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Background: Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength.Methods: In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak).Results: The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%.Conclusion: These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life. [ABSTRACT FROM AUTHOR]

Objective ApoE is a well-known gene carrying risk for Alzheimer's disease and is associated with memory performance while the COMT gene is associated with executive functioning but is understudied. The present study investigated these gene interactions across cognitive domains. Method A larger study on gait and aging recruited 89 healthy community-dwelling adults over the age of 60. The primary analyses included 82 participants (67% female, mean age = 74.61, SD = 6.71). The analyses on executive functioning included 72 participants (65% female, mean age = 73.02, SD = 4.99) who completed all measures of interest. ApoE status was defined as presence/absence of Ɛ4. The rs4680 gene on the COMT allele was classified into Val/Met, Val/Val, and Met/Met genotypes. Biological sex was included as a binary term (i.e. male/female). Index variables and age corrected standard scores on the Repeatable Battery for the Assessment of Neuropsychological Status, verbal fluency, and Trail Making Test were included. Results Gene–gene interactions were found for overall cognitive functioning, immediate memory, and semantic fluency. There were main effects of sex for overall cognitive functioning, immediate memory, delayed memory, and semantic fluency. There were main effects for COMT for delayed memory and a main effect for both COMT and ApoE for visuospatial functioning, coding, and verbal fluency (all p's < 0.05). There were no ApoE x COMT x Sex interactions and Trail Making Test B was not related to either gene or sex. Conclusion(s) Our findings suggest that both COMT and ApoE (and their interaction) influence cognition. Future research should investigate gene–gene interactions in larger samples with more comprehensive cognitive batteries. [ABSTRACT FROM AUTHOR]