assessment
Experimental group:Improvement of targeted cognitive abilities (attention - parameters of executive function) Generalization of cognitive benefit in other cognitive domains through the consolidation of new learningDelay of conversion rate to dementia
Control Group:Stability of cognitive performance, a slight deterioration or a slight improvement, two years after the initial assessment
![Page 9: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/9.jpg)
ParticipantsParticipants
Inclusion criteria:60 years of age
Subjective cognitive complaints
aMCImd diagnosis (Petersen’s criteria 2001)
MMSE: 26-30 points
Spared language skills(speech comprehension or production)
Inclusion criteria:60 years of age
Subjective cognitive complaints
aMCImd diagnosis (Petersen’s criteria 2001)
MMSE: 26-30 points
Spared language skills(speech comprehension or production)
![Page 10: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/10.jpg)
ParticipantsParticipants
Exclusion criteria:Diagnosis of dementia
(NINCDS-ADRDA criteria-McKahnn et al., 1984)Severe psychotic traits (untreated depression, agitation or behavioral problems) Other neurological disorders (stroke or ischemic lesions)AntipsychoticsChEIsDifficulties in sensory abilities
Exclusion criteria:Diagnosis of dementia
(NINCDS-ADRDA criteria-McKahnn et al., 1984)Severe psychotic traits (untreated depression, agitation or behavioral problems) Other neurological disorders (stroke or ischemic lesions)AntipsychoticsChEIsDifficulties in sensory abilities
![Page 11: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/11.jpg)
ParticipantsParticipants
Outpatients of the memory and dementia clinic of “G.Papanikolaou” General Hospital and of the day care centers of Alzheimer HellasArea of Northern HellasPatients visited these sources voluntarily and signed an informed consent
Outpatients of the memory and dementia clinic of “G.Papanikolaou” General Hospital and of the day care centers of Alzheimer HellasArea of Northern HellasPatients visited these sources voluntarily and signed an informed consent
![Page 12: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/12.jpg)
ParticipantsParticipants
![Page 13: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/13.jpg)
ParticipantsParticipants
No statistically significant differences between the two groups at baseline
In age, education, gender, cognitive and functional performance
Controls did not take part in any kind of cognitive therapy
They continued their regular daily activities
No statistically significant differences between the two groups at baseline
In age, education, gender, cognitive and functional performance
Controls did not take part in any kind of cognitive therapy
They continued their regular daily activities
![Page 14: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/14.jpg)
Sample CharacteristicsSample Characteristics
Characteristics/Cognitive/Functional Performance*M (SD)
Control Group (n=45)
Experimental Group (n=95)
p
Age 68.00
(8.62)
60.01 (7.34) .312
Gender (Male/Female) Fisher’s test .073
Education 10.40
(4.11)
11.17 (4.44) .117
Global cognitive function (Total MMSE) 28.28
(1.35)
27.71 (1.77) .046
Global cognitive function (Total MoCA) 23.23
(2.84)
23.05 (2.79) .328
ADL (Total FRSSD) 4.33 (1.73) 3.83 (1.92) .081
ADL (Total FUCAS) 43.00
(1.34)
43.34 (1.33) .060
![Page 15: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/15.jpg)
Neuropsychological assessment
Neuropsychological assessment
1st assessment: at baseline
2nd assessment: 2 years later, at the end of the therapy
1st assessment: at baseline
2nd assessment: 2 years later, at the end of the therapy
![Page 16: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/16.jpg)
Neuropsychological battery
Neuropsychological battery
MEMORYRivermead Behavioral Memory test (RBMT)Rey Auditory Verbal Learning Test (RAVLT)Rey – Osterrieth Complex figure Test (ROCFT)
ATTENTIONTest of Everyday Attention (TEA) WAIS-R (DIDIT SYMBOL)
LANGUAGEBoston Naming Test (BNT)Verbal fluency test (ΧΣΑ)
MEMORYRivermead Behavioral Memory test (RBMT)Rey Auditory Verbal Learning Test (RAVLT)Rey – Osterrieth Complex figure Test (ROCFT)
ATTENTIONTest of Everyday Attention (TEA) WAIS-R (DIDIT SYMBOL)
LANGUAGEBoston Naming Test (BNT)Verbal fluency test (ΧΣΑ)
EXECUTIVE FUNCTION Wisconsin Card Sorting Test (WCST)Trail-making Test Part B (TRAIL B)Stroop Color Word test (SCWT)Functional Cognitive Assessment Scale (FUCAS-EXECUTIVE FUNCTION)
GENERAL COGNITIVE FUNCTIONMini Mental State Examination (MMSE)Montreal Cognitive Assessment (MoCA)
ADLFunctional Rating Scale of Symptoms of Dementia (FRSSD)Functional Cognitive Assessment Scale (FUCAS-ADL)
EXECUTIVE FUNCTION Wisconsin Card Sorting Test (WCST)Trail-making Test Part B (TRAIL B)Stroop Color Word test (SCWT)Functional Cognitive Assessment Scale (FUCAS-EXECUTIVE FUNCTION)
GENERAL COGNITIVE FUNCTIONMini Mental State Examination (MMSE)Montreal Cognitive Assessment (MoCA)
ADLFunctional Rating Scale of Symptoms of Dementia (FRSSD)Functional Cognitive Assessment Scale (FUCAS-ADL)
![Page 17: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/17.jpg)
Therapeutic techniquesTherapeutic techniques
Cognitive Training techniques of Attention and Cognitive Parameters of Executive Function through:Paper and pencil tasks Kinetic instructions Mental Imagery under Relaxation Musical Stimuli Reality Orientation in Currents EventsComputer softwareEach trainee took part in a specific therapeutic combination of techniques, related to his/her residual abilities and impaired functions
Cognitive Training techniques of Attention and Cognitive Parameters of Executive Function through:Paper and pencil tasks Kinetic instructions Mental Imagery under Relaxation Musical Stimuli Reality Orientation in Currents EventsComputer softwareEach trainee took part in a specific therapeutic combination of techniques, related to his/her residual abilities and impaired functions
![Page 18: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/18.jpg)
Statistical analysis Statistical analysis
SPSS 17.0 software programKolmogorov-Smirnov Z-testNonparametric testsMann–Whitney test for 2 independent samples (Monte Carlo method) between groups comparisonsWilcoxon test for 2 related samples, within group comparisons
Bonferonni correction was used in order to make our significance criterion more conservative
SPSS 17.0 software programKolmogorov-Smirnov Z-testNonparametric testsMann–Whitney test for 2 independent samples (Monte Carlo method) between groups comparisonsWilcoxon test for 2 related samples, within group comparisons
Bonferonni correction was used in order to make our significance criterion more conservative
![Page 19: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/19.jpg)
Study ResultsStudy Results
![Page 20: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/20.jpg)
Between groups comparison
Between groups comparison
Experimental group in comparison to controls had better performance
in:
attention (p= .009)
visual memory (p= .043)
executive function (p≤ .000)
Experimental group in comparison to controls had better performance
in:
attention (p= .009)
visual memory (p= .043)
executive function (p≤ .000)
At the end of the intervention
(2 years period)
At the end of the intervention
(2 years period)
![Page 21: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/21.jpg)
Ability Control Group *M (SD) (N=45) Experimental Group *M (SD) (N=95) p
Global cognitive function (Total MoCA) 23.64 (4.04) 24.29 (3.66) NS
ADL (Total FRSSD) 3.83 (2.02) 3.38 (1.42) NS
ADL (Total FUCAS) 43.71 (1.99) 43.14 (1.39) NS
ATTENTION
Inhibition interference (STROOP) -5.78 (9.00) -1.86 (7.40) NS
Digit symbol (WAIS - R) 29.36 (13.17) 30.43 (10.35) NS
Auditory sustained attention (MoCA) .82 (.38) .97 (.16) .009
VERBAL MEMORY
Learning ability (RAVLT) 10.97 (2.53) 11.30 (2.74) NS
Delayed recall (RAVLT) 8.27 (3.21) 11.30 (2.74) NS
Immediate story recall (RBMT) 12.23 (3.25) 13.12 (3.14) NS
Delayed story recall (RBMT) 11.42 (3.75) 12.40 (3.29) NS
VISUAL MEMORY 29.01 (6.29) 30.50 (4.54)
Complex figure delayed recall (ROCFT) 13.40 (6.86) 15.92 (7.00) .043
VISUAL CONSTRUCTIVE ABILITIES
Complex figure copy (ROCFT) 29.01 (6.29) 30.50 (4.54) NS
LANGUAGE
Naming without help (per cent %) (BNT) 79.65 (16.10) 78.88 (14.70) NS
EXECUTIVE FUNCTION
Phonemic verbal fluency (FAS) 9.82 (2.49) 11.95 (3.41) .000
Trail making part B (TRAIL B) 249.68 (138.18) 204.06 (96.45) NS
Planning (FUCAS) 6.20 (.45) 6.03 (.17) .004
Working memory (MoCA) 2.53 (.75) 2.81 (.42) NS
![Page 22: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/22.jpg)
Within Group Comparisons between the 1st and the 2nd
assessment
Within Group Comparisons between the 1st and the 2nd
assessment
abilities of attention (p≤ .002) executive function (p≤ .008) verbal memory (p≤ .003) visual memory (p= .000)language (p= .000)
global cognitive performance (p= .028)
abilities of attention (p≤ .002) executive function (p≤ .008) verbal memory (p≤ .003) visual memory (p= .000)language (p= .000)
global cognitive performance (p= .028)
Experimental group
After two years’ participation in cognitive training
Experimental group
After two years’ participation in cognitive training
Has shown improvement in:
![Page 23: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/23.jpg)
Ability Μ(SD)* 1st Assessment M (SD)* 2nd Assessment p
Global cognitive function (Total MoCA) 23.05 (2.79) 24.29 (3.66) .000
ADL (Total FRSSD) 3.83 (1.92) 3.38 (1.42) NS
ADL (Total FUCAS) 43.34 (1.33) 43.14 (1.39) NS
ATTENTION
Visual selective attention (TEA) 27.83 (10.07) 30.30 (9.53) .001
Speed of selective attention (multiple choices) (TEA) 5.16 (2.05) 4.81 (1.39) .003
Inhibition interference (STROOP) -4.57 (7.04) -1.86 (7.40) .002
Digit symbol (WAIS - R) 28.10 (9.50) 30.43 (10.35) .001
Auditory sustained attention (MoCA) .93 (.25) .97 (.16) NS
Digit span (RAVLT) 4.94 (2.07) 5.72 (2.22) .002
VERBAL MEMORY
Learning ability (RAVLT) 10.59 (2.75) 11.30 (2.74) .003
Delayed recall (RAVLT) 7.14 (3.56) 11.30 (2.74) .000
Immediate story recall (RBMT) 13.10 (3.18) 13.12 (3.14) NS
Delayed story recall (RBMT) 12.15 (3.57) 12.40 (3.29) NS
VISUAL MEMORY
Complex figure delayed recall (ROCFT) 12.11 (6.04) 15.92 (7.00) .000
VISUAL CONSTRUCTIVE ABILITIES
Complex figure copy (ROCFT) 29.71 (4.64) 30.50 (4.54) NS
LANGUAGE
Naming without help (per cent %) (BNT) 71.95 (15.14) 78.88 (14.70) .000
EXECUTIVE FUNCTION
Numbers of trials attempted (WCST) 91.97 (20.50) 88.61 (16.94) .005
Perseverative responses (WCST) 11.65 (8.81) 9.32 (6.38) .001
Phonemic verbal fluency (FAS) 9.57 (2.70) 11.95 (3.41) .000
Trail making part B (TRAIL B) 229.79 (97.17) 204.06 (96.45) .002
Planning (FUCAS) 6.03 (.17) 6.03 (.17) NS
Working memory (MoCA) 2.80 (.45) 2.81 (.42) NS
![Page 24: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/24.jpg)
Within Group Comparisons between the 1st and the 2nd
assessment
Within Group Comparisons between the 1st and the 2nd
assessment
Significant improvement in:
visual memory (p= .006)attention (p= .007)
Significant deterioration in: executive function (p≤ .006)
The rest of the cognitive abilities remained stable
Significant improvement in:
visual memory (p= .006)attention (p= .007)
Significant deterioration in: executive function (p≤ .006)
The rest of the cognitive abilities remained stable
After two years
control group
has shown:
After two years
control group
has shown:
![Page 25: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/25.jpg)
Ability Μ(SD)* 1st Assessment M (SD)* 2nd Assessment p
Global cognitive function (Total MoCA) 23.23 (2.84) 23.64 (4.04) NS
ADL (Total FRSSD) 4.33 (1.73) 3.83 (2.02) NS
ADL (Total FUCAS) 43.00 (1.34) 43.71 (1.99) NS
ATTENTION
Inhibition interference (STROOP) -3.98 (10.56) -5.78 (9.00) NS
Digit symbol (WAIS - R) 27.61 (11.51) 29.36 (13.17) NS
Auditory sustained attention (MoCA) .94 (.22) .82 (.38) NS
Digit span (RAVLT) 4.20 (1.50) 4.92 (2.10) .007
VERBAL MEMORY
Learning ability (RAVLT) 10.84 (2.28) 10.97 (2.53) NS
Delayed recall (RAVLT) 8.15 (3.23) 8.27 (3.21) NS
Immediate story recall (RBMT) 12.82 (3.33) 12.23 (3.25) NS
Delayed story recall (RBMT) 12.20 (3.25) 11.42 (3.75) NS
VISUAL MEMORY
Complex figure delayed recall (ROCFT) 11.31 (4.76) 13.40 (6.86) .006
VISUAL CONSTRUCTIVE ABILITIES
Complex figure copy (ROCFT) 29.64 (5.29) 29.01 (6.29) NS
LANGUAGE
Naming without help (per cent %) (BNT) 69.69 (14.17) 79.65 (16.10) NS
EXECUTIVE FUNCTION
Phonemic verbal fluency (FAS) 9.46 (2.13) 9.82 (2.49) NS
Trail making part B (TRAIL B) 205.29 (102.62) 249.68 (138.18) .000
Planning (FUCAS) 6.02 (.15) 6.20 (.45) NS
Working memory (MoCA) 2.86 (.34) 2.53 (.75) .006
![Page 26: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/26.jpg)
Conversion to dementia
Conversion to dementia
6 patients (13.33%) out of the controls converted to dementia, as they fulfilled the dysfunction criteria for dementia (performance in FUCAS’ ADL ≥ 47)
NONE of the experimental group converted to dementia after two years of participation in cognitive training
6 patients (13.33%) out of the controls converted to dementia, as they fulfilled the dysfunction criteria for dementia (performance in FUCAS’ ADL ≥ 47)
NONE of the experimental group converted to dementia after two years of participation in cognitive training
![Page 27: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/27.jpg)
Conclusions Conclusions
![Page 28: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/28.jpg)
Cognitive training helped experimental patients to: Cognitive training helped experimental patients to:
Improve abilities of attention and executive functionGeneralize the cognitive benefit in visual memory, language & verbal memoryStabilize ADL Minimize the rate of conversion to dementia
Improve abilities of attention and executive functionGeneralize the cognitive benefit in visual memory, language & verbal memoryStabilize ADL Minimize the rate of conversion to dementia
![Page 29: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/29.jpg)
Further studies are needed in order to examine the longitudinal effectiveness of cognitive training in MCI
Further studies are needed in order to examine the longitudinal effectiveness of cognitive training in MCI
![Page 30: Alzheimer Hellas 3rd Department of Neurology, Medical School,](https://reader035.vdocument.in/reader035/viewer/2022062221/56813949550346895da0e86f/html5/thumbnails/30.jpg)
Thank youThank you
Contact e-mail: [email protected]@alzheimer-hellas.gr
Contact e-mail: [email protected]@alzheimer-hellas.gr
for your attentio
n