Dementia Leslie Chang Evertson GNP Lead Dementia Care

Dementia Leslie Chang Evertson, GNP Lead Dementia Care Manager UCLA Alzheimer’s and Dementia Care Program 1

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 2

Overview Prevalence What is dementia? Diagnosis Causes Management 3

Prevalence of Dementia Age Range 65 -74 75 -84 85 and older % Affected 5% 15 -25% 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 4

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 5

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) 7

Not Dementia - Depression Sad and withdrawn/anxiety Concentration impaired Memory complaints prominent Orientation intact Sometimes called “Pseudodementia” Geriatric Depression Scale or PHQ-9 8

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 13

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 B 12 RPR & HIV if risk factors are present 14

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 that increase risk Age -CV Risk factors Family history -Head trauma APOE-E 4 -CKD Depression Factors that reduce risk (variable evidence) APOE-E 2 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 Aβ 42 Amyloid Imaging – Pi. B, 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 20

Diagnosing Dementia - Imaging Amyloid PET Scan Imaging 21

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 31

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 (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 B 6, B 12, 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 Reduced 30 mg for 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 49

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-withhiv-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/tg 2015/syphilis. htm UCLA Alzheimer’s and Dementia Care Program http: //dementia. uclahealth. org/ 52

Thank you Leslie Chang Evertson, GNP Lead Dementia Care Manager UCLA Alzheimer’s and Dementia Care Program 200 UCLA Medical Plaza Suite 365 A Los Angeles, CA 90095 Phone: (310)319 -3222 levertson@mednet. ucla. edu http: //dementia. uclahealth. org 53