Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.

Slow walking speed and gait disorders hamper the utility of pedometers for physical activity measurement in frail seniors, such as NH residents, when worn at the usual attachment site. Pedometers, however, can be confidently used with ostensibly healthy older adult populations for both assessment and motivation purposes.

Physical activity has been recognized as an important protective factor reducing disability and mortality and therefore it is focus of many health promotion activities at all ages. More recently a growing body of literature is focusing whether physical activity could also have a positive impact on brain aging with exploring healthy brain aging as well as on cognitive impairment and dementia. An increasing number of prospective studies and randomized controlled trials involving humans take place both with older adults with normal cognition as well as with mild cognitive impairment or dementia. However, the body of evidence is still sparse and many methodological issues make comparisons across studies challenging. Increasingly research into underlying mechanisms in relation to physical activity and brain aging identify biomarker candidates with especially neuroimaging measurements being more used in trials with humans. Whilst the evidence base is slowly growing more detailed research is needed to address methodological issues to finally achieve clinical relevance. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

BACKGROUND AND PURPOSE Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI‐ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS All 36 participants imaged on a Siemens 3.0T Tim Trio. Single‐SE diffusion weighted Echo‐planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI‐ALPS parameter was calculated in these regions and correlated with cognitive status, Mini‐Mental State Examination (MMSE), and ADASCog11 measures. RESULTS Significant correlations were found between DTI‐ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI‐ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION Further work is needed to determine the utility of DTI‐ALPS index in larger elderly cohorts and whether it measures glymphatic activity.

Background: Exercise can modify fall risk factors such as balance and mobility impairments. However, can exercise improve balance confidence? In one strength-training study, researchers reported that a change in balance confidence was not uniformly associated with changes in objective measures of fall risk or physical performance. In fact, some participants’ balance confidence decreased while their physical abilities increased and vice versa. Objective: The aim of this study was to compare changes in balance confidence and balance ability resulting from three exercise interventions (home-based resistance and balance training (RBT), group-based RBT and group-based walking), and the concomitant relationships between change in balance confidence and change in ability. It was hypothesized that participants in the group-based RBT program would improve their balance confidence and performance more than those in the home-based or walking programs. Methods: In a cluster-randomized design, nine retirement villages were assigned to one of the three exercise groups. One hundred and sixty-seven independent-living residents (aged 65–96 years) participated. Each group exercised twice weekly for 20 weeks. Objective balance ability was measured using timed tandem and one-leg stands (static balance), and the 8-foot (2.5 m) up-and-go test (dynamic balance/agility). Balance confidence was assessed using the self-report Activities-specific Balance Confidence (ABC) Scale. Results: Participants in the group-based RBT program improved their static balance scores more than those in the home-based program; however, improvements in balance confidence were greater among participants in the home-based program (all p < 0.05). Discordance between static balance and balance confidence change scores was evident for up to 20% of participants. Change in ABC score was weakly correlated with a change in the up-and-go test score. Conclusions: Exercise training can improve balance confidence and balance ability in retirement village residents. However, as has been shown previously, this study found that exercise interventions may improve balance ability without associated increases in balance confidence and vice versa. Whether the ABC score and balance ability can be enhanced by providing a tailored intervention to improve balance confidence in combination with a RBT program requires further study.