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Background: Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging.Methods: We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates.Results: At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02).Conclusions: The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection. [ABSTRACT FROM AUTHOR]

Background: Self-reported low physical activity is a defining feature of phenotypic frailty but does not adequately capture physical activity performed throughout the day. This study examined associations between accelerometer-derived patterns of routine daily physical activity and frailty.Methods: Wrist accelerometer and frailty data from 638 participants (mean age 77 [SD = 5.5] years; 44% women) were used to derive 5 physical activity metrics: active minutes/day, sedentary minutes/day, total activity counts/day, activity fragmentation (reciprocal of the average active bout length), and sedentary fragmentation (reciprocal of the average sedentary bout length). Robust, prefrail, and frail statuses were identified using the physical frailty phenotype defined as having 0, 1-2, or ≥3 of the following criterion: weight loss, exhaustion, slowness, self-reported low activity, and weakness. Frailty was collapsed into not frail (robust and prefrail) and frail, and each frailty criteria was dichotomized. Multiple logistic regression was used to model each accelerometer metric. Separate frailty criteria and interactions with age and sex were also examined.Results: With higher amounts and intensity of daily activity (more active minutes, fewer sedentary minutes, higher activity counts) and lower activity fragmentation, the odds of frailty were lower compared to robust/prefrail states (p < .02 for all). For interactions, only an age by sedentary fragmentation interaction on the odds of frailty was observed (p = .01). For each separate criteria, accelerometer metrics were associated with odds of slowness, low activity, and weakness.Conclusion: Less favorable patterns of objectively measured daily physical activity are associated with frailty and the components of slowness, low self-reported activity, and weakness. [ABSTRACT FROM AUTHOR]

Context The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized trial enrolling older adults with low 25-hydroxyvitamin D [25(OH)D], demonstrated vitamin D supplementation ≥ 1000 IU/day did not prevent falls compared with 200 IU/day, with doses ≥ 2000 IU/day potentially showing safety concerns. Objective To examine associations of achieved and change in 25(OH)D concentrations after 3 months of vitamin D supplementation with fall risk. Design Observational analysis of trial data. Setting General community. Participants A total of 637 adults aged ≥ 70 with baseline 25(OH)D concentrations 10 to 29 ng/mL and elevated fall risk. Three-month on-treatment absolute 25(OH)D; absolute and relative changes from baseline. Main Outcome Measures Incident first fall (primary) and first consequential fall (injury or sought medical care) up to 24 months. Cox models were adjusted for sociodemographics, season, Short Physical Performance Battery, and body mass index. Results At baseline, mean (SD) age was 77.1 (5.4) years and 25(OH)D was 22.1 (5.1) ng/mL; 43.0% were women and 21.5% non-White. A total of 395 participants experienced ≥ 1 fall; 294 experienced ≥ 1 consequential fall. There was no association between absolute achieved 25(OH)D and incident first fall (30-39 vs < 30 ng/mL hazard ratio [HR], 0.93; 95% CI, 0.74-1.16; ≥40 vs < 30 ng/mL HR, 1.09; 95% CI, 0.82-1.46; adjusted overall P  = 0.67), nor absolute or relative change in 25(OH)D. For incident consequential first fall, the HR (95% CI) comparing absolute 25(OH)D ≥ 40 vs < 30 ng/mL was 1.38 (0.99-1.90). Conclusion Achieved 25(OH)D concentration after supplementation was not associated with reduction in falls. Risk of consequential falls may be increased with achieved concentrations ≥ 40 ng/mL. Trial Registration ClinicalTrials.gov: NCT02166333 [ABSTRACT FROM AUTHOR]

Background Vitamin D3 supplementation is considered a potential intervention to prevent orthostatic hypotension (OH) based on observational evidence that vitamin D levels are inversely associated with OH. With data from The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a double-blind, randomized, response-adaptive trial, we determined if higher doses of vitamin D3 reduced risk of OH. Methods STURDY tested the effects of higher (1,000+ IU/day, i.e. 1,000, 2,000, and 4,000 IU/day combined) vs. lower-dose vitamin D3 (200 IU/day, comparison) on fall risk in adults ages 70 years and older with low serum 25-hydroxyvitamin D (25(OH)D, 10–29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure (BP). OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg after 1 minute of standing. Participants were also asked about OH symptoms during the assessment and the preceding month. Results Among 688 participants (mean age 77 [SD, 5] years; 44% women; 18% Black), the mean baseline systolic/diastolic BP was 130 (19)/67 (11) mm Hg, serum 25(OH)D was 22.1 (5.1) ng/ml, and 2.8% had OH. There were 2,136 OH assessments over the maximum 2-year follow-up period. Compared with 200 IU/day, 1,000+ IU/day was not associated with seated, standing, or orthostatic BP, and it did not lower risk of OH or orthostatic symptoms. Conclusions These findings do not support use of higher doses of vitamin D3 supplementation as an intervention to prevent OH. Clinical trials registration Trial Number NCT02166333. [ABSTRACT FROM AUTHOR]

Background/objectives: To assess whether vitamin D supplementation prevents specific fall subtypes and sequelae (e.g., fracture). Design Secondary analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You)—a response‐adaptive, randomized clinical trial. Setting: Two community‐based research units. Participants: Six hundred and eighty‐eight participants ≥70 years old with elevated fall risk and baseline serum 25‐hydroxyvitamin D levels of 10–29 ng/ml. Intervention: 200 IU/day (control), 1000 IU/day, 2000 IU/day, or 4000 IU/day of vitamin D3. Measurements Outcomes included repeat falls and falls that were consequential, were injurious, resulted in emergency care, resulted in fracture, and occurred either indoors or outdoors. Results: After adjustment for multiple comparisons, the risk of fall‐related fracture was greater in the pooled higher doses (≥1000 IU/day) group compared with the control (hazard ratio [HR] = 2.66; 95% confidence interval [CI]:1.18–6.00). Although not statistically significant after multiple comparisons adjustment, time to first outdoor fall appeared to differ between the four dose groups (unadjusted p for overall difference = 0.013; adjusted p = 0.222), with risk of a first‐time outdoor fall 39% lower in the 1000 IU/day group (HR = 0.61; 95% CI: 0.38–0.97; unadjusted p = 0.036; adjusted p = 0.222) and 40% lower in the 2000 IU/day group (HR = 0.60; 95%CI 0.38–0.97; p = 0.037; adjusted p = 0.222), each versus control. Conclusion: Vitamin D supplementation doses ≥1000 IU/day might have differential effects on fall risk based on fall location and fracture risk, with the most robust finding that vitamin D doses between 1000 and 4000 IU/day might increase the risk of first time falls with fractures. Replication is warranted, given the possibility of type 1 error. [ABSTRACT FROM AUTHOR]

Background: Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown.Methods: Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age = 77 [SD = 7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: (a) total daily PA minutes and (b) activity fragmentation (mean number of PA bouts / total PA minutes × 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (eg, fragmentation covariate included in the PA minutes model).Results: Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6 [SE = 1.0] and 3.8 [0.9] min/day, respectively; p < .009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (-0.16% [0.05], p = .003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant.Conclusions: Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging. [ABSTRACT FROM AUTHOR]