How to manage patients with subjective memory complaints or Mild Cognitive Impairment?

How to manage patients with subjective memory complaints or Mild Cognitive Impairment ?

Nicola T Lautenschlager, MD, FRANZCP

East of England Regional Old Age Psychiatrists Development GroupBedford Lodge Hotel, Newmarket

30th Sepember 2015

Professor of Psychiatry of Old Age, University of MelbourneDirector of Research, Aged Persons Mental Health Program, NWMH, MH

[email protected]

Park et al., Annu. Rev. Psychol., 2009;60: 173-96

Management of SMC and MCI

Diagnostic concepts to describe cognitive change in ageing


Benign senescent forgetfulness (BSF) – Kral, 1962 Mild Cognitive Impairment (MCI) – Reisberg et al., 1982 Age-Associated Memory Impairment (AAMI) – Cook et al., 1986 Late-life forgetfulness (LLF) – Blackford & La Rue, 1989 Age-Associated Cognitive Decline (AACD) – Levy et al., 1994 Cognitive Impairment No Dementia (CIND) – Graham et al., 1997 Amnestic Mild Cognitive Impairment (aMCI) – Petersen et al., 1999 Age Related Cognitive Decline (ARCD) – DSM IV Mild Cognitive Disorder (MCD) – ICD-10 Prodromal AD – Dubois et al., 2010 MCI due to AD – NIA-AA criteria; Albert et al., 2011 Mild Neurocognitive Disorder (MNCD) – DSM-5

Consensus panel using clinical judgement

Mild cognitive or functional impairment reported by the participant or informant not meeting criteria of dementia

or

Cognitive performance below expectation and at least 1.5 SD below norms

Consensus panel using clinical judgement

CIND present

Pattern of symptoms and neuropsychologicaltest results suggestive of prodromal AD

No other medical or neuropsychiatric conditions present to preclude and eventual diagnosis of AD

n=1770 approached; n=856 assessed

CIND Prodromal AD


Plassman et al., 2008


Plassman et al., 2008

8% died /a 12% demented /a


Memory complaint preferably qualified by an informant

Memory impairment for age and education

Preserved general cognitive function

Intact activities of daily living

Not demented

MCI

Winblad et al., 2004

Complaint from person or family member

Objective cognitive impairment

Change from normal functioning

Preserved overall general function, but some increased difficulty in activities of daily living

Not demented

Amnestic MCI

Petersen, 2007


Multidomain MCIMultidomain

MCI

No

Memory + otherMemory + othercognitive domainscognitive domains

No

Singlenon-memorydomain MCI

Yes

AmnesticMCI

Yes

SingleSinglenon-memorynon-memory

domaindomainimpaired?impaired?

No

Memory impairment only?Memory impairment only?Yes

Memory impaired?Memory impaired?

MCIMCI

Not normal for ageNot normal for ageNot dementedNot demented

Cognitive declineCognitive declineEssentially normal functional activitiesEssentially normal functional activities

Cognitive complaintCognitive complaint


Spangehl et al., Mayo Clinic; in press

Typical clinical/cognitive problems in MCI Changes in memory (more dependent on reminders, notes, diaries; misplacing things; etc.) More difficulties with multi tasking Changes is attention and executive functions (more easily distracted; less flexible; new difficulties with problem solving; less

skilled or interested in planning ahead (e.g. traveling)) Changes in language (word-finding difficulties) Changes in visuospatial function Often slower or more stressed (routines change) BPSD can occur Limited insight can occur (what is their theory?) Often increase in conflict with significant others (new safety concerns from family members; change of roles in family) IADLs can be impacted (new difficulties with driving in challenging situations; subtle new problems with managing finances;

cog. decline in skills; e.g. bridge, golf etc.)

Holsinger et al., 2007; Lautenschlager & Kurz, 2010; McCarten et al., 2013



Knopman & Petersen, 2014

Clinical assessment of cognition in old age

There is no ideal cognitive test for all situations

MMSE & clock drawing test are the most commonly used cognitive tests around the globe

Others are GPCOG, Mini-Cog, NuCOG, MOCA, CERAD, CAMCOG

Additional brief bedside tests can be added as needed (e.g. frontal lobe)

Rudas is useful for different cultural background

Geriatric Depression Scale (GDS-15) is a useful short depression scale

Ideal: thorough clinical assessment in combination with a detailed neuropsychological assessment (preferably by neuropsychologist)


1. Neurodegenerative brain disease (AD, PPD, LBD, FTD, etc.)

2. Cerbrovascular disease

3. Depression

4. Anxiety

5. Life events/ stressors/ personality

6. Organic factors

7. Post delirium

7. Various combinations of the above

Potential causes for MCI/CIND/SMC:


Villemagne et al., 2013

The long slow build up of pathology towards clinical AD

“The time between Aβdeposition and neurodegenerative or cognitive variablesalso requires caution: cognitive reserve, cardiovacular orcerebrovascular factors, and concurrent diseases might contribute to inter-individual variations in these intervals”


Lancet Neurology 2010;9:1118-27


Porteri & Frisoni, 2015

Biomarkers and MCI: an ethical challenge


Diagnostic label of „MCI“ usually given by specialist. Diagnsotic reasoning for this should be explained in detail to GP

Individual clinical presentation should determine how the diagnosis and prognosis should be discussed (clinical judgement)

Many specialists point out that research in this area is work in progress

Explaining in detail the individual test results (neuropsychology, imaging, etc.) can be helpful education for patient and family. It can validate concerns, put MCI in the medical context and alleviate anger, denial and guilt

Term „mild cognitive impairment“ sometimes might be seen as trivialising symptoms which cause great concern. Therefore explaining the context of „mild“ is crucial

Disclosure and impact of diagnosis


Disclosure of diagnosis Information on assessment results Individualised information on prognosis Pharmacological management options Reducing polypharmacy if possible Monitoring health and vascular risk factors Sleep, nutrition, falls Non-pharmacological approaches Information on research trials in the area Neuropsychiatric symptoms (35-75%: depression, apathy, anxiety, irritability) Discuss ADLs (including driving) Planning the future (e.g. finances, work, travelling, family duties, driving etc.) Information on AD treatment in case of progression “Carer” burden Information on useful contacts Regular follow-up appointments

Important points to consider with MCI in the clinical context



Cholinesterase inhibitor trials in MCI

Langa & Levine, 2015

No pharmacological approaches have yet shown significant improvements of symptoms or delay of progression in MCI (ChEI, memantine, ginkgo biloba, Piracetam, Rofecoxib, etc.)

Some discussion whether the donepezil & vitamine E RCT shows a reduced risk of progression in the first 12 months and even in the first 24 months for APOE e4 carriers

Cholinesterase inhibitors ± memantine are often prescribed for MCI (private)

Managing vascular risk factors is important

Pain, sleep, depression, anxiety

Pharmacological and medical management:


Management of SMC and MCI Langa & Levine, 2015

Langa & Levine, 2015

Approach for diagnosing & managing MCI

Risks factors for Alzheimers‘ Disease

Norton et al., 2014

Barnes & Lautenschlager, 2013

Potential underlying mechanisms


Barnes JN, 2015

Synergy of cognitive and cerebrovascular reserve?


Participants: 170, 50 years and older with Subjective Memory Complaints (SMC) with or without Mild Cognitive Impairment (MCI)Primary outcome: cognition (ADAS-cog) Aim: to perform for 24 weeks at least 150 min of moderate intensity physical activity in blocks of 3 sessions per weekTheory: stages of change and self efficacyResults: 1.3 points difference on the ADAS-cogSteps: 9000 moreAdherence: 78.2%

Pre-contemplationContemplation

PreparationMaintenance


-4

-3

-2

-1

0

1

2

3

4

Control Exercise

Mea

n C

hang

e in

Sel

f Effi

cacy

0-6 Months

0-12 Months

0-18 Months

Significant group x time interaction at 6 months:Self efficacy scores were 2.37 point higher (0.58, 4.16, < 0.01)

Cox K et al., 2013


To achieve the set minimum target of 150min PA per week.To improve physical health.To get fitter to be ready for future plans (e.g. travel/ excursions).To walk to the train instead of taking the car, etc.To walk to the shops back and forth.To be able to go for long beach walks with family.To improve self-esteem, e.g. to try more ambitious activities later on.To learn to be less stressed and more relaxed.To increase motivation for later activities (e.g. joining a walking group).To improve stamina to be able to keep up with others for future holiday activities.To improve cardiovascular health.To improve leg strength to reduce need to sit too much during the day.To get walking fit before buying a new dog.To get fit enough again to play social tennis.To increase fitness and confidence to ride the bike to work instead of using car.To reduce feelings of fatique, increase energy levels and mental attitude.To increase energy levels for more creative activities.To get fitter and more confident to use public transport to do more things.To get fit enough to play 18 holes of golf.To improve mood.

Participants: examples of individual goals

Lautenschlager et al., AAIC 2014


New PA in MCI/VCI results presented at AAIC 2015

US: 65 sedentary adults with MCI; 6-months moderate-to-high intensity aerobic exercise; 45-60min 4x per week; control group: stretching; sig. reduction in CSF tau levels, especially when > 70y; sig. increase in brain blood flow with improvement in attention, planning and organisational abilities (Baker et al., AAIC 2015)

Canada: 6-month aerobic exercise for n=71 participants with VCI; 3x 60min per week; control group: usual care + educational seminars on nutrition; sig. improvement of memory and selective attention; functional MRI showed improvement in brain efficiency (Liu-Ambrose et al., AAIC 2015)


Is a multidomain approach effective to prevent cognitive decline?

2 year multidomain trial with 1260 at risk community members (60-77y)Diet, PA, cognitive training, vascular risk monitoring or control group

Ngandu et al., 2015Management of SMC and MCI

Memory Assessment Clinical Questionnaire (MAC-Q)

As compared to when you were in your late teenage years or early 20s, how would you describe your abilities to perform the following tasks involving you memory ?

Crook et al., 1992

Severity of SMD and risk of progression – findings from AIBL study


Buckley et al., under review

Survival function for baseline SMD status (event: progression from SMD to MCI or AD) for 18, 36 and 54 months

N=58 high Ab burden ; n=230 low Ab burden (PET Ab)

SMD quartiles

Sig higher levels of depression and smaller left hippocampal volume in very high versus very low

No sig influence on episodic memory

12% progressed clinically to MCI or AD in Ab+ versus 4.3% in Ab-

High and very high sig more likely to change diagnosis compared to low and very low (HR = 5.1, 95% CI: 1.4-20.0, p = 0.02; adjusted for age and depression). No association in Ab-

Pietrzak et al., jamapsychiatry, 2015

The impact of anxiety in healthy Ab+ AIBL participants


N= 333 healthy participantsSMC or not


MCI and death

Contador et al., 2014

SMC and CIND is common in the older population and will rise The community is increasingly more educated about dementia risk Important for OAPs to have an approach to assess and manage SMC and MCI More research is needed to optimise assessment, management and risk

prediction Focusing on sub-groups might help to tackle the challenge of heterogeneity More service development is needed to be able to offer optimal management OAPs need to support colleagues in primary care to be aware of SMC and MCI Future drug trials will demand better identification of at risk patients Patients should be educated and encouraged to target modifiable risk factors Regular clinical follow-up is important

Conclusions


Any questions or comments?


How to manage patients with subjective memory complaints or Mild Cognitive Impairment?

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