Cognitive Impairment – What Not to Forget - PowerPoint Presentation

Cognitive Impairment – What Not to Forget Bruce Margolis, DO, MBAApril 25, 2017 17-73

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What We’re Going to Talk About What is cognitive impairmentThe spectrum of cognitive disordersEpidemiology of cognitive disordersMild Cognitive Impairment Risk factors for Alzheimer’s disease The mortality of cognitive impairment The morbidity of cognitive impairment Screening for cognitive impairment Cognitive screening and mortalityNeuropsychological testingUnderwriting approach 3 of 42

What is Cognitive Impairment DSM-5* CriteriaDecline in one or more cognitive domain based on Concern about decline, expressed by individual or reliable informant, or observed by clinicianDocumented by objective cognitive assessment That is Not exclusively during delirium Not better explained by another mental disorder 4 of 42 Source adapted from: *American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition, Arlington, VA, American Psychiatric Association; 2013

What is Cognitive Impairment Mild Cognitive Impairment (MCI) Due to Alzheimer’s Disease (AD)Establish clinical and cognitive criteriaCognitive concern reflecting a change in cognition reported by patient, informant or clinician Objective evidence of impairment in one or more domains, typically including memory (amnestic) Examine etiology of MCI consistent with AD pathophysiological process Rule out vascular, traumatic, medical causes of cognitive decline, where possible Provide evidence of longitudinal decline in cognition when feasible Report history consistent with AD genetic factors, where relevant 5 of 42 Source: Albert MS, et al. Alzheimer’s & Dementia 2011;7:270

What is Cognitive Impairment DementiaCognitive or behavioral symptoms that: Interfere with ability to function at work or at usual activitiesRepresent a decline from previous levels of functioning Are not explained by delirium or psychiatric disorder Cognitive impairment detected by history and cognitive testing The cognitive or behavioral impairment involves a minimum of two of the following domains: Impaired ability to acquire and remember new information Impaired reasoning and handling of complex tasks; poor judgment Impaired visuospatial abilities Impaired language functions (speaking, reading, writing) Changes in personality or behavior 6 of 42 Source: McKhann GM, et al. Alzheimer’s & Dementia 2011;7:263

What is Cognitive Impairment 7 of 42 Source: Alzheimer's & Dementia: The Journal of the Alzheimer's Association . DOI:10.1016/j.jalz.2011.03.003

The Spectrum of Cognitive Disorders Alzheimer’s disease – 60-80% casesVascular/Multi-infarct dementia - ~10% cases – due to cerebrovascular disease – infarctsMixed – may be more common than appreciated Dementia with Lewy bodies (DLB) – visual hallucinations, Parkinson-like features Frontotemporal dementia (FTD) – personality and language changes Parkinson’s disease Creutzfeldt-Jakob disease – prior induced, rapidly advances Huntington’s disease – inherited neurodegenerative disorderDown’s syndrome – almost all develop AD 8 of 42 Source: http :// www.alz.org/dementia/types-of-dementia.asp. Accessed 2/9/17

Epidemiology of Cognitive Disorders Prevalence of MCI estimated to be from 16-20% in adults 60 and older20-40% of those with MCI will evolve to dementia over time at a rate of 10-15%/yearNot all individuals with MCI will go on to develop dementia Up to 20% will improve over time 9 of 42 Source: Kelley RE. MCI/Alzheimer’s Disease. 2017 ACLI Medical Section Annual Meeting

Epidemiology of Cognitive Disorders 10 of 42 Source: 2016 Alzheimer’s Disease Facts and Figures, Alzheimer’s Association. http://www.alz.org/ri/documents/facts2016_report(3).pdf

Epidemiology of Alzheimer’s Disease 11 of 42 Source: 2016 Alzheimer’s Disease Facts and Figures. Alzheimer’s Association 2016

Alzheimer’s Disease Risk Factors Confirmed risk factorsAgeGeneticsChromosomal disorder – Down Syndrome individuals at high risk to develop AD Rare familial disorders – single gene mutations (APP*, PSEN**1, PSEN2) – autosomal dominant pattern Complex – most AD cases combination of genetic susceptibility (APOE***4) and environmental risk factors Likely risk factors Head trauma – traumatic brain injury (TBI) Cardiovascular risk factors - hypertension, obesity, diabetes, high cholesterol, inflammatory markers Cardiovascular disease – stroke, heart disease Depression 12 of 42 *APP = amyloid precursor protein; **PSEN = presenillin; ***APOE = apolipoprotein E Source: 2016 Alzheimer’s Disease Facts and Figures. Alzheimer’s Association 2016

Mortality of Cognitive Impairment Cognitive Impairment and Mortality in the Cardiovascular Heart StudyMulti-center study of Medicare eligible individuals5888 persons from 1989-1999 Predominantly C aucasian Cognitive impairment based on Mini Mental Sate Exam (MMSE) scores Analyzed six groups(1) All persons with/without cognitive impairment(2) All persons based on severity of cognitive impairment (3) All persons with co-morbids with/without cognitive impairment (4) All persons with co-morbids based on the severity of cognitive impairment (5) All persons otherwise healthy with/without cognitive impairment (6) All persons otherwise healthy based on severity of cognitive impairment 13 of 42 Source: Shavelle RM, et al. J Ins Med 2009;41:110

Mortality of Cognitive Impairment Group 2 (RR)* Group 4 (RR) Group 6 (RR) Mild Cognitive Impairment 1.31 1.19 2.01 Moderate Cognitive Impairment 1.59 1.5 5.25 Severe Cognitive Impairment 2.4 1.98 No data 14 of 42 Source: Shavelle RM, et al. J Ins Med 2009;41:110 *RR = Relative Risk of Death Shavelle Study Results

Mortality of Dementia Survival After Initial Diagnosis of Alzheimer’s DiseaseBase population 23,000; age 60+; Seattle based health maintenance organization (HMO)521 newly diagnosed persons with Alzheimer’s; 1987-1996 Population predominantly C aucasian Followed on average 5.2 years Median survival for men 4.2 yearsMedian survival for women 5.7 years 15 of 42 Source: Larson EB, et al. Ann Intern Med 2004;140:501

Mortality of Dementia 16 of 42 Source: Larson EB, et al. Ann Intern Med 2004;140:501

Morbidity of Cognitive Impairment 17 of 42 Source: Society of Actuaries LTC Experience Committee Sixth Intercompany Report – June 2011 Long Term Care (LTC) Insurance Industry Claims Experience

Screening for Cognitive Impairment 1st Generation Screening TestsMini-Mental State Exam (MMSE) Short Portable Mental Status Questionnaire (SPMSQ) Clock Drawing 2 nd Generation Screening TestsDelayed Word Recall (DWR)Minnesota Cognitive Acuity Screen (MCAS)* 3 rd Generation Screening Tests Enhanced Mental Skills Test (EMST)** 18 of 42 *Test proprietary to LTCG® **Test proprietary to LifePlans, Inc.

Screening for Cognitive Impairment Cognitive Screening Test Sensitivity (Sn) Specificity (Sp) MMSE 59-92% 62-92% SPMSQ 55-92% 71-87% DWR 89-96% 98-100% MCAS (dementia) 97.5% 98.45% EMST¹ (normal vs. MCI/MD)* (normal vs. MD) 96% 96% 91% 99% 19 of 42 *MCI = mild cognitive impairment; MD = mild dementia Source: Yoes ME, et al. Development and Standardization of a New Cognitive Screening Test: The Minnesota Cognitive Acuity Screen (MCAS), March 1999 ¹Shankle WR, et al. PNAS 2005;102:4919

Screening for Cognitive Impairment 20 of 42 Source: Sachdev , P. S. et al. (2014) Classifying neurocognitive disorders: the DSM‑5 approach Nat. Rev. Neurol. doi:10.1038/nrneurol.2014.181 Neurocognitive Domains

Screening for Cognitive Impairment Cognitive Domain Method of Assessment Orientation Person, place, time Registration Repeat 3 objects Memory Recall 3 words at 3 minutes Attention 3-stage command Calculation Serial 7 subtraction Language Naming, repetition, reading, writing Visuospatial Ability Geometric figure 21 of 42 Mini-Mental State Exam (MMSE) Maximum score 30. Score 24/30 or less suggests possible dementia. (Source: http :// www.alz.org/alzheimers_disease_steps_to_diagnosis.asp#mental) Pay close attention to delayed recall.

Screening for Cognitive Impairment Clock Drawing Test (CDT)Method – draw face of a clock, mark in the hour numbers, draw hands to indicate a specified time (e.g., 11 past 10)Assesses attention, language, memory, visuospatial ability and executive functions Several different scoring methods Shulman scale 0-5 points Reproducible Sn/Sp – 86%/72% Fair correlation with MMSE 22 of 42 Source: Mainland BJ, et al. Int J Geriatr Psychiatry 2014;29:127

Screening for Cognitive Impairment 23 of 42 Source: http :// www.dementiaguide.com/images/DGI-Ill_5.1-ClockDrawing.jpg. Accessed 2/6/17

Screening for Cognitive Impairment Delayed Word Recall (DWR)Encoding PhaseExaminer speaks/shows 10 words (nouns), one at a timeIndividual repeats each word and uses the word in a sentence Delay Interval 5 minute delay Recall Phase Individual recalls as many words as possible 24 of 42 Source: Weir D. Cognitive Test Selection for the Harmonized Cognitive Assessment Protocol (HCAP) October 2014

Screening for Cognitive Impairment Delayed Word RecallEarly stage Alzheimer’s patients have rapid rate of forgetting within first 5-10 minutesElaborative encoding provides benefit to normal subjects but not to those with Alzheimer’sOverall predictive accuracy 95% in identifying Alzheimer’s patients from normal controls (Knopman & Ryberg. Arch Neur 1989;46:141) May be difficult to differentiate depression from Alzheimer’s disease (O’Carroll, at al. Psych Med 1997;27:967)Can be administered via phone or in person, though risk of cheating significant when done via phone 25 of 42

Screening for Cognitive Impairment Minnesota Cognitive Acuity Screen (MCAS)Developed for telephonic useTests 9 domainsPublished research Impaired group – 210 elderly nursing home residents with dementia (avg. age 82.4 yrs) Unimpaired group – 129 community dwelling seniors without dementia (avg. age 73.8 yrs) Weighted analysis of each domain score u sed to discriminate impaired from unimpairedReported Sn 97.5%; Sp 98.5% 26 of 42 Source: Knopman , DS, et al. Neuropsychiatry, Neuropsychology, and Behav Neuro 2000;13-286

Screening for Cognitive Impairment Domain Assessment Orientation Person, place, time Attention Multiple digit repetition Memory Delayed word recall (10 words) Language Follow multi-step command Repetition Sentence repetition Naming Identify object described Computation 8 simple math problems Judgment 4 judgment questions Verbal Fluency Name fruits and vegetables 27 of 42 Minnesota Cognitive Acuity Screen Source: Knopman , DS, et al. Neuropsychiatry, Neuropsychology, and Behav Neuro 2000;13-286

Screening for Cognitive Impairment Minnesota Cognitive Acuity ScreenHigh Sensitivity/SpecificityIncremental improvement over MMSE and DWR Can be used telephonic or face-to-face Convenience sample used in study – could impact discriminating ability of test Not validated against mild dementia or mild cognitive impairment Potential for cheating exists as with any telephonic tool 28 of 42 Source: Knopman , DS, et al. Neuropsychiatry, Neuropsychology, and Behav Neuro 2000;13-286

Screening for Cognitive Impairment Enhanced Mental Skills Test (EMST)Developed by Medical Care CorporationBased on Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word battery and validated in study published in 2005High sensitivity for detecting MCI Multiple domains 9 balanced word lists No reliance on a single cut-off score Can be administered via phone or face-to-face 29 of 42 Source: Shankle WR, et al. PNAS 2005;102:4919 Source: LifePlans , Inc.

Screening for Cognitive Impairment EMST Test ComponentsComprehensionApplicant must respond to simple, clear directionsThree Learning Trails of 10 Words Each Repetition and Encoding: applicant repeats each word to assure correct encoding Working Memory: applicant immediately recalls as many words as possible Metamemory/Judgment and Insight Applicant is asked to estimate the number of words she/he will recall in the delayed word recall Abstract Reasoning: Distraction Phase: Triadic Animal Comparison Applicant chooses which of three animals is least similar 9 animals, 12 sets of comparisons Roughly 3-5 minutes to complete Task is largely independent of race, culture and individual differences 30 of 42 Source: Shankle WR, et al. PNAS 2005;102:4919 Source: LifePlans , Inc.

Screening for Cognitive Impairment EMST Test ComponentsImmediate and Delayed Word RecallApplicant recalls as many of the original 10 words as possible Delayed Cued Recognition: Item Cues Applicant is asked if specific words were included in original word list Delayed Cued Recall: Category Cues Applicant recalls as many animals from triadic comparison as possible 31 of 42 Source: Shankle WR, et al. PNAS 2005;102:4919 Source: LifePlans , Inc.

But……….. 32 of 42 d oes cognitive screening work????

Cognitive Screening and Mortality 33 of 42 Source: Vecchione L, Golus E. J Ins Med 2007;39:264

Cognitive Screening and Mortality 34 of 42 Minnesota Cognitive Acuity Screen (MCAS) and Mortality Source: Hauser, P. On the Risk 2010; 26:54

Cognitive Screening and Mortality EMST and MortalityThe Relationship Between Cognitive Impairment and Mortality Among Long Term Care Insurance Applicants (LifePlans Study)Analyzed mortality data based on DWR and EMST results Telephonic and in-person assessments from 1996 through 2008 Mortality data from Social Security Death Master File DWR 764,037 lives 5.8 million exposure years160,255 deathsEMST 132,719 lives 376,000 exposure years 2,263 deaths 35 of 42 Source: Cohen MA, et al. Society of Actuaries 2011

Cognitive Screening and Mortality 36 of 42 (months) Source: Cohen MA, et al. Society of Actuaries 2011 Delayed Word Recall (DWR) and Mortality Cumulative Survival

Cognitive Screening and Mortality 37 of 42 Source: Cohen MA, et al. Society of Actuaries 2011 (months) Enhanced Mental Skills Test (EMST) and Mortality Cumulative Survival

Cognitive Screening and Mortality 38 of 42 Grand Male Female Female Female Female Male Male Male Total Total Total <65 65-69 70+ <65 65-69 70+ Classification EMST EMST EMST EMST EMST EMST EMST EMST EMST Cognitively Impaired 202% 161% 236% 209% 312% 232% 121% 187% 199% Cognitively Intact 98% 101% 97% 87% 97% 112% 95% 100% 108% Grand Male Female Female Female Female Male Male Male Total Total Total <65 65-69 70+ <65 65-69 70+ DWR DWR DWR DWR DWR DWR DWR DWR DWR Cognitively Impaired 178% 163% 190% 107% 150% 231% 108% 136% 191% Cognitively Intact 91% 93% 89% 59% 93% 102% 70% 93% 103% Source: Cohen MA, et al. Society of Actuaries 2011 Relative Mortality Ratios by Age, Gender, Test Sample, and Classification Result

Neuropsychological Testing – Components (Examples) Intellectual functioningWechsler Adult Intelligence Scale (WAIS)Stanford-Binet Intelligence Scale (SBIS)Neuropsychological functioning Orientation – Mini Mental State Exam (MMSE) Language – Boston naming Test (BNT), animal n aming, verbal fluency Visuospatial/Construction – Rey Complex Figure Test (RCFT), Hooper Visual Organization Test (HVOT), Trail A TestAttention/Information Processing – digit span, Stroop Color-Word Test Memory (visual/auditory) – Wechsler Memory Scale Executive Functioning – Wisconsin Card Sorting Test (WCST), clock drawing, Trails B Test Motor Functioning – finger tapping Assessment of mood Beck Depression/Anxiety Inventories (BDI/BAI) Geriatric Depression Scale (GDS) 39 of 42 Source: https ://trans.nih.gov/CEHP/hbpcog-list.htm

Underwriting Approach Remember – chances of cognitive issues increase with agePay close attention to medical record notations:Patient complaints of forgetfulness or memory issues (e.g., missed appointments, birthdays/anniversaries; falling behind at work; need to keep notes) Family or friend comments of forgetfulness or memory issues Consider obtaining a cognitive screening test if not routine Consider requesting neuropsychological testing if situation unclear and looking to offer reconsideration 40 of 42

What We Did Talk About Cognitive impairment represents a decline in cognitive functioning Cognitive impairment may be related to mild cognitive impairment (MCI), dementia, delirium or depressionAlzheimer’s disease (AD) is the most common form of dementia The timeline from pathology to symptoms is insidious and can be decades The primary risk factor for AD is age Both MCI and AD are associated with excess mortality and morbidity Several screening tests are available for use in underwriting Screening tests have been shown to provide mortality risk protectionBeware of medical record comments of forgetfulness and memory loss 41 of 42

42 of 42 Contact Info:Bruce Margolis, DO, MBA AVP, Medical Director Pacific Life bruce.margolis@pacificlife.com 17-73