Personal Reflections on the Design and Delivery of Services to Those with Cognitive Disorders

Dr. David B. Hogan Brenda Strafford Foundation Chair in Geriatric Medicine

University of Calgary

Conflicts of Interest

• None to declare

Objectives

• Review evidence-based approaches to the design and delivery of services for those with cognitive disorders

• Reflect on the current structure of services in our own jurisdiction

• Identify key barriers to restructuring services and approaches to dealing with them

Few Things First

Effects of Medical Research on Treatment Cost & Disease Duration

Polio

Dementia Doesn’t = Alzheimer

• Multiple potential causes of dementia that are present alone or in combination

• Commonest (older adults)– Alzheimer’s disease– Combination (e.g., AD with cerebrovascular or Lewy body

disease)• Common (older adults) – Dementia with Lewy Bodies, Vascular Dementia (Mixed

Dementia), Frontotemporal Dementia• Rarer causes – Alcohol-Related, Associated with Parkinson’s Disease,

Huntington’s Chorea, Prion Disease (CJD), AIDS-Related, Neurosyphilis, etc…

Autopsy Studies - Mixed Disease Common in Old Patients

• Camberwell Dementia Case Register (avg. age 82)– Mixed pathology in 34% - Br J Psychiatry 1999, 174:45-50

• State of Florida Brain Bank (average age of death 79)– 40% had more than 1 relevant CNS post-mortem

diagnosis - Alz Dis Related Disord 2002, 16:203-12 • Rush Memory and Aging Project (avg. age 88)– 70% without dementia had brain pathology (e.g., AD,

infarcts, Lewy bodies) – All with dementia had pathological changes with over 50%

having multiple diseases, which increased by 3-fold risk of dementia - Neurology 2007, 69:2197-04

Alzheimer Disease

• Most common cause (alone or in combination) in older adults – 60% of all cases

• NINCDS-ADRDA (1984) – Clinical-pathological entity - dementia and AD changes

in brain coupled

Diseases

• “Despite the efforts of purists, academics and dictionaries, definitions must evolve along with knowledge and concepts. The logic of words must always yield to the logic of facts they symbolize” - René Dubos (White Plague)

Changes in How AD Viewed

• AD pathological changes and cognitive deficits develop over many years– Dementia is the end stage (dementia and AD

decoupled) – Initial event felt to be disordered beta amyloid

metabolism (but still hypothesis)

Genetics

• Causative mutations (< 5%; suggested by early onset, autosomal dominant pattern) • APP (chromosome 21)• Presenilin 1 or PS1 (chromosome 14)• Presenilin 2 or PS2 (chromosome 1)

• Latter two both part of gamma secretase complex• Down Syndrome (trisomy 21) • Three copies of the gene for APP

• Risk factor for late onset (65+) AD• Apolipoprotein E4 allele (chromosome 19) - dose

dependent relationship (homozygous > heterozygous) for risk at certain ages & earlier age of onset but not necessary or sufficient

Biomarkers

• Biomarkers – major ones– Beta amyloid pathology

• Amyloid PET imaging and low levels of beta amyloid 1-42 in CSF

– Neuronal injury • High levels of tau and phospho-tau in CSF

– Neuronal dysfunction • Decreased metabolism in parietal-temporal lobes on FDG

PET– Neurodegeneration

• Temporal, parietal, and/or hippocampal atrophy on MRI

NIA-AA Criteria for Diagnosis of AD

• Three separate work groups appointed by NIA and AA (“balanced expertise & international representation from academia and industry”)

• Met during early-mid 2010 & came up with recommendations

• Presented at the 2010 International Conference on Alzheimer’s disease then posted on AA webpage for public comments

• Revisions and harmonization in fall of 2010• Final version in early 2011 (published that year by

Alzheimer’s & Dementia)

15

New Criteria - Dementia Due to AD• No major change in how dementia defined• Probable AD dementia– Dementia + insidious onset, clear history of worsening,

amnestic (most common) or nonamnestic (language, visuospatial, executive) presentation

– No substantial cerebrovascular disease, dementia with Lewy body, frontotemporal degeneration, or other neurological or non-neurological condition (co-morbidity or medication) that could have substantial effects on cognition

– More certain if documented decline or carry causative gene (carriage of E4 not sufficiently specific)

16

Dementia Due to AD

• Possible AD dementia– Either atypical course (e.g., abrupt onset or

insufficient data on decline) or have mixed causation• Probable or Possible AD dementia with evidence of

the AD pathophysiological process– Biomarkers of amyloid deposition or downstream

neuronal degeneration … but not recommended for routine use

17

MCI Due to AD• Core clinical criteria– Concern about a change in cognition (patient,

informant, or clinician), impairment in 1+ domains (typically includes memory), independence in functional abilities, and not demented

– To determine if etiology consistent with AD – R/O other causes, look for longitudinal decline, and see if carry genetic risk factor (a causative mutation or E4)

18

Preclinical Stage

• Solely intended for research purposes and “do not have any clinical implications at this time”

• Three stages– Asymptomatic cerebral amyloidosis (beta amyloid in CSF,

PET amyloid imaging)– Amyloid positivity + evidence of neuronal injury (tau, FDG-

PET, MRI)– Amyloid + neuronal injury + subtle cognitive changes

Note: International Working Group suggested the term Pre-symptomatic AD for those carrying causative mutation - Lancet Neurology 2010, 9:1118-27

19

Fig. 3

Source: Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011; 7:280-292 (DOI:10.1016/j.jalz.2011.03.003 )

Copyright © 2011 Terms and Conditions

Hypothetical Model

20

Advantages

• Dementia and AD decoupled– By time dementia present, pathological changes have been

occurring for 25 years (N Engl J Med 2012, 367:795-804) with many neurons lost; the hope is earlier diagnosis might enable effective treatment before they are lost

• Might lead to more accurate diagnosis • Might help with research– ? Biomarkers surrogate outcome in prevention studies– ? Enrollment of those with more certain diagnosis

21

Alzheimer Disease Pathology without a Dementia

• Older individuals at autopsy can have high density of AD lesions but no dementia – ? Plaques and tangles are epiphenomena (a secondary

phenomenon occurring alongside/ in parallel to primary process)

– ? Slow accumulation of plaques and tangles easier to deal with than rapid (i.e., cell repair mechanisms, compensation, presence of factors slowing down cascade of events)

– ? Predisposing - need precipitant/ 2nd disease– ? Cerebral/ cognitive reserve

22

Concerns - Pre-Clinical Stage• Suggested as research criteria but fear will start (&

has started) to be used more widely – MRIs, amyloid/ FDG-PET scanning & spinal taps available

now• Uncertainty re cut-points and need standardization• Uncertainty re actual risk of dementia (+ for MCI)

– Cost • Of the investigations (+ if used for MCI and dementia work-up) • Cost (and harm) of further tests and therapies• Opportunity costs

– Labeling if have a + biomarker• CSF AD pattern found in more than 1/3 of cognitively normal 75

year olds – Arch Neurol 2010, 67:949-56– For what purpose? No disease modifying therapy available

DSM-5

• Change because– Believed “dementia” stigmatizing and not well

accepted – Should focus on decline from a previous level of

functioning as opposed to a deficit– Memory impairment not first domain affected in all

neurocognitive disorders– To align better with neurological practice

Approach Suggested in DSM-5

• First establish the presence of a neurocognitive disorder base on assessing cognitive domains – Complex attention, executive function, learning & memory,

language, perceptual motor, social cognition

• Then classify as Delirium, Mild Neurocognitive Disorder (mild cognitive impairment) and Major Neurocognitive Disorder (formerly dementia)

• Then specify whether– Alzheimer, frontotemporal, Lewy body, vascular, traumatic

brain injury, substance/ medication, HIV, prion, Parkinson, Huntington, another medical, multiple, unspecified

Major Neurocognitive Disorder

• Evidence of significant cognitive decline in 1+ cognitive domain based on– Concern of person, knowledgeable informant, or

clinician that there has been significant decline– Substantial impairment in cognitive performance

• Cognitive deficits interfere with independence in everyday activities

• Do not occur exclusively in the context of delirium• Not better explained by another mental disorder

(e.g. major depression)

Minor Neurocognitive Disorder

• Similar except– First point: “… modest decline … mild decline …

modest impairment”– Second point: don’t interfere with capacity for

independence in everyday activities – complex ones are preserved but greater effort, compensatory strategies, or accommodation may be required

Push to Screen for Pre-dementia

• Feed into belief there is value in identifying milder forms of cognitive impairment– Stems from conviction that dementia is an illness that

progresses through a mildly symptomatic stage where interventions are more effective

– Concerns that much that can be done is “simply good practice”, unproven benefits of many interventions, nothing conclusively shown to prevent progression, costs, and diversion of resources – BMJ 2013, 347:f25 doi:10:113651

27

28

Lancet Neurology 2010, 9:702-16

29

Why Do So Many Alzheimer’s Drugs Fail in Clinical Trials? (Time, August 26/10)

• Of 13 Phase 3 drugs in previous slide, 12 have failed to date (Fall 2013)

• Some recent high profile amyloid-based failures – Semagacestat - gamma secretase– R-flurbiprofen - gamma secretase– Tramiprosate - prevent aggregation– Solanezumab/ bapineuzumab – monoclonal antibodies to

beta amyloid

What Works?

30

Cochrane Database

• Pharmacotherapy– AD - ChEIs are efficacious for mild-moderate AD;

despite variations in modes of action, no evidence of any differences between them with respect to efficacy; one large trial shows fewer AEs with donepezil Vs. rivastigmine - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 5, 2012

– PDD/DLB - available evidence supports the use of cholinesterase inhibitors in patients with PDD; he effect in DLB remains unclear - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 3, 2012

31

Cochrane Database

• Pharmacotherapy– VCI: some evidence of benefit with ChEIs/ more

studies needed - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews.4 & 5, 2013

– MCI: little evidence that ChEIs affect progression to dementia or cognitive test scores that is overwhelmed by the increased risk of adverse events, particularly GI; ChEIs not recommended for mild cognitive impairment - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 9, 2012

32

Cochrane Database

• Pharmacological– Atypical antipsychotics – risperidone & olanzapine

reduce aggression + risperidone reduces psychosis but both associated with serious AEs; neither should be used routinely unless severe distress or risk of harm to others - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 5, 2012

– Halperidol – reduces aggression but associated with AEs; no evidence to support routine use for other manifestations of agitation in dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 5, 2012

33

Cochrane Database

• Valproate preparations are ineffective in treating agitation among demented patients & are associated with an unacceptable rate of AEs - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 12, 2010

• Antidepressants for agitation/ psychosis - the SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies; both SSRIs appear to be tolerated reasonably well when compared to placebo, typical antipsychotics and atypical antipsychotics - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 2, 2011

34

Cochrane Database

• Insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

• No evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

35

Cochrane Database

• Pharmacotherapy– Many with AD dementia & NPS can be withdrawn

from chronic antipsychotic Rx without detrimental effects on behaviours but in 2 studies where agitation/ psychosis responded well pts. were more likely to relapse after stopping + 2 studies suggest those with more severe symptoms could benefit from continued therapy; programs to could be incorporated into routine practice with above qualifications - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2013

36

Cochrane Database

• Non-pharmacological– Consistent evidence that cognitive stimulation

programs benefit cognition in mild-moderate dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 2, 2012

– Functional analysis (FA) for challenging behaviours (i.e., explore meaning or purpose of a person's behaviour) - potential beneficial effects of multi-component interventions that utilize FA but too early to draw conclusions about efficacy - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 2, 2012

37

Cochrane Database

• Non-pharmacological– Multi-component, tailor-made psychosocial

interventions can reduce carers' psychological morbidity and delay their relatives' institutionalization - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 11, 2011

– There is evidence supporting the effectiveness of psychosocial interventions for reducing antipsychotic medication in care home residents - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 12, 2012

38

Cochrane Database

• Non-pharmacological– Reminiscence Therapy - number of promising results

in studies but in view of limited number & quality of studies, the variation in types of reminiscence work reported and the variation in results between studies, more studies needed - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 1, 2009

– Insufficient evidence from RCTs allow any conclusion about the efficacy of validation therapy for people with dementia or cognitive impairment

39

Cochrane Database

• Music Therapy - methodological quality too poor to draw useful conclusions - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 3, 2011

• Aroma therapy – RCTs needed before conclusions can be made - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

• No convincing evidence supporting efficacy of snoezelen (multi-sensory stimulation) for dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

• Insufficient evidence to assess value of light therapy for dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

40

Cochrane Database

• Non-pharmacological– Available evidence regarding cognitive training for

mild/ moderate dementia remains limited & of poor quality; no indication of any significant benefit - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 6, 2013

– Available literature fails to demonstrate the benefit of driver assessment for either preserving transport mobility or reducing motor vehicle accidents - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 8, 2013

41

Cochrane Database

• Insufficient evidence to be able to say whether or not physical activity programs are beneficial for people with dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

• Current evidence does not demonstrate benefits or AEs from the use of respite care for people with dementia or their caregivers; these results should be treated with caution as they may reflect the lack of high quality research in this area rather than an actual lack of benefit - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

42

Cochrane Database

• Insufficient evidence to suggest that enteral tube feeding is beneficial in patients with advanced dementia - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2009

• Special Care Units (SCUs) – no RCTs on the effects of SCUs on behavioural symptoms in dementia & no strong evidence of benefit from available non-RCTs; probably more important to implement best practices than to provide a specialized care environment - Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 5, 2012

43

44

Cost-effectiveness of Prevention, Care and Treatment Strategies for Dementia

• Pharmacological interventions– Cholinesterase inhibitors, memantine

• Non-pharmacological– Cognitive stimulation, exercise, occupational therapy,

caregiver interventions, care management

• Barriers– Limited research base, difficulty generalizing from available

studies, narrow perspective when measuring cost, reluctance to act on data, fragmented care

Int J Geriatr Psychiatry 2012

Common Elements

• Diagnosis – primary & secondary• Advance care planning• Support to patient & family• Develop & implement treatment plan – Referrals as needed

• Continuity of care – Monitoring over time– Case (or care) management

• Mobilize “dementia friendly” community- and facility-based services as needed – CMAJ 2008 179:1019-1026

45

2009 Action Plan - Meeting the Challenge of Alzheimer’s Disease and Related Disorders

• Increase knowledge & adopting different attitudes • Provide access to co-ordinated, personalized services

• Enhance quality of life and care – In alternative living facilities – At the end of life – For family/informal caregivers

• Professional & support staff training • Research 46

Barriers

• To implement recommendations need to: – Ensure clinicians are adequately trained & motivated– Required resources and services are available– Explore different models of care

47

Training

• Many health care providers are uninformed• Educational needs among primary care physicians– Knowledge about local diagnostic & support services– Assessment & communication skills– Management of behavioral problems– Coordination of support services

• Skeptical about the effectiveness of available interventions

48

Guideline Adherence

• Poor by physicians without interventions• Common obstacles identified by Canadian physicians

– Inadequate time– Inadequate remuneration– Lack of accessible community resources

49

Potential Solutions

• Every community should examine the services locally available, assess their adequacy, and implement plans to deal with identified deficiencies– Coordination and competition

• Models of care– Modified (i.e., less reliance on promotion of patient self-

management coupled with greater caregiver involvement) chronic disease management

– Shared care models should be developed and evaluated

• Dementia care must be adequately funded (globally) and reimbursed (at the level of the practitioner)

50

51

Up-front Costs Could be Revenue Neutral if Effective Over Time

• UK – nationwide memory services for early diagnosis and intervention for dementia– Modeling indicates that if the service can achieve

modest increase in average quality of life of people with dementia and “divert” 10% from residential to community care it would be cost-effective – but would take 4-10 years to see

Int J Geriatr Psychiatry 2009

Merci/ Thank You

52