Lecture 5: Mild Cognitive Impairment & Subjective Cognitive Decline Flashcards
Mild Cognitive Impairment & Subjective Cognitive Decline:
- Which is considered part of normal ageing and which is considered part of abnormal ageing?
Mild Cognitive Impairment: part of abnormal cognitive ageing Subjective Cognitive Decline: part of normal ageing
Overview of possible cognitive age-related concerns:
Subjective Cognitive Decline
SCD (Jessen er al. 2014) :
- Older adults complain about perceived decline in cognitive abilities
- Within normal limits standard neuropsychological or other clinical measures
- No impairments IADL (Instruments Activity of Daily Living)
Criteria for diagnosis (for SCD):
- Decline relative to prior levels (subjective decline)
- Decline not due to psychiatric or other conditions, medicattion, substance use (reversable causes)
(for a long time they were referred to as the “worried well” and it was thought that there is nothing wrong with them)
Subjective Cognitive Decline (consequences)
- increased risk developing MCI and AD
- Rates vary: 5 – 50%
- Meta-analysis (Mitchell et al., 2014):
- adults SCD twice as likely (10.9%) to develop dementia than without SCD over 4 year period
- Higher frequencies AD biomarkers (“SCD plus”)
- Volume loss hippocampus, medial temporal areas
- Amyloid plaques
- Evidence mixed
- in SCD “plus” the “plus” refers to the presence of biomarkers
Differential diagnosis (SCD vs MCI or dementia):
- Formal neuropsychological assessment (simple because SCD is - contrary to MCI and dementia - defined as being in the limits of normal ageing by neuropsychological assessments)
Differential diagnosis, SCD vs normal ageing:
- Lack objective measures SCD (can’t use neuropsychological tests)
- Differentiation based on self report
- No SCD typical complaint of cogntive domain
- Concern/worry more sensitive as indicator SCD
- Increased risk conversion dementia
- Other etiologies (e.g. depression, chronic medical conditions)
Mild cognitive impairment (MCI):
- decline in cognitive performance greater than expected from person’s age, not sufficient to warrant diagnosis dementia.
- MCI is stage between normal cognition and dementia
- MCI: pathological condition, not part of normal ageing
- MCI: stage between normal cognition and dementia in terms of severity and progression
- however, it does not necessarily lead to dementia, some also return to normal functioning
Mild cognitive impairment, Diagnosis.
Original criteria Petersen (1999), Mayo criteria:
Original criteria Petersen (1999), Mayo criteria:
- subjective complaint memory impairment
- objective evidence of memory deficit (disctinction to SCD)
- 1.5. SD below norm on 20 min. delayed recall story A of WMS Logical Memory task
- overall cognitive functions preserved (MMSE >= 24)
- intact activities of daily life (global Clinical Dementia Rating (CDR) scale of 0.5)
- absence of dementia (consensus diagnosis)
These criteria were strict and limited to memory.
Mild cognitive impairment, Revised criteria for Diagnosis.
NIA-Alz Association task force for MCI (Albert et al. 2011):
- Concern about change in cognition.
- Change larger than expected from person’s age, education
- Evidence impairment one or more cognitive domains
- no longer memory only
- 1 - 2 SDs below mean
- Preservation independence in daily functioning
- or only mild difficulties
- Not demented
- impairments and mild difficulties IADL not severe enough interfere with social or occupational functioning
- MCI as diagnosis (associated with dementia pathology)
- Not description of current functioning
- MCI is a condition\diagnosis based on functioning but not just a description of the degree of functioning
- Overlap criteria for minor neurocognitive impairment DSM 5.
- DSM also requires that changes not due to delirium or Axis 1 disorders (depression, schizophrenia).
Mild cognitive impairment, Revised criteria.
Overlap with other diagnoses or pathologies:
- Overlap criteria for minor neurocognitive impairment DSM 5.
- DSM also requires that changes not due to delirium or Axis 1 disorders (depression, schizophrenia).
- Overlap “cognitive impairment no dementia”(CIND)
- Label first used in Canadian epidemiological studies
- CIND – any cognitive disorder (not only memory) from various possible causes, including drug use, alcohol abuse, psychiatric illness, degenerative illness.
- MCI more specific than CIND
Mild cognitive impairment, revised criteria.
Various causes for cognitive impairment:
- Some causes may be reversible
- Persons diagnosed with MCI can revert to normal function
- depending on what the cause is MCI might be reversible to normal functioning or not
Mild cognitive impairment.
Petersen (2004): 4 main etiologies for MCI:
- Degenerative (e.g. AD)
- Vascular (e.g. cerebrovascular disease)
- Psychiatric (e.g. depression)
- Traumatic (e.g. head injury)
Other causes are possible (e.g. drug effects, thyroid dysfunction, B12 deficiency).
- 1 & 2: MCI possibly pre-stage of dementia
- but if due to 3. or 4. (psychiatric or traumatic reasons) it is well ossible that a person returns to normal functioning after the cause is treated/healed.
Types of MCI
- Depending on cognitive domains affected
- amnestic MCI (aMCI) – memory impaired, other domains spared
- nonamnestic MCI (naMCI) – memory spared, other domains impaired (e.g. executive function, language),
- Single domain or multiple domains (distinction)
- One (SD - single domain) or more than one cognitive domain/function (MD - multiple domain) impaired.
Cognitive impairments in MCI
Example study about Memory
(Rabin et al., 2009)
MCI group, impaired on range of verbal and visual memory tests – aMCI
- notice that on all different memory tasks the MCI group performs worse than healthy controls
Cognitive impairments in MCI
Example study of memory and other cognitive functions.
(Grundman et al., 2004)
MCI group impaired on memory, EF, speed and language tests
- multiple functions can be impaired
Cognitive impairments in MCI
Example study: single or multiple domains
(Brandt et al., 2009)
- some of subgroups are only impaired on a single domain (e.g. memory)
- others don’t have imapirments of memory but on different other domains (EF, etc.)
Prevalence of MCI
- Uncertainty prevalence MCI
- Wide variation between studies (3% - 54%)
- partly due to diagnostic methods used and populations sampled
Reasons for different estimates of the prevalence of MCI:
- populations sampled:
* Prevalence higher in clinical samples (persons with memory or other cognitive complaints) than in population samples - different diagnostic criteria used
- Criteria to define impairments more strict – lower prevalence
- Criteria to define impairments less strict – higher prevalence
- different diagnostic methods used
- More cognitive domains assessed, more sensitive tests:
- more likely to find cognitive impairments due to chance (higher prevalence MCI)
Prevalence of MCI regarding age and gender
From: Petersen et al (2010)
- increases with age
- higher in men
Prevalence of MCI regarding education:
From: Petersen et al (2010)
- lower prevalence with more years of education
- true among men and women
Prevalence of MCI regarding amnestic vs non-amnestic MCI and Single vs. multiple domain categories:
From: Petersen et al (2010)
- MCI with memory impairments most prevalent
- Prevalence amnestic MCI higher than non-amnestic MCI (SD and MD).
- least prevalent is the non-amnestic, multi-domain MCI
Brain changes in MCI
- Structural - volume
Jack et al. (2000)
- Volume hippocampus in MCI (amnestic MCI) < healthy older adults > AD
- 2 – 4 year follow-up: more reduction volume hippocampus MCI than healthy older adults
- less reduction than in AD (but NS)
- 2 – 4 year follow-up: less reduction volume hippocampus in MCI who maintained baseline cognitive performance (MMSE, Dementia Ratings Scale) than decliners
So, rate of reduction in volume was higher in MCI group compared to control but lower compared to AD group.
Mild cognitive impairment
Areas of volume loss (cortical thinning) of MCI groups relative to HC group:
(Chang et al., 2010)
- most volume loss in temporal and frontal areas
Structural brain changes
Chang et al. (2010):
Conversion rate to AD over 2 years:
- Conversion rate to AD over 2 years:
- higher in MCI groups than HC groups
- highest in most impaired group – LL LR (low on learning & low on retention)
So, MCI is a risk factor for developing AD
Mild cognitive impairment
Functional brain changes:
- Less activation medial temporal lobe during memory task in MCI than healthy older adults
- same area were the hippocmpus lies and where AD patients have particularly high atrophy
- No difference activation MCI or AD (Machulda et al., 2003)
¨Mild cognitive impairment
Functional brain changes (more activation)
(Dickerson et al., 2004)
- More activation hippocampal formation and parahippocampal gyrus - better memory performance in MCI (Dickerson et al., 2004)
- Follow-up 2.5 years: 14 persons with MCI declined on CDR (general cognition), 18 remained at baseline level
- so, those that performed better in memory had more activation
- Decliners (those of MCI that showed decline in overall cognitive function) – more activation parahippocampal gyrus than stable persons during memory task
- No group difference performance memory task
- Increased activation despite same level of memory performance. What could this mean?
- maybe it is a form of compensation
Neuropathology in MCI.
From: Schneider et al., 2009
Neuropathology in MCI
- 400 postmortem examinations
- around 25% had no detectable abnormalities associated with forms of dementia
From: Schneider et al., 2009.
134 MCI diagnosis
- Postmortem 73 persons with AD pathology:
- 44 (59%) diagnosis amnestic MCI
- 29 (49%) diagnosis nonamnestic MCI
Range in conversion rate can result from :
- Population from which sample is drawn
- from general older population:
- more likely MCI cases come from normal population, lower conversion rate
- 16% of normal population will score below 1 SD from mean on a cognitive test
- from group with clinical concerns (e.g. recruited at memory clinics)
- more likely MCI cases come from “predementia” population, higher conversion rate
Conversion to dementia (MCI to Dementia).
Return to normal:
Alexopolous et al. (2006)
Pandya et al. (2016)
Majority of persons with MCI do not progress to dementia
- Return to normal or remain stable
- Alexopolous et al. (2006), 41% of persons with MCI remained stable over 3.5 years and 17% returned to normal functioning
- Pandya et al. (2016): review reversion rate 20-50% returned to normal cognition
Conversion to dementia
Difference conversion rate aMCI and naMCI:
Gauthier et al. (2006). consensus from 2005 expert conference on MCI.
- persons with aMCI more likely to convert to AD than persons with naMCI
- MCI affecting multiple domains more likely to convert to dementia
- Especially if memory was one of domains affected (Loewenstein (2013) in: Handbook Neuropsychology of Aging and Dementia)
- MD aMCI more likely to progress to dementia than SD aMCI (Michaud et al., 2017)
- Persons with naMCI higher risk for other forms dementia (Lewy bodies, frontotemporal dementia) than for AD
Difference between amnestic MCI and non-amnestic MCI in frequency of AD, Lewy body and vascular pathology .
134 MCI diagnosis
Little difference between amnestic MCI and non-amnestic MCI in frequency of AD, Lewy body and vascular pathology .
From: Schneider et al., 2009
Assessment of MCI
- Differential diagnosis:
- symptoms of MCI can be caused by various disorders
- not necessarily dementia/some causes may be reversible
- identify etiology of cognitive impairment
