Leslie Chang Evertson, GNP Lead Dementia Care Manager

UCLA Alzheimer’s and Dementia Care Program

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DISCLOSURES

None of the faculty, planners, speakers, providers nor CME committee has any relevant financial relationships

with commercial interest There is no commercial support for this CME activity

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Overview Prevalence What is dementia? Diagnosis Causes Management

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Prevalence of Dementia Age Range % Affected 65-74 5% 75-84 15-25% 85 and older 36-50%

US: ~5.4 million with Alzheimer’s (2013) > 13 million by 2050 World wide: ~35 million with Alzheimer’s(2013) >115 million by 2050

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Dementia Definition

DSM-IV Multiple cognitive deficits

Memory loss must be present One or more other deficit – aphasia (communication), apraxia

(motor execution), agnosia (recognition) , executive functions (synthesis)

Decline from prior level of function Deficits do not occur exclusively in the presence of

delirium DSM-V:

Memory loss not necessary Major Neurocognitive Disorder (NCD) vs. Minor NCD

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DSM-V Definitions

Major neurocognitive disorder (major NCD or dementia) Minor neurocognitive disorder (minor NCD) Either can be further characterized by cause

Alzheimer’s disease FTD LBD Parkinson’s disease

Not Dementia - Delirium

Acute confusion or delirium in the setting of a medical illness Often occurs in the hospital Frequently caused by medications Usually resolves (days to weeks) Many cases are probably preventable Confusion Assessment Method (CAM)

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Not Dementia - Depression Depression

Sad and withdrawn/anxiety Concentration impaired Memory complaints prominent Orientation intact Sometimes called “Pseudodementia” Geriatric Depression Scale or PHQ-9

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Not Dementia - MCI Mild cognitive impairment Cognitive complaint Objective impairment in 1+ domains Amnestic Non-amnestic

General function intact 6-15% per year progress to dementia

Amnestic MCI Prominent memory complaint Objective memory loss (1.5 SD below age

norms); other cognition intact May be single or multiple domains

Non-amnestic MCI Primarily affects other domains (executive, language,

visual spatial) May be single or multiple domains May be less likely to progress to dementia

Not Dementia – Normal aging

Patient more concerned than family Can describe details of forgetfulness Intact recent memory for important events Word finding difficulties Function preserved

Diagnosing Dementia Screening (raises suspicion) 3 item recall Mini-Cog (3 item recall plus clock drawing) GPCOG (GP Assessment of Cognition) MIS (Memory Impairment Screen) MMSE, MOCA, and others

Screening tests identify more than 90% with dementia but do not establish a diagnosis

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Diagnosing Dementia Clinician’s examination (usually PCP or Neurologist)

Mental Status Examination Physical Examination Psychosocial Examination Caregiver/Collateral input

Neuropsychological testing Lab and imaging tests to exclude medical conditions that

might be contributing Imaging: Structural MRI and/or Functional PET scan Labs: CBC, CMP, TSH, Vitamin B12

RPR & HIV if risk factors are present

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Neuroimaging

Most useful if: Age of onset< 60 year Focal neuro deficits Abrupt onset or rapid decline Predisposing conditions (e.g. cancer, anticoagulation)

AAN: either CT or MRI PET: approved to distinguish AD from FTD Amyloid PET scans: for research purposes only

Causes of Dementia Alzheimer’s Disease 60-80% Vascular dementia 10-20% Dementia with Lewy bodies 15% Frontotemporal dementia 5% Toxic-metabolic disorders 4% Other movement disorders 6%

Dementia Risk Factors Factors that increase risk

Age -CV Risk factors Family history -Head trauma APOE-E4 -CKD Depression

Factors that reduce risk (variable evidence) APOE-E2 Mediterranean-type diet (fruits, veggies, fish) Higher physical activity/exercise Mental activity

Alzheimer’s Disease-Clinical Memory Language Visual-spatial Higher level (executive) Apathy

Alzheimer’s Disease: 2011 3 stages

Preclinical: defined by changes in biomarkers MCI: biomarkers may help determine progression to

AD Alzheimer’s Disease: biomarkers may be helpful in

excluding AD as cause

Framework for Biomarkers Measures Related to Molecular Pathology of Abeta

CSF Aβ42

Amyloid Imaging – PiB, AV-45

Measures Related to Neuronal Injury CSF tau/phopho tau MRI measures structural change

Hippocampal Volume Medial Temporal Lobe Atrophy

PET or SPECT measures of functional change FDG PET – temporoparietal topographic pattern SPECT Perfusion – temporoparietal topographic pattern

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Diagnosing Dementia - Imaging

Amyloid PET Scan Imaging

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Natural History and Complications Progression of cognitive decline

3-4 points on MMSE/year Non-cognitive symptoms

Psychotic symptoms (20%) Depressive symptoms (40%) Agitation or aggression (80%)

AD survival after symptom onset 3-12 yrs; other dementias have worse survival

Clinical Characteristics of FTD Personality changes Executive dysfunction

Social disinhibition Behavioral impulsivity

Hyperorality Pick’s disease:

a rapidly-progressive form of FTD Pick’s bodies (balloon-like intracellular inclusions)

can be seen on autopsy

FTD versus AD Gradual but faster onset than AD Younger age of onset than AD

Age of onset < 60 years usually Memory and gait impairment later and not as

pronounced as with AD Relative preservation of visual-spatial skills

Clinical Characteristics of LBD Core features:

Visual hallucinations (VH) Parkinsonian signs Fluctuating alertness and attention

Suggestive features: REM sleep disorder Sensitivity to antipsychotic medications and extrapyramidal side

effects (EPS) Supportive features:

Frequent falls Syncope Autonomic dysfunction Delusions

LBD Versus Other Dementias LBD versus AD

Motor deficits are more prominent in LBD early in the course Memory deficits are more prominent in AD

LBD versus dementia associated with Parkinson’s disease (PD) Motor and memory deficits tend to arise together within a year in

LBD Motor deficits arise first in PD; memory impairment is a later

finding

Clinical Characteristics of Vascular Dementia

Abrupt onset (may not be present) Stepwise deterioration (may not be present) Cognitive symptoms and motor signs correlate with

ischemia on neuroimaging Prominent aphasia is common Patients tend to have CVA risk factors

Mild Dementia (MMSE 21-25) Functional impairments • Managing finances

• Driving • Managing medications

Cognitive changes • Decreased insight • Short term memory deficits • Poor judgment

Behavioral issues • Social withdrawal • Mood changes: apathy/depression

Complications • Poor financial decisions • AEs due to medication errors

Moderate Dementia (MMSE 11-20) Functional impairments • IADL

• Difficulty with some ADLs • Gait and balance

Cognitive changes • Disoriented to date and place • Worse memory • Getting lost in familiar areas • Repeating questions

Behavioral issues • Delusions/ Agitation/Aggression • Apathy/depression • Restlessness/anxiety/wandering

Complications • Inability to remain at home/ALF • Falls

Severe Dementia (MMSE 0-10) Functional impairments • ADLs including continence

• Mobility • Swallowing

Cognitive changes • Little or unintelligible verbal output • Loss of remote memory • Inability to recognize family/friends

Behavioral issues • Motor or verbal agitation/aggression • Apathy/depression • Sundowning

Complications • Pressure sores • Contractures • Aspiration/pneumonia

Alzheimer’s Disease: A Two-Phase Strategy

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Management Manage the disease

Cholinesterase inhibitors Memantine Vitamin E

Manage the patient Manage co-morbidities Caregiver support Behavioral therapies Drug management of complications Advanced planning

Manage the Disease Cholinesterase inhibitors

Donepezil (Aricept), galantamine (Razadyne) rivastigmine (Exelon)

May benefit Alzheimer’s Disease, LBD, Vascular (if also Alzheimer’s), and PD dementia

Do not benefit FTD Do not prevent progression of MCI to dementia

Effectiveness of Cholinesterase Inhibitors

Most often drug slows progression 10-25% of patients improve Behavioral symptoms may improve Some decline rapidly when drug discontinued

Memantine Memantine (Namenda) Slows rate of functional and cognitive decline and

improves behavioral symptoms FDA indication for moderate-severe AD Not effective in mild-moderate disease

Memantine plus Cholinesterase Inhibitor

Early studies showed better outcomes (cognition, activities of daily living, global outcome, and behavior) than cholinesterase inhibitor alone in moderate to severe dementia

But more recent studies have cast doubt on whether the combination is more effective

Vitamin E Mixed results in trials TEAM-AD VA Cooperative Trial

Mild-to-moderate dementia (MMSE 12-26) 4 arms (Vit E 2000 IU, memantine, both, none) Vit E slower rate of decline (19% per year) No benefit from memantine 42% did not complete the study

Jama 2014; 311:33-44.

Not Beneficial Vitamin B6, B12, or folate Gingko biloba Hormones (testosterone, estrogen) Statins Aspirin or other NSAIDs Vaccines Anti-amyloid treatment

Manage the Patient This is a lifelong disease Play the ball where it lies

If disease is early, include patient If late, rely on family and caregiver

Aim for the highest level of independence that works for everyone

Manage hot-button issues (e.g., driving) Manage other diseases Manage symptoms

Caregiver Support Caregivers are the most important resource a

demented patient has Over 50% develop depression The more knowledgeable and more empowered the

caregiver is, the better care the patient will receive Caregiver resources are available

Alzheimer’s Association and other community resources Counseling, Support Groups Respite – Hiring a help, Adult Day, placement

Management of behavioral and psychological complications

With medications:

Antidepressants Citalopram 30 mg for agitation

Reduced agitation Worsened MMSE scores Increased QTc

JAMA 2014;311:682-91

Management of behavioral and psychological complications

Antipsychotics (e.g., risperadone, quetiapine, olanzapine) Not very effective Have potential for side effects Some patients benefit

Mood stabilizing medications (e.g., valproate) Dextromethorphan/quinidine

JAMA 2015 Sep 22-29;314(12):1242-54

Behavioral Modifications

Reorient – Explain to the patient where he or she is and why he or she is there. Be sure to introduce yourself and speak in a confident yet reassuring tone. It is not always important to remind or correct the patient of the date, your specific title, etc.

Behavioral Modifications

Redirect – Divert attention by asking an unrelated question, ask the patient to help you with an activity or offer to take the patient for a walk.

Behavioral Modifications

Identify triggers – Did the patient become agitated during a bath? Medication? When he is in pain? Male or female caregivers? Daytime or nighttime? Family members?

Behavioral Modifications

Create a calm environment – This is difficult to do in a hospital setting. Perhaps the patient shares a room with another patient who has a lot of visitors or doctors; this can be anxiety producing. Avoid loud television, harsh lights, alarms, etc.

Behavioral Modifications

Offer a guess – Patients with dementia often cannot tell you what is bothering them. If they cannot find a word, offer some limited suggestions, don’t try to correct them. Try to avoid arguing with them.

Behavioral Modifications

Supervise – For some patients, memory impairment may be so severe, none of these interventions last but a minute or two. For these patients, sitters should be employed if possible before using sedation medications. http://www.alz.org http://dementia.uclahealth.org/body.cfm?id=68

And more to consider… Non-pharmacological behavioral modifications Caregiver stress and strain Financial resources Legal concerns Insurance coverage (Private insurance, Medicare, Medi-Cal, LTCi) Private caregiving Adult Day Care Support groups Assisted Livings Nursing Homes Unbefriended Elder abuse

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Conclusions Dementia is an epidemic, particularly among the oldest old Many diseases have symptoms of dementia but are not

dementia History taking and mental status exam are still critical

elements of diagnosis Diagnostic testing is generally confirmatory but occasionally

some surprises

Conclusions Providers can do much more for dementia patients now than a

decade ago Drugs to prevent disease progression and treat complications

are still limited Behavioral management and caregiver support are essential Potential new therapies are a long way off

Helpful Websites Alzheimer’s Association http://www.alz.org/ Lewy Body Dementia Association https://www.lbda.org/ The Association for Frontotemporal Degeneration

http://www.theaftd.org/ AIDS.gov https://www.aids.gov/hiv-aids-basics/staying-healthy-with-

hiv-aids/potential-related-health-problems/dementia/ National Institute of Neurological Disorders and Stroke

http://www.ninds.nih.gov/disorders/disorder_index.htm#V CDC – STD Treatment Guidelines

http://www.cdc.gov/std/tg2015/syphilis.htm UCLA Alzheimer’s and Dementia Care Program

http://dementia.uclahealth.org/

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Thank you Leslie Chang Evertson, GNP Lead Dementia Care Manager UCLA Alzheimer’s and Dementia Care Program 200 UCLA Medical Plaza Suite 365A Los Angeles, CA 90095 Phone: (310)319-3222 levertson@mednet.ucla.edu http://dementia.uclahealth.org

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