Mild cognitive impairment A view on grey areas of a grey area diagnosis
Dr Sergi Costafreda Senior Lecturer
Division of Psychiatry, UCL
Islington Memory Service, C&I NHS FT
London Dementia Strategic Clinical Network 14/06/2017
A grey area: does the label MCI benefit patients?
- Harms of diagnosis
- There is no cure so aren’t we just worrying people unnecessarily?
- Can’t we just reassure and leave?
- There is evidence of significant clinical variability in the use of the MCI label
Petersen 2004 A research diagnosis
The grey zone is between healthy cognitive ageing and dementia (mainly AD)
Resnick et al, Neurology 2010;74:807–815
The grey zone is between healthy cognitive ageing and dementia (mainly AD)
Resnick et al, Neurology 2010;74:807–815
Continuum normal ageing to dementia: MCI is the grey area
MCI responds to a grey zone
This development
was stimulated first by the clinical awareness
of the existence of a grey zone of cognitive impairment
that was not captured by any clinical definition
and by the rising awareness of dementia as an
important area of public health. Further, it was
reinforced by the emerging clinical need of something
beyond the binary diagnosis of the presence or
absence of dementia, which could allow an earlier
diagnosis and secondary prevention if new treatments
were proved efficacious at these early stages
The concept has moved
rapidly outside the research field providing clinicians
with a helpful intermediate diagnosis, often
for watchful waiting.
(Petersen et al, 2014)
Extremely prevalent with high risk of dementia
MCI as a clinical diagnosis Benefits: yes for research
Benefits for individual patient?
Benefits at a social level?
Benefits of MCI diagnosis
An early diagnosis is crucial for counseling, for planning treatment and care, and for advance directives.
Scientifically, the possibility of making an early (predementia) diagnosis is essential for the clinical
evaluation of novel, potentially disease-modifying drugs against AD.
Benefits of MCI diagnosis
Serious harm from diagnosis: suicide
• mistrust clinical experience: Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment
CONCLUSION: Disclosure of a dementia diagnosis does not prompt a catastrophic emotional reaction in
most people, even those who are only mildly impaired, and may provide some relief once an explanation for
symptoms is known and a treatment plan is developed. Brian D. Carpenter et al. 2008. Journal Am Geriatr Assoc.
(But N=90)
• In population studies (N~100K to 2M):
Suicide in dementia is relatively rare (1-2 per thousand), no real info for mild cognitive impairment
Suicide in dementia is x3 (LOD) to x10 (EOD) times more likely than in healthy elderly people.
Cognitive impairment likely a risk factor in elderly suicide (even if no dementia diagnosis)
The EO dementia is very high. The rate for LOD is similar to brain cancer, g-i cancer, liver diseases.
Risks factor include depression, psychiatric history, antidepressant/anxiolytic treatment. The highest
risk is first 3 months of diagnosis but elevated risk continues beyond that.
(Seifreid et al, 2011, Alz & Dem; Erlangsen et al, 2008 Am J Geriatr Psychiatry)
Subjective memory concerns Results: Correlational and regression analyses indicated that subjective memory complaints
displayed a poor relationship with objective memory performance. A subsequent discriminant
function analysis indicated that subjective memory complaints failed to improve the
diagnostic accuracy of MCI and resulted in increased rates of false negative and false
positive diagnoses.
Conclusion: The results of the present study suggest that a diagnostic criterion of subjective
memory complaint reduces the accuracy of MCI diagnosis, resulting in an elevated rate of false
positive and false negative diagnoses. The results of this study in conjunction with recent
research indicate that a criterion of subjective memory complaint should be discarded
from emerging diagnostic criteria for MCI.
Lenehan et al. International Psychogeriatrics. 2012, 9:12 pp. 1505-1514
Subjective memory concerns Results: Correlational and regression analyses indicated that subjective memory complaints
displayed a poor relationship with objective memory performance. A subsequent discriminant
function analysis indicated that subjective memory complaints failed to improve the
diagnostic accuracy of MCI and resulted in increased rates of false negative and false
positive diagnoses.
Conclusion: The results of the present study suggest that a diagnostic criterion of subjective
memory complaint reduces the accuracy of MCI diagnosis, resulting in an elevated rate of false
positive and false negative diagnoses. The results of this study in conjunction with recent
research indicate that a criterion of subjective memory complaint should be discarded
from emerging diagnostic criteria for MCI.
Lenehan et al. International Psychogeriatrics. 2012, 9:12 pp. 1505-1514
Perhaps this makes sense in research, but does it clinically?
The Nuffield Trust for bioethics report on dementia
- After considering benefits/risks
of diagnosis
“People should have access to
good quality assessment and
support from the time they, or their
families, become concerned
about symptoms of dementia”
- This is for dementia, but in my
view applies to MCI as well
Criteria and grey areas in clinical definition
• Depends on patient/informant report
(?insight)
• Preserved independence in functional
abilities/ preserved general functional
abilities: no hard boundary
• No prescribed tests/cut-offs: variability in
practice (?ACE-R 90, other tests?)
• No presence of neuropsychiatric
symptoms in criteria but frequent subtle
changes such as increased reactivity to
stress
Vega & Newhouse. Curr Psychiatry Rep. 2014 Oct; 16(10): 490.
Preserved functional independence: the grey area at
the centre of a grey area diagnosis
“Very mild problems in instrumental ADL
are generally consistent with MCI, whilst basic
ADL should be preserved.”
Petersen 2014
There is a gap here!
- Does abandonment of high-end activities
count as significant functional impairment?
- Does abandonment of driving, or driving only
in local areas, count as significant functional
impairment?
- Does getting some help with finances count
as significant functional impairment?
Room for subjectivity
Back in the real world CT brain scan was …
MCI: syndromic versus aetiological diagnosis
The syndromic diagnosis
• MCI vs normal vs dementia
• aMCI vs multidomain MCI vs naMCI
The aetiological diagnosis
The subsequent aetiological categories
include AD, frontotemporal dementia,
vascular cognitive impairment, dementia with
Lewy bodies, Parkinson’s disease,
Huntington’s disease, HIV/AIDS, traumatic
brain injury and substance abuse
Back in the real world CT brain scan was within normal limits for age
What do we do?
Back in the real world CT brain scan showed global involutional changes
without lobar predilection within normal limits for age,
and small vessel disease.
What do we do?
Back in the real world CT brain scan was within normal limits
What do we do? A. Discharge with advice
B. Advice and review in 1 year
C. Neuropsychology
D. More scans / other tests
What advice?
Findings The prevalence of MCI in adults aged 65 years and older is 10% to 20%; risk increases with age and
men appear to be at higher risk than women.
• In older patients with MCI, clinicians should consider depression, polypharmacy, and uncontrolled
cardiovascular risk factors, all of which may increase risk for cognitive impairment and other negative
outcomes.
Currently,
• no medications have proven effective for MCI;
• treatments and interventions should be aimed at reducing cardiovascular risk factors and prevention
of stroke.
• Aerobic exercise, mental activity, and social engagement may help decrease risk of further cognitive
decline.
Grey areas: Follow-up
• Should we follow?
• Actively recall vs patient/GP to re-refer?
• When to recall? 6 months-1year?
• What do we do at meeting?
• Any cognitive and functional changes?
• Cognitive testing?
• When to re-scan?
Grey areas: Follow-up
• Should we follow?
• Actively recall vs patient/GP to re-refer?
• When to recall? 6 months-1year?
• What do we do at meeting?
• Any cognitive and functional changes?
• Cognitive testing?
• When to re-scan?
2010 Neurologists survey in US on MCI When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%)
and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of
findings (15%).
Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other
agents (e.g., vitamin E) prescribed less frequently.
Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2)
motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%).
Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer
disease (21%); and 3) diagnosis can cause unnecessary worry (20%).
2010 Neurologists survey in US on MCI When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%)
and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of
findings (15%).
Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other
agents (e.g., vitamin E) prescribed less frequently.
Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2)
motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%).
Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer
disease (21%); and 3) diagnosis can cause unnecessary worry (20%).
Grey area: depression and memory Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker
for future cognitive impairment (aMCI)
http://www.sciencedirect.com/science/article/pii/S1064748116302408
So should we treat depression to prevent
dementia?
Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer’s disease
(1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies,
showed that the risk of vascular dementia was significantly higher than for Alzheimer’s disease (P = 0.03).
http://bjp.rcpsych.org/content/202/5/329.short
Baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7; 95% CI, 1.2-2.3)
but not with incident MCI (0.9; 0.7-1.2). Persons with MCI and coexisting depression at baseline had a higher risk of
progression to dementia (HR, 2.0; 95% CI, 1.2-3.4), especially vascular dementia (4.3; 1.1-17.0), but not Alzheimer disease
(1.9; 1.0-3.6). http://jamanetwork.com/journals/jamaneurology/fullarticle/1542838
Assessing Patients with Late-Life Depression for MCI
Depressive symptoms have been found to occur in up to 63% of individuals with MCI [41]. Although depression and is frequently
associated with MCI and dementia [42–48], the role of depression as a risk factor for MCI and dementia is not fully understood.
Differentiation between cause and effect is particularly challenging when assessing patients with late-life depression for MCI since
depression by itself is associated with a number of cognitive deficits, including difficulty concentrating, distractibility, forgetfulness,
reduced reaction time, memory loss, and indecisiveness [49]. The mechanisms behind the association between depression and cognitive
decline are not fully understood and different mechanisms have been proposed [43, 50, 51]. Depression could be a risk factor for
dementia, an early dementia symptom, a reaction to cognitive and functional disability, or a symptom of a related risk factor,
such as cerebrovascular disease [52].
Grey area: depression and memory
Treat depression because it’s a treatable illness, but relation to dementia
and dementia prevention not clear.
Grey area: depression and memory Classically described pseudo-dementia: “I don’t know”
- 50% of autopsy-confirmed AD (N=100) had a prior diagnosis of depression, peak incidence 2
y before AD dx
Jost and Grossberg in the Journal of the American Geriatric Society, 1996
Depressive symptoms in MCI do no explain memory scores
- Depression was independently associated with composite scores of executive functioning and specifically to
trails B
- Apathy was associated with poorer FAS
- Neither apathy nor depression associated with attention, memory, or language
- Apathy, but not depression, was associated with greater functional impairment.
- Depression and apathy are associated with different aspects of executive functioning in amnestic MCI, which
may reflect differing patterns of frontal lobe pathology.
Zahodne andTremont. International journal of geriatric psychiatry 28.1 (2013): 50-56.
My take home messages
Suspect if people have typical AD symptoms and mild functional changes
Important role of mood, anxiety, neuropsychiatric symptoms
o Much more complex than ‘pseudodementia’; treat depression and let’s see often not
enough
o Consider the personal and emotional reaction to diagnosis and prognosis: from denial to
catastrophe
o Suspect AD if there is the general anxiety/depressive prodrome of recent onset
Get as much collateral as possible
Do not blindly follow scanning, cognitive results
