Coronary artery disease (CAD) is characterized by endothelial dysfunction, arterial stiffening, and abnormal central hemodynamics, which are independent predictors of adverse cardiovascular events. Dietary nitrate supplementation using beetroot-derived products is a promising strategy, but its vascular effects in adults with CAD remain unclear. This randomized, double-blind, placebo-controlled, crossover pilot trial evaluated the safety, feasibility, and vascular effects of dietary nitrate supplementation to inform the development of a full-scale trial. Eight older adults with confirmed CAD (6 males and 2 females; age 74 [8] years; body mass index 29.2 [5.0] kg·m-2; mean [SD]) were randomized to twice-daily, 2-week supplementation with either nitrate-rich beetroot juice (NRBJ) or nitrate-depleted beetroot juice (NDBJ; placebo). We found that the intervention was well-tolerated, resulting in 100% participant retention, 100% intervention adherence, and no adverse effects requiring medical treatment. Compared to pre-intervention values, brachial artery flow-mediated dilation, expressed as %Δ, improved by 0.98% following NRBJ (90% CI: 0.17 to 1.80), corresponding to a medium-to-large effect size (Hedges' g: 0.72), whereas values remained unchanged following NDBJ (Mean Δ: -0.75%, 90% CI: -1.53 to 0.04). Between-arm comparisons revealed that NRBJ yielded a 1.73% greater improvement in flow-mediated dilation than NDBJ (90% CI: 0.32 to 3.15), representing a medium-to-large effect size (Hedges' g: 0.73). NRBJ resulted in negligible changes in arterial stiffness and hemodynamics. Collectively, these results suggest that dietary nitrate supplementation is highly feasible and well tolerated, and that NRBJ generates promising endothelial effects in older adults with CAD. These findings justify a subsequent, fully powered randomized controlled trial.

Sarcopenia-related traits may be associated with infection-related disease liabilities, but broad phenome-wide genetic screening remains limited. We conducted a two-sample MR-PheWAS of more than 2000 FinnGen R12 phenome-wide endpoints against appendicular lean mass (ALM) and left-hand grip strength (HGS). Multiple testing was controlled using Benjamini-Hochberg false discovery rate (BH-FDR) correction applied separately to 2317 ALM and 2307 HGS primary-estimator tests. Twenty-one ALM endpoints and two HGS endpoints were FDR-significant; the two HGS endpoints were height and weight quantitative traits, and no disease phenotype or infection-related phenotype was FDR-significant for HGS. Among the FDR-significant ALM endpoints, four were infection-related. Rickettsioses were supported by a single instrument and were reported separately, whereas three multi-instrument phenotypes were prioritized for detailed follow-up: postzoster neuralgia, tonsillitis, and sequelae of tuberculosis. On the normalized ALM scale, postzoster neuralgia was associated with higher ALM (IVW beta = 0.01217, P = 1.17 × 10^-4), whereas tonsillitis (beta = -0.02580, P = 1.91 × 10^-4) and sequelae of tuberculosis (beta = -0.01247, P = 2.15 × 10^-4) were associated with lower ALM. Candidate-specific HGS analyses and reverse MR did not show statistically significant associations for these three phenotypes. An exploratory ALM-HGS intersection identified 23 nominally associated disease phenotypes, including five infection-related phenotypes. Exploratory proteomic analyses identified candidate proteins and pathways but did not establish mediation. Overall, the findings indicate phenotype-specific heterogeneity in genetic associations with muscle-related traits and require independent replication.

Wearable devices offer the ability to objectively characterize free-living physical activity; however, raw step-count data generated by commercial devices require systematic processing before they can support rigorous inference. We describe a transparent, reproducible standard operating procedure (SOP) for transforming epoch-level step-count data from commercial Garmin devices into participant-level analytic variables and demonstrate its application in the STRRIDE-PD Reunion study: a long-term follow-up of older adults originally enrolled in a supervised exercise intervention trial. This data pipeline standardizes timestamps, reconstructs daily epoch grids, infers wear time from observed step patterns, and applies a prespecified valid-day threshold (≥10 h inferred wear time) to generate participant-level summaries. Among 67 participants (mean age 71.4 years, 65.7% women), the median valid-day count was 10 days, median average daily steps were 5794, and participant-level estimates were identical across ≥10-h and ≥ 6-h valid-day thresholds. Wearable-derived step counts were significantly associated with 9 of 16 cardiometabolic and fitness outcomes, including cardiorespiratory fitness, body composition, and lipid profiles. By contrast, self-reported exercise - assessed via a frequency-by-duration composite ranked into deciles - was not significantly associated with any outcome. Regression calibration suggested that measurement limitations in self-reported exercise may have contributed to attenuated associations compared with Garmin-derived and calibration-corrected estimates. Limitations include the modest analytic sample size and potential measurement error assumption violations, relatively brief monitoring duration, and indirect wear-time inference. These findings suggest that measurement approach can meaningfully shape physical activity-health conclusions, and that reproducible wearable data pipelines are essential infrastructure for aging epidemiology.

The cerebellum has traditionally been regarded as a brain region primarily involved in motor coordination and balance. However, increasing evidence suggests that the cerebellum plays a significant role in multiple higher-order cognitive functions. This review explores the mechanisms underlying cerebellar involvement in cognitive impairment, focusing on four prevalent cognitive disorders: Alzheimer's disease, vascular cognitive impairment, Parkinson's disease dementia, and frontotemporal dementia. Analysis of existing neuroimaging, neuropathological, and clinical studies indicates that cerebellar structural and functional abnormalities constitute a common pathological feature of cognitive dysfunction in these conditions. Deepening our understanding of cerebellar-cerebral interactions offers new perspectives for early diagnosis, disease monitoring, and therapeutic interventions in cognitive disorders. This review also summarizes research on the cerebellum as a potential target for non-invasive brain stimulation therapy, which holds promise for opening up new avenues for intervention in cognitive disorders and ultimately leading to better treatment outcomes and quality of life for patients.