Effect of Medications on Physical Function and Cognition in Nursing Home Residents with Dementia Sarah K. Dutcher, BS,a Gail B. Rattinger, PharmD, PhD,b Patricia Langenberg, PhD,c Pankdeep T. Chhabra, MBBS, MPH,a Xinggang Liu, PhD,d Paul B. Rosenberg, MD,e,f Jeannie-Marie Leoutsakos, MHS, PhD,e,f Linda Simoni-Wastila, BSPharm, PhD,a Loreen D. Walker, BS,a Christine S. Franey, MPH,a and Ilene H. Zuckerman, PharmD, PhDg

OBJECTIVES: To assess the effectiveness of medications used in the management of Alzheimer?s disease and related dementias (ADRD) on cognition and activity of daily liv- ing (ADL) trajectories and to determine whether sex modi- ?es these effects. DESIGN: Two-year (2007?2008) longitudinal study. SETTING: Medicare enrollment and claims data linked to the Minimum Dataset 2.0. PARTICIPANTS: Older nursing home (NH) residents with newly diagnosed ADRD (n = 18,950). MEASUREMENTS: Exposures included four medication classes: antidementia medications (ADMs), antipsychotics, antidepressants, and mood stabilizers. Outcomes included ADLs and cognition (Cognitive Performance Scale (CPS)). Marginal structural models were employed to account for time-dependent confounding. RESULTS: The mean age was 83.6, and 76% of the sam- ple was female. Baseline use of ADMs was 15%, antide- pressants was 40%, antipsychotics was 13%, and mood stabilizers was 3%. Mean baseline ADL and CPS scores were 16.6 and 2.1, respectively. ADM use was not associ- ated with change in ADLs over time but was associated with a slower CPS decline (slope difference: !0.09 points/ year, 99% con?dence interval (CI) = !0.14 to !0.03). Antidepressant use was associated with slower declines in ADL (slope difference: !0.36 points/year, 99%
CI = !0.58 to !0.14) and CPS (slope difference: !0.12 points/year, 99% CI = !0.17 to !0.08). Sex modi?ed the effect of both antipsychotic and mood stabilizer use on ADLs; female users declined most quickly. Antipsychotic use was associated with slower CPS decline (slope differ- ence: !0.11 points/year, 99% CI = !0.17 to !0.06), whereas mood stabilizer use had no effect. CONCLUSION: Despite the observed statistically signi?- cantly slower declines in cognition with ADMs, antidepres- sants, and antipsychotics and the slower ADL decline found with antidepressants, it is unlikely that these bene?ts are of clinical signi?cance. J Am Geriatr Soc 62:1046? 1055, 2014.
Key words: Alzheimer?s disease; dementia; nursing home; psychotropic medication; activities of daily liv- ing; cognition
Thirty percent to 40% of individuals with Alzheimer?s disease and related dementias (ADRDs) in the United States reside in long-term care (LTC) facilities.1 In the nursing home (NH) population, estimates of ADRD prevalence reach 64%.1 Antidementia medications (ADMs), including acetylcholinesterase inhibitors (donepe- zil, galantamine, rivastigmine) and memantine, an N- methyl-D-aspartate receptor antagonist, are commonly used to manage ADRD symptoms and delay declines in cognitive, behavioral, and functional performance.2?5 Although ADMs have been demonstrated to statistically signi?cantly delay cognitive decline in placebo-controlled clinical trials,3?9 effect sizes are modest, and ef?cacy may not translate to clinically meaningful effectiveness.2 To manage behavioral and psychological symptoms of ADRD, individuals often are treated with psychotro- pic medications, including antidepressants, antipsychotics, sedative?hypnotics, and anticonvulsants,10?12 but these agents have received mixed reviews regarding their bene?ts
From the aPharmaceutical Health Services Research Department, School of Pharmacy, University of Maryland Baltimore, Baltimore, Maryland; bPharmacy Practice Division, School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey; cDepartment of Epidemiology and Public Health, School of Medicine, University of Maryland Baltimore, dHospital to Home, Philips Healthcare, eDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center, fDivision of Geriatric Psychiatry and Neuropsychiatry, School of Medicine, The Johns Hopkins University, Baltimore, and gHealth Division, IMPAQ International, Columbia, Maryland. Address correspondence to Ilene H. Zuckerman, Health Division, Impaq International, 10420 Little Patuxent Parkway, Suite 300, Columbia, MD 21044. E-mail: izuckerman@impaqint.com DOI: 10.1111/jgs.12838
JAGS 62:1046?1055, 2014 ? 2014, Copyright the Authors Journal compilation ? 2014, The American Geriatrics Society 0002-8614/14/$15.00
relative to their adverse effects.2,12,13 Greater risks of falls, syncope, and hip fractures have been associated with most psychopharmacological medications,14 acetylcholinesterase inhibitors,15 and antidepressants, respectively.16 Further- more, use of antipsychotics has been associated with greater mortality17,18 and poorer cognition.19 Signi?cant changes in treatment that individuals with dementia experience as they transition into a NH setting,20 as well as differences in their drug receipt once residing in NHs,10,11 demonstrate the important treatment decisions that clinicians must make in the face of advancing disease progression. ADRD symptom presentation varies according to sex. One study found clinical disease development to be more likely in women with Alzheimer?s disease (AD) pathology than in men.21 Men often display more physically aggres- sive, apathetic, and regressive behaviors, whereas women tend to demonstrate depression, anxiety, and agitation through verbal means.22,23 However, little is known about sex differences in response to ADMs24,25 or psychopharma- cological medications, with one study reporting sex differ- ences in responses of individuals with AD to sertraline.26 Given the high prevalence of medication use in NH residents with ADRD,10?12 questions about ef?cacy and adverse events, differential symptom expression between the sexes, and the paucity of information regarding hetero- geneity in treatment effectiveness, investigation is war- ranted to identify NH residents with ADRD who are most likely to realize bene?ts from medications used to manage ADRD symptoms. This study sought to measure the asso- ciations between medications commonly used in ADRD management and ADL functioning and cognition over time in NH residents and whether the associations between these medications and functional and cognitive outcomes vary by sex.