Dementia Diagnosis and Prognosis EMILY MORGAN, MD 2020

OHSU INTERNAL MEDICINE AND GERIATRICS

Objectives

Define dementia and mild cognitive impairment

Identify and differentiate the 5 most common types of dementia

Explore key elements of treatment and prognosis in dementia

BILL

Creator:Raul RodriguezCopyright:© Fotoluminate LLC

Bill

82 year old man, recently moved to assisted living after his wife died 12 months ago.

His daughter has noticed increasing “forgetfulness” in the past 2-3 years. Bill has good days and bad days, but his family notices he has been neglecting his appearance recently.

No agitation or delusions, but occasional visual hallucinations. No loss of appetite or weight loss. He has had 2 falls in the last 3 months. Never smoked, rarely drinks.

Meds: HCTZ, baby aspirin, multivitamin and occasional diphenhydramine for insomnia.

Dementia defined by DSM-V:Major Neurocognitive DisorderDeficit in at least one objective assessment of:

◦ Complex attention

◦ Executive ability

◦ Learning and memory

◦ Language

◦ Visuo-constructional-perceptual ability

◦ Social cognition

Deficits must interfere with independence (ADLs/IADLs)

Mild cognitive impairment defined:Minor Neurocognitive Disorder

Minor cognitive decline from a previous level of performance in one or more of the stated domains

No interference with function but greater effort and compensatory strategies may be required to maintain independence

Why is MCI important?

50% progress to dementia within 7 years

There are interventions that can potential prevent or slow the rate of conversion to dementia

◦ Controlling vascular risk factors (OSA)

◦ Exercise (Tai chi)

◦ Diet (Mediterranean)

◦ Socialization (avoiding isolation)

Must rule out depression and delirium when assessing for

dementia!

6 types of dementia

Alzheimer’s

Vascular

Lewy Body

Frontotemporal

Alcohol related

HIV Associated

Dementia

45%

15%

20%

15%

5%

Alzheimers Vascular Mixed LBD FTD

Alzheimer’s Dementia

Impairment in learning and memory plus one:

◦ Complex attention

◦ Executive function

◦ Language

◦ Visuo-constructional-perceptual ability

◦ Social cognition

Vascular Dementia

New cognitive deficit +

Focal neurological signs and symptoms +/-

Brain imaging evidence of cerebrovascular disease

Judged to be temporally related to the dementia

MIXED vascular-Alzheimer’s dementia

Vascular insults are very common in Alzheimer’s disease

20% of patients have evidence of both vascular and Alzheimer’s pathology

Lewy Body Dementia

New cognitive deficits + 2/3 symptoms:

Parkinsonian findings:

shuffling gait, rigidity, dysphagia >>>tremor

Fluctuation in LOC and cognition

Well formed visual hallucinations

LBD – suggestive findings

REM sleep disorders

Severe antipsychotic sensitivity:Exaggerated extrapyramidal symptoms

Increased rigidity and bradykinesia

Frontotemporal Dementia

A TALE OF 2 DEMENTIAS

Frontotemporal Dementia: Behavioral variant

Decline in personal or social interpersonal conduct

Impaired reasoning and difficulty with tasks out of proportion to impairments in memory

Frontotemporal Dementia: progressive aphasia variant

Deficits in language out of proportion to memory impairment◦ Motor speech

◦ Word comprehension or object recognition

◦ Word retrieval or speech errors (substitution)

Alcohol related dementia

Deficiency in thiamine (Vitamin B1)

The toxic effects of alcohol on brain cells

The biological stress of repeated intoxication and withdrawal

Alcohol-related cerebrovascular disease

Head injuries from falls sustained when inebriated

Alcohol related dementia

Learning and memory most effected

Confabulation - making up information not remembered

People with alcohol related dementia many benefit from extended treatment with oral thiamine and magnesium

With treatment:

¼ will completely recover

½ will improve without complete recovery

¼ will remain unchanged

HIV Associated Dementia

Late stage disease: CD4<200 and high viral loads

Characterized by symptoms of cognitive, motor, and behavioral disturbances

Behavioral changes including apathy and social withdrawal

Motor changes include gait impairment, falls, impaired fine motor skills

No quick screening test validated – MoCA likely the best, also Modified HIV Dementia Scale

https://aidsetc.org/guide/hiv-associated-neurocognitive-disorders

The Mini Cog

◦ 3 item recall

◦ Clock draw

Quick memory Screen

Validated for diagnosis of dementia AND for MCI

Tests 5 brain domains

Tests 6 brain domains

Helps to assess driving ability

MoCA < 18Abnormal trails B

Abnormal clock

MMSE(proprietary- $1.68/use)

Tests 4 brain domains:

◦ orientation, memory, visual-spatial, verbal fluency

USE ONLY FOR FOLLOWING DEMENTIA OVER TIME

Physical ExamNeurologic Exam:

◦ Sensory, Reflexes, Strength, Motor Coordination

◦ E/o Parkinsonism?

◦ Gait assessment: Timed Get up and Go (TUG)

Lab studies

TSH

Vitamin B12 (MMA)Consider HIV and RPR

If none recently: CBC and metabolic panel

Neuroimaging

Non contrast CT scan or MRI

For any patients under age 65

Or patients over age 65 with:◦ Atypical presentation

◦ Unclear diagnosis

◦ Rapid unexplained deterioration

◦ Unexplained focal neurological symptoms

◦ History of head injury

◦ Urinary incontinence or gait ataxia early in illness

◦ Suspicion of undiagnosed CV disease

BILL

Creator:Raul RodriguezCopyright:© Fotoluminate LLC

BillSLUMS

Orientation 3/3

Calculation 1/3

Naming 2/3

Object Recall 3/5

Attention 1/2

Clock 0/4

Shapes 2/2

Story Recall 4/8

Total 16/30

BillGait – wide based, mild shuffling, TUG>15 sec

Tone – mild cog wheeling on L side

No tremor, normal facial movements

On further questioning, Bill has a long hx of “insomnia” caused by restless sleep. He has vivid dreams, often acting them out in his sleep.

Lewy Body Dementia

Now that my patient has a diagnosis, what next?

◦ Staging Dementia for treatment

◦ Behavioral symptoms assessment

◦ Driving assessment

◦ Home safety evaluation

◦ Caregiver burden

◦ Goals of care planning

Staging dementia

Mild

MoCA 20-16

Decline in IADLs, mild behavioral symptoms

Moderate

MoCA 15-10

Decline in ADLs, Increasing behavioral symptoms

Advanced

MoCA <10

Needing 24 hour care

End stage

FAST staging for hospice care

A review of Reviews – what works?

Laver K, Dyer S, Whitehead C, Clemson L, Crotty M. Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews. BMJ Open. 2016;6(4):e010767. Published 2016 Apr 27. doi:10.1136/bmjopen-2015-010767

ExercisePatient+Caregiver QOL interventionsAChE-IMemantine

Cholinesterase Inhibitors

Most studies with statistically significant difference favoring cholinesterase inhibitors

–Delay in progression of up to 7 months in mild dementia

–Delay of 2-5 months in moderate dementia

–Statistically significant improvement in behavioral symptoms in mild and moderate dementia

–Effective for all dementia types except FTD

Raina 2008, Rodda 2009

When to stop?

A Systematic Review of Practice Guidelines and Recommendations for Discontinuation of Cholinesterase Inhibitors in Dementia.

Renn BN, Asghar-Ali AA, Thielke S, et al.

Am J Geriatr Psychiatry. 2017;26(2):134-147.

Risk for Health Events After Deprescribing

Acetylcholinesterase Inhibitors in Nursing Home Residents

With Severe Dementia

Journal of the American Geriatrics Society, First published: 26 November 2019, DOI: (10.1111/jgs.16241)

Memantine

Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. Kishi et al. J Alz Disease, 2017.

Memantine showed a significant improvement

Cognitive 95% CI (-0.34, -0.15) p < 0.00001

Behavioral 95% CI (-0.34, -0.07) p = 0.003

Memantine

Studies in vascular, LBD, and FTD trend toward benefit

Dual therapy with AChE-I or monotherapy

Dose: 5mg daily -10 mg bid

eGFR of 30-60, max dose is 10 mg daily

Stop if eGFR below 30

Mild Dementia Alzheimer’s Vascular

mixedLewy Body FTD

Trial AChE-I Control vascular risk factors

Trial AChE-I

Trial AChE-I

PT/OT

Driving and safetyassessment

(NO AChE-I)

Trial memantine

Driving andSafetyassessment

Exercise (Tai chi) Mediterranean dietSocialization

Mild Dementia Conversations with patient and family:

What are your wishes?

What’s it going to look like?

Assisted living options

Advance Directive

Plan to stop driving

Moderate Dementia

AlzheimerSs Vascular mixed Lewy Body FTD

Trial AChE-I

Trial memantine

Control vascular risk factors

Trial AChE-ITrial memantine

Trial AChE-I

Trial memantine

Trial memantine

Moderate Dementia Conversations with patient and family:

What is our safety plan?

Neuropsychiatric symptoms

Yes and… approach to communication

Memory care options

POLST

Advanced Dementia Alzheimer’s Vascular

mixedLewy Body FTD

Considerstopping AChE-I

Trial memantine

Consider stopping AChE-I

Trial memantine

Considerstopping AChE-I

Trial memantine

Trial memantine

Advanced Dementia Conversations with caregiver:

24 hour caregiving

Planning for end stages◦ Loss of mobility◦ Loss of verbal interaction◦ Complete Incontinence◦ Dysphagia◦ Weight loss

References Laver K, Dyer S, Whitehead C, Clemson L, Crotty M. Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews. BMJ Open. 2016;6(4):e010767. Published 2016 Apr 27. doi:10.1136/bmjopen-2015-010767

Lockhart IA, Orme ME, Mitchell SA. The efficacy of licensed-indication use of donepezil and memantinemonotherapies for treating behavioural and psychological symptoms of dementia in patients with Alzheimer’s disease: systematic review and meta-analysis. Dement Geriatr Cogn Dis Extra. 2011;1(1):212–27.

McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;2:CD003154.

Raina, P, et al. Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline. Ann intern Med. 2008;148: 379-397.

Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr. 2009;21(5):813–24.

Stinton, et al. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2015 Aug 1; 172(8): 731–742. Published online 2015 Jun 18. doi: 10.1176/appi.ajp.2015.14121582.

Wang H, Yu J, Tang S, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry 2015;86:135-143.

Questions???