Examining Polypharmacy Status, Associated Symptoms, and the Trajectory of Physical Function and Health Outcomes in Older Adults with and without Alzheimer's Disease and Related Dementias
Authors:   , Coates Martha Caitlin , Coates Martha Caitlin , DiMaria-Ghalili Rose Ann 
Published: August 2023

The purpose of this study was to understand the relationship of symptoms associated with polypharmacy (PPY) vs. no PPY in older adults with and without Alzheimer's Disease and Related Dementias (ADRD) and examine the impact of PPY and individual symptoms on health outcomes and physical function over time in community-dwelling older adults with and without ADRD by the presence of PPY. Polypharmacy, defined as taking five or more medications daily, is a common clinical problem impacting 30% of older adults and as many as 40-70% of those with ADRD. Little is known about symptoms and health outcomes associated with PPY in those with ADRD due to their exclusion from clinical studies resulting in a lack of evidence-based prescribing guidelines to support medication management. This longitudinal case-control study utilized the National Health and Aging Trends Study (NHATS), a nationally representative sample of Medicare beneficiaries who completed surveys from Round 6 to 9 (2016-2019). First, we identified symptoms (depression, anxiety, breathing problems, balance problems, general pain, stomach pain, fatigue, weight loss, insomnia) associated with PPY in those with and without ADRD, and then examined differences in symptom frequency over time in four groups: those with both ADRD and PPY (had both ADRD and PPY), ADRD only (had ADRD but did not have PPY), PPY only (did not have ADRD but did have PPY) and neither ADRD or PPY (N=2,052) . Next, we examined differences in health outcomes (falls, hospitalizations, mortality, and transition to a nursing home) and physical function (Short Physical Performance Battery (SPPB), handgrip strength, assistance with activities of daily living (ADLs)) over time in four groups of older adults: those with both ADRD and PPY, ADRD only, PPY only and neither ADRD or PPY. Lastly, we examined the impact of PPY and each individual symptom on health outcomes (falls, hospitalizations, mortality, and transition to a nursing home) and the trajectory of physical function in those with and without ADRD. Older adults with both ADRD and PPY experienced a mean of 5.06 symptoms over all time points compared to 3.31 (ADRD only), 2.55 (neither ADRD or PPY) and 3.66 (PPY only) (p=<0.001). Symptom frequencies in those with both ADRD and PPY remained higher than all other groups across all four time points. Next, we found that participants with both ADRD and PPY had higher odds of falling in the last year compared to all other groups overtime (Round 6: OR=3.4, 95% CI [1.8,6.3], Round 7: OR=2.3, 95% CI [1.0-5.0], Round 8: OR=3.2, 95% CI [1.4-2.1]), and also experienced more hospitalizations and mortality. Older adults with both ADRD and PPY had lower SPPB scores at baseline and over all four timepoints when compared to all other groups (p=<.001). Those with ADRD (ADRD only and both ADRD and PPY) had lower handgrip scores compared to those without ADRD (PPY only and neither ADRD or PPY) (p=<.001). Those with both ADRD and PPY had higher assistive device utilization and needed more assistance with activities of daily living. Symptoms of PPY were associated with falls, hospitalizations, and nursing home transition. Those with both ADRD and PPY had more symptoms associated with falls and experienced more falls over time than the other groups (ADRD only, PPY only, neither ADRD or PPY). Our study identified the symptoms associated with PPY and its impact on negative health outcomes and physical function decline in older adults with both ADRD and PPY. This research can help inform medication management and support deprescribing practices that improve medication safety and enhance quality of life for older adults living with ADRD.