• Douglas Barthold, Zachary A Marcum, Shuxian Chen, Lindsay White, Nagham Ailabouni, Anirban Basu, Norma B Coe, and Shelly L Gray.
• The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, WA, USA. barthold@uw.edu.
• J Gen Intern Med. 2021 Apr 1; 36 (4): 863868863-868.

BackgroundMedication management requires complex cognitive functioning, and therefore, difficulty taking medications might be an early sign of cognitive impairment and could be a risk factor for Alzheimer's disease and related dementias (ADRD). Accordingly, people with difficulty taking medications may benefit from more detailed cognitive screening, potentially aiding in the diagnosis of ADRD, which is underdiagnosed. We are unaware of evidence on medication management difficulties that precede a real-world ADRD diagnosis in the USA.ObjectiveExamine the association between difficulty taking medications and subsequent real-world ADRD diagnoses.DesignCase-control study, using Health and Retirement Study (HRS) survey data linked to Medicare claims.ParticipantsA total of 1461 HRS respondents with an ADRD diagnosis observed from 1993 to 2012 (cases), matched by year of birth, wave of HRS entry, and sex to 3771 controls with no ADRD diagnosis.Main MeasuresWe examined the association between diagnosis of ADRD and self-reported difficulty taking medications in the preceding years (1-2 and 3-4 years prior to case definition). Control individuals were assigned the index date from their matched case. Conditional logistic regressions adjusted for age, sex, race, education, and comorbidities.Key ResultsCompared with matched controls, cases had higher prevalence of difficulty taking medications 1-2 years prior to diagnosis (11.0% versus 2.3%), and 3-4 years prior to diagnosis (5.8% versus 2.3%). Adjusted analyses showed that compared with individuals without ADRD, those with an ADRD diagnosis had more than four times higher odds of difficulty taking medications 1-2 years prior (OR = 4.56 (CI 3.30-6.31)), and more than two times higher odds of difficulty taking medications 3-4 years prior (OR = 2.41 (CI 1.61-3.59)).ConclusionsOdds of medication difficulty 1-2 years prior were more than four times greater for individuals with ADRD diagnoses compared with those without ADRD. Medication management difficulties may prompt further cognitive screening, potentially aiding in earlier recognition of ADRD.

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