White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p<.001) and ventral attention network (p <. 001) was significantly correlated with MoCA score. Thus, the greater the disruption to the sensorimotor and ventral attention networks, the poorer the global cognition. Our results reveal that the visual, ventral attention, and frontoparietal networks are most vulnerable to disruptions stemming from WMHs. Additionally, we identified that disruption to the sensorimotor and ventral attention networks, as a result of WMHs, may underlie deficits in global cognition in older adults with cerebral small vessel disease.

Background: Frailty is a dynamic geriatric syndrome associated with adverse health outcomes, yet its progression can be mitigated through targeted interventions. Objective: This study aimed to investigate predictors of frailty transitions in Chinese older adults, focusing on physical activity (PA) and physical function. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we examined transitions between frailty states (robust, prefrail, and frail) from 2011 (baseline) to 2013 (follow-up) among 1014 participants aged 65 years and older. The following outcomes were assessed, including frailty using the physical frailty phenotype, PA using a modified International Physical Activity Questionnaire, and physical function using the Short Physical Performance Battery (SPPB) and handgrip strength. Ordinal logistic regression models were used to examine the relationship between PA, physical function, and frailty transitions. Results: Results showed that higher PA levels and better physical function reduced the likelihood of worsening frailty or increased the probability of transitioning to robustness. Key findings from the subgroup include: among robust individuals, greater handgrip strength predicted maintained robustness (average marginal effects [AME]=1.12%; P =.02); in prefrail individuals, higher vigorous PA (AME=21.76%; P =.04) and handgrip strength (AME=0.64%; P =.003) increased transitions to robustness; for frail individuals, increased low-intensity PA (AME =22.48%; P =.04) and higher SPPB walking subscores (AME=27.73%; P =.02) promoted improvement to nonfrailty. Conclusions: These findings highlight the importance of tailored interventions based on baseline frailty status. Promoting PA and improving physical function, particularly muscle strength and mobility function, may help delay or reverse frailty progression.

Objective: Using stratified analyses, we examined the cost-effectiveness of the Otago Exercise Programme (OEP), from a health care system perspective, among older women and men who have previously fallen. Methods: This study was a secondary stratified analysis (by women and men), of a 12-month prospective economic evaluation of a randomized clinical trial (OEP compared with usual care). Three hundred and forty four community-dwelling older adults (≥70; 172 OEP (110 women; 62 men), 172 usual care (119 women; 53 men)) who sustained a fall in the past 12 months and received a baseline assessment at the Vancouver Falls Prevention Clinic, Canada were included. A gender by OEP/usual care interaction was examined for the falls incidence rate ratio (IRR). Outcome measures stratified by gender included: falls IRR, incremental cost-per fall prevented (ICER), incremental cost per quality adjusted life year (QALY, ICUR) gained, and mean total health care resource utilization costs. Results: Men were frailer than women at baseline. Men incurred higher mean total healthcare costs $6794 (SD: $11906)). There was no significant gender by OEP/usual care interaction on falls IRR. The efficacy of the OEP did not vary by gender. The adjusted IRR for the OEP group demonstrated a 39% (IRR: 0.61, CI: 0.40–0.93) significant reduction in falls among men but not women (32% reduction (IRR: 0.69, CI: 0.47–1.02)). The ICER showed the OEP was effective in preventing falls and less costly for men, while it was costlier for women by $42. The ICUR showed the OEP did not impact quality of life. Conclusion: Future studies should explore gender factors (i.e., health seeking behaviours, gender related frailty) that may explain observed variation in the cost-effectiveness of the OEP as a secondary falls prevention strategy. Trial registrations: ClinicalTrials.gov Protocol Registration System Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596

Cognitive frailty is characterized by concurrent physical frailty and mild cognitive impairment and is associated with increased risk of falls. Exercise is an evidence-based strategy to prevent falls, but whether exercise reduces falls in people with cognitive frailty is unknown. We examined the effects of home-based exercise on subsequent falls among community-dwelling older adults with cognitive frailty who have previously fallen. A sub-group analysis of a 12-month, single-blind, randomized controlled trial among 344 adults aged 70 years or more who had fallen within the past 12 months. Participants were randomized to either 12 months of home-based exercise (n=172) or usual care (n=172). In this sub-analysis, we included 192 participants with cognitive frailty (home-based exercise=93; usual care=99) with Short Physical Performance Battery scores ≤9/12 and Montreal Cognitive Assessment scores <26/30. Our primary analysis examined the effect of exercise on self-reported falls rate over 12 months. Secondary analyses investigated the intervention's effects on scores on the Short Physical Performance Battery and the Montreal Cognitive Assessment. We also explored whether greater than or equal to mean average monthly adherence (i.e., ≥45.5%) moderated treatment effects. At 12 months, falls rates were 35% lower in the home-based exercise group compared with the usual care group (IRR=0.65; p=0.042). Score on the Short Physical Performance Battery significantly improved among home-based exercise participants with greater than or equal to mean adherence vs. those with less than mean adherence (estimated mean difference: 0.94; p=0.022). Exercise is a promising strategy for reducing subsequent falls in people with cognitive frailty. Greater exercise adherence improved physical function in this population. gov identifier: NCT01029171.

Objectives: Physical frailty is associated with increased risk of cognitive impairment. However, its impact on sustained cognitive processing as evaluated by intraindividual variability (IIV), and factors beneficial to IIV in physically frail older adults remain unexplored. This study aimed to quantify differences in IIV between older adults with and without physical frailty, and examine whether education facilitated maintenance of IIV. Methods: This cross-sectional study included 121 community-dwelling older adults 65-90 years with/without physical frailty (PF and non-PF; n = 41 and n = 80 respectively). Physical frailty was determined via Short Physical Performance Battery. Dispersion across the seven components of the Montreal Cognitive Assessment (MoCA) was computed to ascertain IIV. Multivariate analysis of covariance was used to determine group differences in total score and IIV. Four moderation models were constructed to test the effects of education on age-total score and age-IIV relationships in PF and non-PF. Results: Compared with non-PF, PF showed greater IIV (p = .022; partial η² = 0.044). Among PF, education moderated age-total score (R-sq = 0.084, F = 5.840, p < 0.021) and age-IIV (R-sq = 0.101, F = 7.454, p = 0.010) relationships. IIV increased with age for those with five years (β = 0.313, p = 0.006) or no formal education (β = 0.610, p = 0.001). Greater than seven years of education (β = 0.217, p = 0.050) may be required to maintain IIV at older age. Conclusion: IIV may be a sensitive method to differentiate physically frail older adults. Additionally, perceived cognitive benefits of education may be dependent on physical functioning.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one’s capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions—eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks—frontoparietal network (FPN) and default mode network (DMN)—significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.