mild cognitive impairment - geriatrie.be...the diagnosis of mild cognitive impairment due to...
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De Cock anne-MarieUniversitaire dienst. geriatrie,
ZNA middelheim, Antwerpen Vakgroep ELIZA UA ,
Universiteit ANtwerpen
Mild Cognitive Impairment
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Dementia is a continuum
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Clinical Characterization of MCI
Petersen Criteria:
• 1. Memory Complaint
• 2. Normal Activities of Daily Living (ADLs)
• 3. Normal General Cognitive Function
• 4. Abnormal Memory for Age
• 5. Not Demented
• (Petersen et al 1999)
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What’s in a NAME 1999-2016
• CIND ( cognitive impairment no dementia) = most closely related to MCI (1997)
• MCI ( Petersen - 1999) (NIA-AA criteria 2011)
• AAMI / AACD = is normal ageing
• is identified as state of impairment similar to MCI (1999)
• Preclinical AD ( 2011 NIA-AA criteria) : no MCI – biomarkers positive
• DSM-V= Mild neurocognitive disorders = is overall MCI definition. (2013)
• Suspected non-AD pathology (SNAP) MCI = meet criteria for MCI – no biomarkers (2015)
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2011 NIA-AA
• 1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2011 May;7(3):280-92. PubMed PMID: 21514248. Pubmed Central PMCID: 3220946.
• 2. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2011 May;7(3):270-9. PubMed PMID: 21514249. Pubmed Central PMCID: 3312027.
• Pre-clinical stages of AD
• MCI due to AD
• AD
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NIA-AA
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NIA-AA
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Subjective memory complaints Jessen 2014
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Memory clinic
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EVALUATION
• 1. severity
• 2. follow-up
• 3. pro active decision making
• 4. detection of treatable conditions
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Diagnosis
• A. In office
• Interview (ADL , IADL, AADL, Social )
• Cognitive screening (MMSE , MOCA , Addenbrooks Revised)
• Medical and neurological examination
• Psychiatric conditions
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• MMSE
• Clock drawing test
• MOCA
• Addenbrooks cognitive evaluation – revised
• Neuropsychological testing (NPT)
TESTINg
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• B. NPT CDR
CDR code
CDR 0.5 + MMSE > 24 = MCI
CDR 0 30% of them is MCI
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Normal MCI AD
CDR 0.5
GDS
2 3
Mild Cognitive ImpairmentCDR and GDS
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• C. Neuro imaging
• CT scan
• MRI
• PET scan
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MRI
WML
Microbleeds
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• MRI /CT
• FDG-PET
• Amyloid-PET
• Tau-PET
MCI imaging
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Diagnosis
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Progression Risk MCI to AD
• 10% per year
• Older age.
• Fewer years of education.
• Multidomain amnestic MCI.
• Life-style
• High fat diet.
• Excessive alcohol intake
• Stressful lifestyle
• Medical comorbidities:
• Metabolic syndrome
• Chronic inflammatory diseases
• Vascular disease
• Thyroid disorders
• Elevated homocysteine levels
• Psychological features : Untreated depression.
• Gait speed
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Quantitative gait analysis
Falls risk
Attention reserves
MCI -5 years before dementia
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Pre MCI Motor changes
Gait speed Finger tapping
Buracchio T, Dodge HH, Howieson D, Wasserman D, Kaye J. The trajectory of gait speed preceding mild cognitive impairment. Arch Neurol. 2010;67:980–986.
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Criteria for MCR JGMS 2012 Verghese et al.
Participants met all four criteria :
1. Cognitive complaints were assessed questionnaire, Study clinicians’ observations during clinical interviews or informant reports
2. Slow gait as gait speed one standard deviation (SD ) or more below age- and sex-appropriate mean values established in the same cohort (reference ).
3. Preserved activities of daily living assessed by a scale developed for assessing function in community-residing older adults (19 ) as well as study clinicians’ interviews.
4. Absence of dementia ( in study by follow up mean 36 months)
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Motoric Cognitive Risk Syndrome and the Risk of Dementia
Joe Verghese,et al.
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Motoric cognitive risk syndrome : multicountry prevalence and dementia risk.J. Verghese et al . 2014 Neurology 83.
• 10 %
Pooled Prevalence of MCR
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MCR and risk of incidence
• Cognitive impairment
• Dementia
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Incidence MCR by age
Motoric cognitive risk syndrome : multicountry prevalence and dementia risk.J. Verghese et al . 2014 Neurology 83.
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GOOD Consortium
Title: Poor gait performances and prediction of dementia: results from a meta-analysis.
Authors’ names and surnames: Olivier Beauchet, MD, PhD1; Cédric Annweiler, MD, PhD2; Michele L Callisaya, PhD3,4; Anne-Marie De Cock, MD5; Jorunn L. Helbostad, PhD6; Reto W. Kressig, MD7 ;Velandai Srikanth, PhD4; Jean-Paul Steinmetz, PhD8; Helena M. Blumen, PhD9, Joe Verghese, MD, MBBS9; Gilles Allali, MD, PhD10
JAMDA, February 2016
Review and meta-analysis
Dementia Pooled Hazar ratio P-Value
All dementia’s 1.53 <0.001
Vascular Dementia 1.79 <0.001
Non-Alzheimer dementia 1,89 <0.001
Alzheimer dementia 1,03 0.004
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GOOD project
0200400600800100012001400051015202530Mean value Coefficient of variation Stride length Stride time Swing time Stance time Single support Double support Stride width Stride velocity % P<0.001 P<0.001 P<0.001 P=0.254 P=0.278 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.111 P<0.001 P<0.001 P<0.001 P<0.001 CHI A-MCI NA-MCI Mild dementia AD Mild dementia non-AD Moderate dementia AD Moderate dementia non-AD
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GOOD project
0200400600800100012001400051015202530Mean value Coefficient of variation Stride length Stride time Swing time Stance time Single support Double support Stride width Stride velocity % P<0.001 P<0.001 P<0.001 P=0.254 P=0.278 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.111 P<0.001 P<0.001 P<0.001 P<0.001 CHI A-MCI NA-MCI Mild dementia AD Mild dementia non-AD Moderate dementia AD Moderate dementia non-AD
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Fig 3. Multivariable logistic regression Models 1 and 2.
De Cock AM, Fransen E, Perkisas S, Verhoeven V, Beauchet O, et al. (2017) Gait characteristics under different walking conditions: Association with the presence of cognitive impairment in community-dwelling older people. PLOS ONE 12(6): e0178566. https://doi.org/10.1371/journal.pone.0178566http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178566
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Not recommended or no standarization for predicting progression in MCI
• Presence of apolipoprotein E (ApoE) E4 allele.
• Magnetic resonance imaging (MRI), with volumetric measurements of the hippocampus at or below the 25th percentile for matched age and sex.
• Cerebrospinal fluid biomarkers
• Neuropsychological test measures
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Pharmalogical Treatment
• Acetylcholinesterase Inhibitors:
• favored donepezil at 1 year but not at 3 years follow-up. ( a MCI +ApoE4-positive individuals)
• Memantine:
• not been reported to benefit patients with MCI.
• Piribedil:
• dopamine receptor agonist, having acetylcholine release in the hippocampus and the frontal cortex as a putative mechanism of action. Pirbidel improved cognition over 3 months on the primary outcome in placebo-controlled study by Nagraj et al. in National Institute of Mental Health and Neurosciences (NIMHANS).
• Nicotine:
• Brain nicotinic receptors are important for cognitive function. Nicotine patches improved attention, but not global functioning, over 6 months
• Cyclooxygenase (COX)-2 inhibitors:
• Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce brain neurotoxic inflammatory responses and so was assumed to improve cognition.
• Rofecoxib increased incident cases of Alzheimers dementia in the study and has a fair evidence against its use. [
• Trifusal (COX-1 and COX-2 inhibitors) had no effect on cognition but was associated with a reduced risk of conversion to AD
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Pharmacological Treatment
• Gingko biloba:
• increasing brain the blood supply, modifying neurotransmitter systems, and reducing oxygen-free ra dical density. Results +/-
• Vitamin B:
• Higher homocysteine plasma concentrations are decreased by B vitamins. Immediate memory - attention and executive functioning +/-
• Antioxidants such as vitamin E, vitamin C, and curcumin (from turmeric)
• reduce oxidative stress and ageing, yet work in this field is largely in the incipient stages.
• Omega-3 polyunsaturated fatty acids (PUFAs):
• verbal fluency and depressive symptoms at 6 months follow-up +
• Antiamyloid therapies:
• under research, along with the vaccines that would prevent amyloid plaque formation. ( preliminary -
• Neurotonics:
• piracetam -
• Estrogens:
• the risk for MCI and AD
• Huannao Yicong responded on a cognition and social functioning measure but the result –
• CDP choline, calcium channel blocker nimodipine and testosterone supplementation seem partially effective.
• Drugs on trial for MCI include vasoactive intestinal peptide (AL-208), a selective metabotropic glutamate receptor antagonist (C-105), a novel L-type calcium channel blocker (MEM- 1003), a phosphodiesterase inhibitor (MEM-1414), a gamma-aminobutyric acid B receptor antagonist (SGS-742), and a selective serotonin receptor (5HT6) antagonist (SGS-518). [
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Non-pharmacological Treatment
• Treatment comorbidities
• vascular ,such as hypertension, diabetes, atrial fibrillation, obesity, vitamin deficiency, hypothyroidism, depression, and sleep disturbances.
• Abstention from heavy alcohol, smoking, and other substances of abuse
• Establishment of a fixed and disciplined routine.
• Diet: A Mediterranean diet + Second dietary curcumin
• Socialization with people, being part of a senior citizen's group, etc.
• Spiritual activity.
• Physical exercise/activity
• Inconsistent results of improvement in fluency, memory, and trail-
• any frequency of moderate exercise reduced odds of having MCI
• Computer-assisted cognitive training:
• objective and subjective measures of memory, quality of life, and mood
• Cognitive stimulation:
• increase cognitive and social functioning in a nonspecific manner. Decreased risk of cognitive decline, amnestic MCI and AD
• Family psychological intervention:
• memory improvement up to 4 months later in a trial that was not placebo-controlled.
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THM
• MCI is not only a precursor for AD
• Diagnosis in a rigorous system of evaluation
• Predicting progression to AD is possible
• Treatment is still lacking – regular follow-up (6-12)
• Prevention and detection of treatable conditions
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