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• Lesion network mapping identifies functional networks associated with falls risk • WMH-related disruption to the DAN is associated with greater falls risk • WMH-related disruption to the SMN and VAN are associated with foam sway • Physical activity moderates the association between the DAN and falls risk White matter hyperintensities (WMH) are associated with greater falls risk and slow gait speed. Whether these deficits are caused by the disruption of large-scale functional networks remains inconclusive. Further, physical activity moderates the association between WMHs and falls, but whether this extends to the disruption of functional networks remains unknown. One hundred and sixty-four adults (>55 years old) were included in this study. Using lesion network mapping, we identified significant correlations between the percentage of WMH-related disruption of the dorsal attention network and Physiological Profile Assessment (PPA) score (r = 0.24, p < 0.01); and between disruption of both the sensorimotor (r = 0.23, p < 0.01) and ventral attention networks (r = 0.21, p = 0.01) with foam sway. There were no significant associations with floor sway or gait speed. Physical activity moderated the association between the dorsal attention network and PPA score (p = 0.045). Thus, future research should investigate whether physical activity should be recommended in the clinical management of older adults with cerebral small vessel disease. [ABSTRACT FROM AUTHOR]

Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk. Methods: Seventy-six community-dwelling older adults aged 70–80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models. Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (β = −0.26 ± 0.11; p = 0.022) and WMH volume (β = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (β = −0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk. Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA. [ABSTRACT FROM AUTHOR]

Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood.Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD.Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05.Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β  = -0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132).Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function. [ABSTRACT FROM AUTHOR]

Aging is associated with an increased risk of falling. In particular, older adults with mild cognitive impairment (MCI) are more vulnerable to falling compared with their healthy counterparts. Major contributors to this increased falls risk include a decline in dual task performance, gait speed, and postural sway. Recent evidence highlights the potential influence of the default mode network (DMN), the frontoparietal network (FPN), and the supplementary motor area (SMA) on dual task performance, gait speed, and postural sway. The DMN is active during rest and deactivates during task-oriented processes, to maintain attention and stay on task. The FPN and SMA are involved in top-down attentional control, motor planning, and motor execution. The DMN shows less deactivation during task in older adults with MCI. This lack of deactivation is theorized to increase competition for resources between the DMN and task-related brain regions (e.g., the FPN and SMA), increasing distraction from the task and reducing task performance. However, no study has yet investigated the relationship between the between-network connectivity of the DMN with these regions and dual task walking, gait speed or postural sway. We hypothesized that greater functional connectivity both within the DMN and between DMN-FPN and DMN-SMA, will be associated with poorer performance during dual task walking, slower gait speed, and greater postural sway in older adults with MCI. Forty older adults with MCI were measured on a dual taskwalking paradigm, gait speed over a 4-m walk, and postural sway using a sway-meter. Greater within-DMN connectivity was significantly correlated with poorer dual task performance. Furthermore, greater inter-network connectivity between the DMN and SMA was significantly correlated with slower gait speed and greater postural sway on the eyes open floor sway task. Thus, greater resting state DMN functional connectivity may be an underlying neural mechanism for reduced dual task ability, slower gait speed, and greater postural sway, resulting in the increased risk of mobility disability and falling in older adults with MCI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Subtle changes in mobility exist among older adults with mild cognitive impairment (MCI). Life-space mobility defines the frequency and extent of movements in the environment, and lower life-space mobility is associated with adverse health outcomes and MCI. Currently, the underlying mechanism of this association is not well understood. This study examined the functional neural correlates of life-space mobility in community-dwelling older adults with MCI. We first conducted a cross-sectional investigation of the association between resting-state default mode network (DMN) and sensori-motor network (SMN) connectivity and life-space mobility (assessed by the Life-Space Assessment (LSA)) among 60 community-dwelling older adults with MCI using aggregated data from two studies – baseline data from a randomized controlled trial (n = 20) and baseline data from a 12-month prospective study (n = 40). Using data from the 12-month prospective study (n = 35), we then examined whether baseline internetwork connectivity predicts reduced life-space mobility over 12 months. The cross-sectional analysis showed higher DMN-SMN connectivity was associated with lower LSA scores after adjusting for baseline global cognitive function and baseline age (p < 0.01). A significant reduction in LSA scores was observed in the 35 participants of the 12-month prospective study (paired sample t -test mean change = −6.53, p = 0.01). Greater baseline DMN-SMN connectivity was associated with greater reduction in life-space mobility at 12 months (p = 0.04) after adjusting for baseline age, global cognitive function, and LSA score. Our findings suggest that lower and reduced life-space mobility in older adults with MCI may be due to altered functional architecture of the brain such that normal neuro-cognitive motor behaviours may be disrupted. [ABSTRACT FROM AUTHOR]

• Fallers with MCI had a greater level of disruptive DMN-SMN connectivity. • DMN-SMN connectivity increased linearly from Fallers only – MCI only – Fallers + MCI. • Fallers with MCI have significantly greater postural sway than those without MCI. • Postural sway increased linearly from Fallers only - MCI only - Fallers + MCI. Disrupted functional connectivity has been highlighted as a neural mechanism by which impaired cognitive function and mobility co-exist in older adults with mild cognitive impairment (MCI). The objective of this study was to determine the independent and combined effects of MCI and faller status on functional connectivity of three functional networks: default mode network (DMN), fronto-parietal network (FPN) and sensorimotor network (SMN) between 4 groups of older adults: 1) Healthy; 2) MCI without Falls; 3) Fallers without MCI; and 4) Fallers with MCI. Sixty-six adults aged 70–80 years old were included. Cognition was assessed using: 1) cognitive dual task; 2) Stroop Colour-Word Test; 3) Trail Making Tests (TMT); and 4) Digit Symbol Substitution Test (DSST). Postural sway was assessed with eyes opened and standing on the floor. Functional connectivity was measured using fMRI while performing a finger-tapping task. Differences in DMN-SMN connectivity were found for Fallers with MCI vs Fallers without MCI (p =.001). Fallers with MCI had significantly greater postural sway than the other groups. Both DMN-SMN connectivity (p =.03) and postural sway (p =.001) increased in a significantly linear fashion from Fallers without MCI, to MCI without Falls, to Fallers with MCI. Participants with MCI performed significantly worse on the DSST (p =.003) and TMT (p =.007) than those without MCI. Aberrant DMN-SMN connectivity may underlie reduced postural stability. Having both impaired cognition and mobility is associated with a greater level of disruptive DMN-SMN connectivity and increased postural sway than singular impairment. [ABSTRACT FROM AUTHOR]

Exercise plays a key role in healthy aging by promoting both physical and cognitive function. Physical function and cognitive function appear to be interrelated and may share common mechanisms. Thus, exercise-induced improvements in physical function and cognitive function may co-occur and be associated with each other. However, no systematic review has specifically assessed and compared the effects of exercise on both physical function and cognitive function in older adults, and the association between changes in both outcomes after exercise training. Thus, we conducted a systematic review and meta-analysis (N = 48 studies) among older adults (60+ years). These data suggest exercise training has a significant benefit for both physical function (g = 0.39; p < 0.001) and cognitive function (g = 0.24; p < 0.001). At the study level, there was a positive correlation between the size of the exercise-induced effect on physical function and on cognitive function (b = 0.41; p = 0.002). Our results indicate exercise improves both physical and cognitive function, reiterating the notion that exercise is a panacea for aging well. • Maintaining physical and cognitive function is critical for healthy aging. • Physical function and cognitive function are linked and share common mechanisms. • Exercise training improves physical function and cognitive function. • Exercise-induced improvements in physical and cognitive function are associated. [ABSTRACT FROM AUTHOR]