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Background: Anticholinergic medications are associated with fall risk. Higher dopaminergic signaling may provide resilience to these effects. We tested interactions between anticholinergic medication use and dopaminergic genotype on risk for recurrent falls over 10 years.Methods: Participants in the Health, Aging, and Body Composition (Health ABC) study (n = 2 372, mean age = 73.6; 47.8% men; 60.0% White) without disability or anticholinergic use at baseline were followed for up to 10 years for falls. Medication use was documented in 7 of 10 years. Highly anticholinergic medications were defined by Beers criteria, 2019. Recurrent falls were defined as ≥2 in the 12 months following medication assessment. Generalized estimating equations tested the association of anticholinergic use with recurrent falls in the following 12 months, adjusted for demographics, health characteristics, and anticholinergic use indicators. Effect modification by dopaminergic genotype (catechol-O-methyltransferase [COMT]; Met/Met, higher dopamine signaling, n = 454 vs Val carriers, lower dopamine signaling, n = 1 918) was tested and analyses repeated stratified by genotype.Results: During follow-up, 841 people reported recurrent falls. Anticholinergic use doubled the odds of recurrent falls (adjusted odds ratio [OR] [95% CI] = 2.09 [1.45, 3.03]), with suggested effect modification by COMT (p = .1). The association was present in Val carriers (adjusted OR [95% CI] = 2.16 [1.44, 3.23]), but not in Met/Met genotype (adjusted OR [95% CI] = 1.70 [0.66, 4.41]). Effect sizes were stronger when excluding baseline recurrent fallers.Conclusion: Higher dopaminergic signaling may provide protection against increased 12-month fall risk from anticholinergic use. Assessing vulnerability to the adverse effects of anticholinergic medications could help in determination of risk/benefit ratio for prescribing and deprescribing anticholinergics in older adults. [ABSTRACT FROM AUTHOR]

Background: Mild parkinsonian signs (MPS), highly prevalent in older adults, predict disability. It is unknown whether energy decline, a predictor of mobility disability, is also associated with MPS. We hypothesized that those with MPS had greater decline in self-reported energy level (SEL) than those without MPS, and that SEL decline and MPS share neural substrates.Method: Using data from the Health, Aging and Body Composition Study, we analyzed 293 Parkinson's disease-free participants (83 ± 3 years old, 39% Black, 58% women) with neuroimaging data, MPS evaluation by Unified Parkinson Disease Rating Scale in 2006-2008, and ≥3 measures of SEL since 1999-2000. Individual SEL slopes were computed via linear mixed models. Associations of SEL slopes with MPS were tested using logistic regression models. Associations of SEL slope with volume of striatum, sensorimotor, and cognitive regions were examined using linear regression models adjusted for normalized total gray matter volume. Models were adjusted for baseline SEL, mobility, demographics, and comorbidities.Results: Compared to those without MPS (n = 165), those with MPS (n = 128) had 37% greater SEL decline in the prior 8 years (p = .001). Greater SEL decline was associated with smaller right striatal volume (adjusted standardized β = 0.126, p = .029). SEL decline was not associated with volumes in other regions. The association of SEL decline with MPS remained similar after adjustment for right striatal volume (adjusted odds ratio = 2.03, 95% CI: 1.16-3.54).Conclusion: SEL decline may be faster in those with MPS. Striatal atrophy may be important for declining energy but does not explain the association with MPS. [ABSTRACT FROM AUTHOR]

Background and Purpose: Mild Parkinsonian signs (MPS) are common in older adults. We hypothesized that MPS are associated with lower functional connectivity (FC) in dopamine‐dependent cortico‐striatal networks, and these associations vary with white matter hyperintensity (WMH), a risk factor for MPS. Methods: We examined resting‐state functional MRI in 266 participants (mean age 83; 57% female; 41% African American) with data on MPS (Unified Parkinson's Disease Rating Scale), demographics, cognition, muscle‐skeletal, and cardiometabolic health. FC between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with MPS, adjusted for covariates. Interactions of FC by WMH were tested; and analyses were repeated stratified by WMH above/below the median. Results: Compared to those without MPS, those with MPS had lower cortico‐striatal FC in the left executive network (adjusted odds ratio [95% confidence interval], p‐value: 0.188 [0.043, 0.824],.027). The interaction with WMH was p =.064; left executive FC was inversely associated with MPS for high WMH (0.077 [0.010, 0.599],.014) but not low WMH participants (1.245 [0.128, 12.132],.850). Conclusions: MPS appear related to lower executive network FC, robust to adjustment for other risk factors, and stronger for those with higher burden of WMH. Future longitudinal studies should examine the interplay between cerebral small vessel disease and connectivity influencing MPS. [ABSTRACT FROM AUTHOR]