Potentially inappropriate medication use associated with lower mobility reserve among individuals with preclinical Alzheimer’s disease

Background Falls, a leading cause of disability and mortality in older adults, 1 are associated cognitive impairment and inappropriate medication use. 2 We propose a novel construct, “mobility reserve” (MR), which describes an individual’s resilience against mobility decline. We hypothesize that augmenting MR may delay fall‐associated morbidity. Here, we investigate the association between MR and inappropriate medication use among participants with and without preclinical Alzheimer’s disease (pAD) enrolled in a randomized medication therapy management trial. 3Methods Non‐demented older adults who used ≥1 potentially inappropriate medication 4 were recruited for the RCT. The Medication Appropriateness Index was calculated for all medications (MAI) and for potentially inappropriate medications (MAI‐PIM). Participants’ gait speed (cm/s) was measured under normal conditions and while challenged with 1.5mg of scopolamine to unmask vulnerability. The difference in gait speeds was calculated as mobility reserve change score (MRCS). PET amyloid total brain relative standardized uptake values > 1.4 was used to define pAD. 5 Spearman correlation coefficients (r s ) assessed the relationship between medication appropriateness and MRCS. Results 36 participants were included in this analysis (mean age 75.0 years [SD 6.0]; 78% female); 10 (27.8%) were classified as pAD. The mean (SD) MAI and MAI‐PIM were 10.3 (5.1) and 5.4 (4.0) respectively, not differing by pAD status (p=0.92 and 0.11 for MAI and MAI‐PIM). The mean (SD) MRCS was ‐0.39 cm/s (9.4) (no difference by pAD status; p=0.84). Among those with pAD, MAI and MAI‐PIM were negatively correlated with MRCS (r = ‐0.53 and ‐0.46 respectively), which was not the case among those without pAD (r = 0.37 and 0.34), though a larger sample size is needed to add confidence to these estimates. Conclusion Among community‐dwelling non‐demented older adults, more inappropriate medication use was associated with lower mobility reserve among those with pAD. These results support the hypothesized relationship between MR and medication appropriateness. Future studies should further operationalize measures of MR to open a novel intervention pathway for reducing fall‐related morbidity in cognitively at‐risk populations. References: 1. Katz R, Shah P. JAMA. 2010;303(3):273‐274. 2. Enderlin C et al. Geriatr Nurs. 2015;36(5):397‐406. 3. Moga DC et al. Trials. 2019;20(1):806. 4. American Geriatrics Society. J Am Geriatr Soc. 2015;63(11):2227‐2246. 5.Jack CR et al. Brain. 2015;138(12):3747‐3759.