Concomitant Cholinesterase Inhibitor and Anticholinergic Drug Use Among Older Adults With Dementia

Abstract Anticholinergic medications (ACh) are frequently prescribed to older adults despite being associated with impaired physical functioning. Moreover, the concomitant use of ACh and cholinesterase inhibitors (ChEI) reduces the body’s response to both drugs, thereby diminishing the modest effectiveness of ChEI at slowing the progression of dementia symptoms. The objective of this study was to assess the risk of concomitant ACH/ChEI use on functional outcomes, including fall, fracture, and traumatic brain injury (TBI). We conducted a retrospective review of data from the OptumLabs® Data Warehouse, a de-identified administrative claims database for commercially insured and Medicare Advantage (MA) enrollees, representing a diverse mixture of ages, ethnicities, and geographical regions across the U.S. Our cohort included adults 65 and older enrolled in MA between 1998 and 2017. Subjects were required to have dementia (by a diagnosis and/or prescription for a dementia drug (memantine or ChEI)) and at least one claim for ChEI during 12 months of follow-up. Subjects had to be enrolled in MA 6 months prior to the dementia index date. We defined concomitant ACh/ChEI use as an overlap of 30 days or more. Nearly one-third (29%) were concomitantly prescribed ACh and ChEI. Half (51%) of concomitant users were prescribed ChEI first, 46% were prescribed ACh first, and 3% received prescriptions on the same day. Results from multiple logistic regression analyses show that older adults with dementia who had concomitant ACh/ChEI use were 18%, 16%, and 25% more likely to experience a fall, fracture, or TBI, respectively, than those taking ChEI alone.

dementia. Two prospective cross-sectional studies (N = 59; N = 357) were conducted to examine the psychometric properties and clinical utility of myMemCheck®. myMemCheck® evidenced adequate reliability (test-retest, r = 0.67) and strong construct validity (η2 = 0.29, discriminating normal, MCI, dementia). Receiver operating characteristic analysis evidenced an optional myMemCheck® cut score for identifying older adults with MCI or dementia (sensitivity = 0.80, specificity = 0.67, positive predictive value = 0.91, negative predictive value = 0.43). myMemCheck® explained 25% of cognitive status beyond basic patient information. We provide specific suggestions for integrating myMemCheck® into practice to optimize workflow. Study results are further interpreted in the context of two national online surveys (healthcare professionals, N = 181; consumers, N = 1740). Healthcare professionals widely agreed on the need (94%) and importance (86%) of cognitive self-assessments. Public demand for cognitive self-assessment was confirmed by consumers who trialed myMemCheck® as part of their survey participation-86% agreed on the need for a tool like myMemCheck®. Mixed methods findings suggest that myMemCheck® could fast-track the diagnostic process, facilitate appropriate referrals for cognitive and neuropsychological evaluation, reduce assessment burden in healthcare, and prevent negative outcomes associated with undetected cognitive impairment. While quality of life (QOL) is an important endpoint of homecare for persons with dementia (PWD), PWDs often have difficulty in articulating their QOL by themselves. Instead proxy-rating is often used. However, evidence is still scarce regarding to what extent proxy-ratings reflect actual QOL of PWDs. We examined the association between self-report QOL by PWDs and proxy-rated QOL. We conducted a questionnaire survey to PWDs who were 75 years and older, their family, and homecare nurse in charge of the PWD. Two measures were used: 1) a newly developed, 4-item self-report for QOL of PWDs, and 2) a standardized, 6-item proxy-rating dementia QOL scale. In the self-report, the PWD were asked about their daily mood or satisfaction in life in brief, easy-to-understand sentences. The self-reports and proxy-ratings were compared using intraclass correlation coefficients (ICC). Data from 382 PWDs, 248 family caregivers and 124 nurses were used. The mean age of PWD was 85.9 years and 60.5% were female. The proxy-rating by nurses were more strongly associated with self-reports, compared to the association between family proxy rating and self-reports (r = 0.351, p < .001; r = 0.236, p < .001, respectively). Proxy ratings by spouses and biological children were significantly associated with self-report (r = 0.257, p =.004; r =. 204, p = .006, respectively), while rating by children-in-law were not (r = 0.217, p = .160). Proxy-ratings may not be an appropriate substitute for self-report. Homecare nurses may evaluate the QOL of PWD better than their family caregiver. We examined caregiving relationships for individuals with vision impairment (VI) and dementia, using 2011 National Health and Aging Trends Study (NHATS) data, a survey of Medicare beneficiaries, linked to the National Study of Caregiving, a survey of family/unpaid helpers to NHATS participants. VI was defined as self-reported blindness or difficulty recognizing someone across the street, watching television or reading newspaper print. Dementia was defined as probable dementia based on survey-report or AD8 criteria. Caregiving outcomes included: (1) hours of care provided in the last month and (2) number of valued activities affected by caregiving. Among 1,196 caregivers, 617 assisted older adults without dementia or VI (D-/VI-), 298 with dementia but without VI (D+/VI-), 143 without dementia but with VI (D-/VI+), and 138 with dementia and VI (D+/VI+). In fullyadjusted regression models, caregivers of older adults D+/ VI+ spent twice as many hours (IRR=2.0; 95%CI: 1.5-2.7) providing care than caregivers of older adults D-/VI-; however, caregivers of adults D+/VI-and those providing to older adults D-/VI+ spent 1.5-times more hours (95% CI=1.2-1.7; 95% CI=1.1-2.0, respectively). Additionally, caregivers of older adults D+/VI+ reported 4 times as many valued activities were affected (95%CI=2.8-5.6) then caregivers of those D-/VI-, while caregivers of those D+/VI-reported 1.9-times (95% CI=1.3-2.8) and D-/VI+ 1.6-times (95% CI=1.1-2.3) more activities were affected. Our results suggest that caring for older adults with VI has similar demands as caring for older adults with dementia, but that these implications may be magnified when caring for older adults with both dementia and VI.

CONCOMITANT CHOLINESTERASE INHIBITOR AND ANTICHOLINERGIC DRUG USE AMONG OLDER ADULTS WITH DEMENTIA Elizabeth Carter, and Erwin Tan, AARP, Washington, District of Columbia, United States
Anticholinergic medications (ACh) are frequently prescribed to older adults despite being associated with impaired physical functioning. Moreover, the concomitant use of ACh and cholinesterase inhibitors (ChEI) reduces the body's response to both drugs, thereby diminishing the modest effectiveness of ChEI at slowing the progression of dementia symptoms. The objective of this study was to assess the risk of concomitant ACH/ChEI use on functional outcomes, including fall, fracture, and traumatic brain injury (TBI). We conducted a retrospective review of data from the OptumLabs® Data Warehouse, a de-identified administrative claims database for commercially insured and Medicare Advantage (MA) enrollees, representing a diverse mixture of ages, ethnicities, and geographical regions across the U.S. Our cohort included adults 65 and older enrolled in MA between 1998 and 2017. Subjects were required to have dementia (by a diagnosis and/or prescription for a dementia drug (memantine or ChEI)) and at least one claim for ChEI during 12 months of follow-up. Subjects had to be enrolled in MA 6 months prior to the dementia index date. We defined concomitant ACh/ChEI use as an overlap of 30 days or more. Nearly one-third (29%) were concomitantly prescribed ACh and ChEI. Half (51%) of concomitant users were prescribed ChEI first, 46% were prescribed ACh first, and 3% received prescriptions on the same day. Results from multiple logistic regression analyses show that older adults with dementia who had concomitant ACh/ChEI use were 18%, 16%, and 25% more likely to experience a fall, fracture, or TBI, respectively, than those taking ChEI alone.

HIGH OCCURRENCE OF DEMENTIA IN OLDER ADULTS RETURNING TO COMMUNITY FROM PRISON
Amy Byers, 1 Yixia Li, 2 and Lisa Barry, 3 1. University of California,San Francisco / San Francisco VA Health Care System,San Francisco,California,United States,2. Northern California Institute for Research and Education,San Francisco,California,United States,3

. UConn Center on Aging, Farmington, Connecticut, United States
Very little is known about Alzheimer's Disease and related dementias (AD/ADRD) and diseases (e.g., Parkinson's/PD) in older adults returning to community from prison ("older reentry adults"). We utilized a national sample of older veterans to conduct the first study documenting the occurrence (prevalence/incidence) of AD/ADRD and related diseases in older reentry adults. We examined 28,235 reentry veterans who were aged 50 years and older at their most recent release date and Medicare beneficiaries, 2008 through December 31, 2017. AD/ADRD and related diseases were identified by ICD-9/10 codes in the electronic health record from Medicare and inpatient/outpatient Veterans Health Administration data. We examined distributions of AD/ADRD and related diseases across 4 age categories (sample %): 50-64 (55%), 65-74 (37%), 75-84 (7%), and 85+ (0.7%). Of the 28,235 veterans 50 years and older, 17% (n=4,725) had dementia (defined by AD/ADRD based on NIA criteria) or mild cognitive impairment (MCI) and 3% (n=794) had PD. Of those with dementia/MCI, 18% had AD and 26% MCI. Nearly 40% of dementia diagnoses occurred prior to/on most recent release date, and 40% of PD diagnoses occurred prior to/on most recent release date. Differences were significant across age groups (P<.001), with very high rates of diagnoses across all age groups, as well as indicative of high occurrence of early onset dementia and "accelerated aging" [50-64, 14%; 65-74, 18%; 75-84, 33%; and 85+, 53%]. This study is a first step in filling a major research gap by describing AD/ ADRD, MCI and related diseases in reentry adults. Konstantin Arbeev, Olivia Bagley, Arseniy Yashkin, Hongzhe Duan, Igor Akushevich, Svetlana Ukraintseva, and Anatoliy Yashin, Duke University, Durham, North Carolina, United States Large-scale population-based data collecting repeated measures of biomarkers, follow-up data on events (incidence of diseases and mortality), and extensive genetic data provide excellent opportunities for applying statistical models for joint analyses of longitudinal dynamics of biomarkers and time-to-event outcomes that allow investigating dynamics of biomarkers and other relevant factors (including genetic) in relation to risks of diseases and death and how this may propagate to the future. Here we applied one such model, the stochastic process model (SPM), to data on longitudinal trajectories of different variables (comorbidity index, body mass index, cognitive scores), other relevant covariates (including genetic factors such as APOE polymorphisms and polygenic scores, PGS), and data on onset of Alzheimer's disease (AD) in the Health and Retirement Study. We observed that different aging-related characteristics estimated from trajectories of respective variables in SPM are strongly associated with risks of onset of AD and found that these associations differ by sex, APOE status (carriers vs. non-carriers of APOE e4) and by PGS groups. The approach allows modeling and estimating time trends (e.g., by birth cohorts) in relevant dynamic characteristics in relation to the disease onset. These results provide building blocks for constructing the models for forecasting future trends and burden of AD that take into account dynamic relationships between individual trajectories of relevant repeatedly measured characteristics and the risk of the disease. Such models also provide the analytic framework for understanding AD in the context of aging and for finding genetic underpinnings of such links between AD and aging.

CHEMOTHERAPY AND ANESTHESIA IN COLORECTAL CANCER SURVIVORS AND THE RISK OF ALZHEIMER'S DISEASE
Igor Akushevich, 1 Arseniy Yashkin, 1 Julia Kravchenko, 1 and Miklos Kertai, 2 1. Duke University, Durham,North Carolina,United States,2. Vanderbilt University Medical Center,Nashville,Tennessee,United States Exposures common in cancer patients--chemotherapy, surgical injury and/or anesthesia, alone or in combination with predisposing factors--have been suggested as potential risk factors for Alzheimer's disease (AD). We explored the relationship between chemotherapy and cumulative anesthesia exposure, and development of AD in colorectal cancer survivors. We conducted a retrospective cohort study of individuals age 65 and older diagnosed with colorectal cancer between 1998 and 2013, drawing on SEER-Medicare data and employing a proportional hazards model. We found that