Prevention of Vascular Contributions to Cognitive Impairment and Dementia: The Role of Physical Activity and Exercise.

Vascular contributions to cognitive impairment and dementia, specifically cerebral small vessel disease (CSVD), are the second most common cause of dementia. Currently, there are no specific pharmacological treatments for CSVD, and the use of conventional antidementia drugs is not recommended. Exercise has the potential to prevent and mitigate CSVD-related brain damage and improve cognitive function. Mechanistic pathways underlying the neurocognitive benefits of exercise include the control of vascular risk factors, improving endothelial function, and upregulating exerkines. Notably, the therapeutic efficacy of exercise may vary by exercise type (ie, aerobic versus resistance training) and biological sex; thus, studies designed specifically to examine these moderating factors within a CSVD context are needed. Furthermore, future research should prioritize resistance training interventions, given their tremendous therapeutic potential. Addressing these knowledge gaps will help us refine exercise recommendations to maximize their therapeutic impact in the prevention and mitigation of CSVD.

Myths and Methodologies: Understanding the health impact of head down bedrest for the benefit of older adults and astronauts. Study protocol of the Canadian Bedrest Study.

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Improved intraindividual variability in cognitive performance following cognitive and exercise training in older adults.

OBJECTIVE: Increased intraindividual variability (IIV) of cognitive performance is a marker of cognitive decline in older adults. Whether computerized cognitive training (CCT) and aerobic exercise counteracts cognitive decline by reducing IIV is unknown. We investigated the effects of CCT with or without aerobic exercise on IIV in older adults. METHODS: This was a secondary analysis of an 8-week randomized controlled trial. Older adults (aged 65-85 years) were randomized to CCT alone (n = 41), CCT with aerobic exercise (n = 41), or an active control group (n = 42). The CCT group trained using the Fit Brains® platform 3×/week for 1 hr (plus 3×/week of home-based training). The CCT with aerobic exercise group received 15 min of walking plus 45 min of Fit Brains® 3×/week (plus 3×/week of home-based training). The control group received sham exercise and cognitive training (3×/week for 1 hr). We computed reaction time IIV from the Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test (Flanker), and Pattern Comparison Processing Speed Test (PACPS). RESULTS: Compared with the control group, IIV reduced in a processing speed task (PACPS) following CCT alone (mean difference [95% confidence interval]: -0.144 [-0.255 to -0.034], p < 0.01) and CCT with aerobic exercise (-0.113 [-0.225 to -0.001], p < 0.05). Attention (Flanker congruent) IIV was reduced only after CCT with aerobic exercise (-0.130 [-0.242 to -0.017], p < 0.05). CONCLUSIONS: A CCT program promoted cognitive health via reductions in IIV of cognitive performance and combining it with aerobic exercise may result in broader benefits.

Effect of digital monitoring and counselling on self-management ability in patients with rheumatoid arthritis: a randomised controlled trial.

OBJECTIVES: To assess a remote physiotherapist (PT) counselling intervention using self-monitoring tools for improving self-management ability, physical activity participation, and health outcomes in people with rheumatoid arthritis (RA). METHODS: Eligible participants were randomly assigned to receive group education, a Fitbit®, a self-monitoring app, and PT counselling phone calls (Immediate Group). The Delayed Group received a monthly e-newsletter until week 26, and then the intervention. The primary outcome was Patient Activation Measure (PAM-13). Participants were assessed at baseline, 27 weeks (the primary end point) and 53 weeks. Secondary outcomes included disease activity, pain, fatigue, depression, sitting/walking habits, daily physical activity time, and daily awake sedentary time. Generalized Linear Mixed-effect Models (GLMMs) were used to assess the effect of the intervention on the change of each outcome measure from the initiation to 27 weeks after the intervention. RESULTS: Analysis included 131 participants (91.6% women; 80.2% completed during the COVID-19 pandemic). The mean change of PAM-13 at 27 weeks was 4.6 (SD = 14.7) in the Immediate Group vs -1.6 (SD = 12.5) in the Delayed Group. The mean change in Delayed Group at 53 weeks (after the 26-week intervention) was 3.6 (SD = 14.6). Overall, the intervention improved PAM-13 at 27 weeks post-intervention from the GLMM analysis (adjusted coefficient: 5.3; 95% CI: 2.0, 8.7; p = <0.001). Favourable intervention effects were also found in disease activity, fatigue, depression, and self-reported walking habit. CONCLUSION: Remote counselling paired with self-monitoring tools improved self-management ability in people with RA. Findings of secondary outcomes indicate that the intervention had a positive effect on symptom management.

Sex and BDNF Val66Met polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice.

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus wild-type (Val/Val)) influenced the ability of voluntary running to enhance cognition and hippocampal neurogenesis in mice. Middle-aged C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved performance in both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Premotor and Posterior Parietal Cortex Activity is Increased for Slow, as well as Fast Walking Poststroke: An fNIRS Study.

Methods: Twenty individuals in the chronic stage of stroke walked: (1) at their normal pace, (2) slower than normal, and (3) as fast as possible. Functional near-infrared spectroscopy was used to assess bilateral prefrontal, premotor, sensorimotor, and posterior parietal cortices during walking. Results: No significant differences in laterality were observed between walking speeds. The ipsilesional prefrontal cortex was overall more active than the contralesional prefrontal cortex. Premotor and posterior parietal cortex activity were larger during slow and fast walking compared to normal-paced walking with no differences between slow and fast walking. Greater increases in brain activation in the ipsilesional prefrontal cortex during fast compared to normal-paced walking related to greater gait speed modulation. Conclusions: Brain activation is not linearly related to gait speed. Ipsilesional prefrontal cortex, bilateral premotor, and bilateral posterior parietal cortices are important areas for gait speed modulation and could be an area of interest for neurostimulation.

Can exercise training promote better sleep and reduced fatigue in people with chronic stroke? A systematic review.

Poor sleep and chronic fatigue are common in people with chronic stroke (i.e. ≥ 6 months post-stroke). Exercise training is a viable, low-cost therapy for promoting sleep and reducing fatigue; however, the effects of exercise on sleep and fatigue in people with chronic stroke are unclear. Thus, we conducted a systematic review ascertaining the effects of exercise on sleep and fatigue in people with chronic stroke. We systematically searched EMBASE, MEDLINE, AgeLine, the Cochrane Database of Systematic Reviews, CINAHL, SPORTDiscus, SCOPUS, and reference lists of relevant reviews for articles that examined the effects of exercise on sleep or fatigue in chronic stroke. Search results were limited to adults ≥ 18 years, randomized controlled trials, non-randomized trials, and pre-post studies, which were published in English and examined the effects of exercise on sleep or fatigue in people with chronic stroke. We extracted study characteristics and information on the measurement of sleep and fatigue, and assessed study quality and risk of bias using the CONSORT criteria and Cochrane risk-of-bias tool, respectively. We found two studies that examined the effects of exercise on sleep, and two that examined the effects of exercise on fatigue. All studies reported positive effects of exercise training on sleep and fatigue; however, there were concerns of bias and study quality in all studies. There is preliminary evidence that exercise promotes sleep and reduces fatigue in people with chronic stroke; however, the extent to which exercise impacts these health parameters is unclear.

The independent associations of physical activity and sleep with neural activity during an inhibitory task: cross-sectional results from the MONITOR-OA study.

Sleep and physical activity (PA) are important for the maintenance of executive functions. Whether these lifestyle factors independently contribute to associated neural correlates of executive functions is unknown. We therefore investigated the independent associations of PA and sleep with neural activity during executive performance using task-based functional magnetic resonance imaging (fMRI). Baseline data from a subset of participants (n = 29) enrolled in a randomised trial were used for this cross-sectional analysis. We measured PA, sleep duration and efficiency for 7 days using the SenseWear Mini and examined neural activity underlying response inhibition using the Go/NoGo executive performance task. Brain activation patterns during the NoGo condition were contrasted to activation patterns during the Go condition (i.e., NoGo-Go). We constructed two separate models (controlling for age, sex, and education) to examine the independent associations of (i) PA and sleep duration; and (ii) PA and sleep efficiency with brain activation. Significant clusters were corrected for multiple comparisons (p < 0.05) to determine region-specific activation patterns. The mean (SD) participant age was 61 (9) years, and 79% were female. PA was independently associated with greater task-related blood-oxygen-level dependent (BOLD) signal activity in the left cingulate gyrus; longer sleep duration was independently associated with greater BOLD signal activity in the left putamen. Higher sleep efficiency was independently associated with increased BOLD signal activity in the left hippocampus. PA, sleep duration, and efficiency are each independently associated with greater neural activity underlying response inhibition, which further illustrates that PA and sleep are each uniquely important for brain health.

Importance of characterising sleep breaks within the 24-h movement behaviour framework.

Accelerometers measure the acceleration of the body part they are attached and allow to estimate time spent in activity levels (sedentary behaviour, light, and moderate-to-vigorous physical activity) and sleep over a 24-h period for several consecutive days. These advantages come with the challenges to analyse the large amount of data while integrating dimensions of both physical activity/sedentary behaviour and sleep domains. This commentary raises the questions of 1) how to classify sleep breaks (i.e. wake after sleep onset) during the night within the 24-h movement behaviour framework and 2) how to assess their impact on health while also accounting for night time sleep duration and time in sedentary behaviour and physical activity during the day. The authors advocate for future collaborations between researchers from the physical activity/sedentary behaviour and sleep research fields to ensure appropriate analysis and interpretation of the tremendous amount of data recorded by the newer generation accelerometers. This is the only way forward to provide meaningfully accurate evidence to inform future 24-h movement behaviour guidelines.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Establishing the minimal clinically important difference of the EQ-5D-3L in older adults with a history of falls.

PURPOSE: Establish the minimal clinically important difference (MCID) of a health-related quality of life (HRQoL) measure-the EuroQol EQ-5 Dimensions-3 Level (EQ-5D-3L)-in older adults with a history of falls. METHODS: This study is a secondary analysis of 255 complete cases who were enrolled in a 12-month randomized controlled trial (NCT01029171; NCT00323596); participants were randomized to the Otago Exercise Program (OEP; n = 126/172; Age:81.2 ± 6.2 years; 60.3% Female) or control (CON; n = 129/172; Age:81.7 ± 5.7 years; 70.5% Female). Participants completed the EQ-5D-3L and Visual Analogue Scale (VAS) at baseline and 1-year. The VAS was associated with HRQoL and was the health status anchor (VAS minimal improvement = 7 to 17, maximal improvement ≥ 18, minimal decline = - 7 to - 17, maximal decline ≤ - 18 points). We used four distinct approaches to estimate MCID ranges: (1) anchor-based change differences of the EQ-5D-3L (1-year minus baseline); (2) anchor-based beta coefficients from ordinary least squares regressions (OLS); (3) anchor-based receiver operating characteristic (ROC), and 4) distribution-based standard deviation and standardized effect size of 0.5. RESULTS: EQ-5D-3L MCID ranges for minimal improvements (OEP = 0.028 to 0.059; CON = 0.007 to 0.051), maximal improvements (OEP = 0.059 to 0.090; CON = 0.051 to 0.090), minimal declines (OEP = - 0.029 to - 0.105; CON = - 0.015 to - 0.051), and maximal declines (OEP = - 0.018 to - 0.072; CON = - 0.018 to - 0.082) were established using change difference, OLS, and distribution-based methods. The ROC area under the curve was poor, thus, it was not used to estimate the MCID. CONCLUSIONS: Our results will assist in the interpretation of changes in HRQoL, as measured by the EQ-5D-3L, in older adults with a history of falls.

Baseline health-related quality of life predicts falls: a secondary analysis of a randomized controlled trial.

PURPOSE: Among older adults, health-related quality of life (HRQoL) and falls are associated. Generic patient-reported outcomes measures (PROMs) assess individual's HRQoL. The role for PROMs, a potential tool for predicting subsequent falls, remains under-explored. Our primary aim was to determine whether a baseline PROMs assessment of HRQoL may be a useful tool for predicting future falls. METHODS: A secondary analysis of a 12-month randomized clinical trial (RCT) of a home-based exercise program among 344 adults (67% female), aged ≥ 70 years, with ≥ 1 falls in the prior year who were randomized (1:1) to either a home-based exercise program (n = 172) or usual care (n = 172). A negative binomial regression model with total falls count as the dependent variable evaluated the main effect of the independent variable-baseline HRQoL (measured by the Short-Form-6D)-controlling for total exposure time and experiment group (i.e., exercise or usual care) for the total sample. For the usual care group alone, the model controlled for total exposure time. RESULTS: For the total sample, the rate of subsequent total falls was significantly predicted by baseline HRQoL (IRR = 0.044; 95% CI [0.005-0.037]; p = .004). For the usual care group, findings were confirmed with wider confidence intervals and the rate of prospective total falls was significantly predicted by baseline HRQoL (IRR = 0.025; 95% CI [0.001-0.909]; p = .044). CONCLUSION: These findings suggest the ShortForm-6D should be considered as part of falls prevention screening strategies within a Falls Prevention Clinic setting. 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 .

Minimal Clinically Important Difference of Executive Function Performance in Older Adults Who Fall: A Secondary Analysis of a Randomized Controlled Trial.

INTRODUCTION: Executive function is responsive to exercise and predictive of subsequent falls. Minimal clinically important differences (MCIDs) are critical for understanding whether observed changes are meaningful. However, MCIDs of many cognitive measures are not established. We aimed to determine MCIDs of the Digit Symbol Substitution Test ([DSST] processing speed measure), Stroop (inhibition measure), and Trail Making Test B-A (TMT; set-shifting measure), using anchor- and distribution-based approaches in older adults who have fallen and received the Otago Exercise Program (OEP) relative to usual care only (CON). Our secondary aim was to establish construct (convergent and divergent) validity of these measures. METHODS: Complete case analyses of cognitive outcomes (DSST, Stroop, TMT, and Montreal Cognitive Assessment [MoCA]) were acquired at baseline and 1 year (NCT01029171; NCT003235960); participants were randomized to the OEP (n = 114/172; Age: 80.6 ± 6.1 years; 64.9% Female) or CON (n = 128/172; Age: 82.3 ± 5.8 years; 71.9% Female)]. The MoCA was used as the anchor. We estimated MCIDs using anchor- and distribution-based approaches. Anchor-based executive function change differences ([CD] 1 year minus baseline) observed in participants with meaningful changes in the MoCA (≥3 or ≤ -3 points) receiving the OEP were subtracted from the CON. An anchor-based receiver operator characteristic (ROC) curve was employed to identify optimal cut-off scores of the 3 executive function measures. The distribution-based approach (DA) accounted for variability in baseline and follow-up data. MCID ranges were estimated using these approaches. We used Spearman's correlations to explore convergent validity between executive function measures and other measures involving the same construct (DSST, Stroop, TMT, MoCA, and Mini-Mental State Examination), and divergent validity between executive function measures and variables reflecting different constructs (Geriatric Depression Scale, Instrumental Activities of Daily Living, sex, and body mass index). RESULTS: Based on the 3 approaches, MCID improvement ranges were 3-5 symbols for the DSST (CD = 5; ROC = 2.5; DA = 3.3 symbols), and -11.5 to -26.0 s for the Stroop (CD = -26.0; ROC = -11.5; DA = -20.6 s). MCID decline ranges were -3 to -6 symbols for the DSST (CD = -5.2; ROC = -2.5; DA = -3.3 symbols) and 5.4-30.6 s for the Stroop (CD = 30.6; ROC = 5.4; DA = 20.6 s). MCIDs for the TMT were not meaningful due to high variability (Improvement: CD = -106.6; ROC = -18.4; DA = -69.1 s; Decline: CD = 69.1; ROC = 14.5; DA = 69.1 s). The executive function measures exhibited good convergent (r = -0.22 to r = 0.42) and divergent (r < -0.01 to r = 0.16) validity. CONCLUSIONS: These established MCIDs will allow clinicians to interpret meaningful changes in executive function following exercise amongst older adults who have fallen. The DSST, Stroop, and TMT demonstrated good construct validity, supporting their use in comprehensive fall-risk assessments in older adults who fall.

Sex Differences in Subsequent Falls and Falls Risk: A Prospective Cohort Study in Older Adults.

BACKGROUND: Sex differences for subsequent falls and falls risk factors in community-dwelling older adults who have fallen are unknown. Our aim was to: (1) compare the number of falls between sexes, (2) identify modifiable falls risk factors, and (3) explore the interaction of sex on falls risk factors in older adults who fall. METHODS: Four hundred sixty-two community dwellers seeking medical attention after an index fall were recruited from the Vancouver Falls Prevention Clinic and participated in this 12-month prospective cohort study. Ninety-six participants were part of a randomized controlled trial of exercise. Falls were tracked with monthly falls calendars. Demographics, falls risk measures, and the number of subsequent falls were compared between sexes. A principal component analysis (PCA) was employed to reduce the falls risk measures to a smaller set of factors. The PCA factors were used in negative binomial regression models to predict the number of subsequent falls. Age, exposure time (i.e., number of falls monitoring days), and prescribed exercise (yes/no) were used as covariates, and sex (male/female) and PCA factors were used as main effects. The interaction of sex by PCA factor was then included. RESULTS: Males fell more over 12 months (males: 2.80 ± 6.86 falls; females: 1.25 ± 2.63 falls) than females, and poorer executive function predicted falls in males. Four PCA factors were defined - impaired cognition and mobility, low mood and self-efficacy, mobility resilience, and perceived poor health - each predicted the number of falls. The sex by mobility resilience interaction suggested that mobility resilience was less protective of falls in males. CONCLUSION: Modifiable risk factors related to cognition, physical function, psychological wellbeing, and health status predicted subsequent falls. In males, better mobility was not as protective of falls compared with females. This may be due to males' poorer executive function, contributing to decreased judgement or slowed decision-making during mobility. These results may inform efficacious sex-specific falls prevention strategies.

Effects of exercise training on the cognitive function of older adults with different types of dementia: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of exercise training on the cognitive function of older adults living with different types of dementia, as well as potential moderators of exercise efficacy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Central, PsycINFO, Embase, Medline and CINAHL. ELIGIBILITY CRITERIA: Peer-reviewed, randomised controlled trials, in English (1990-present), which examined the effects of exercise training on the cognitive function of older adults living with dementia. STUDY APPRAISAL AND SYNTHESIS: Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0 and Physiotherapy Evidence Database Scale). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling-Zhang test. RESULTS: Twenty-eight studies (n=2158) were included in the qualitative review and 25 in the meta-analysis. For all-cause dementia, a small effect of exercise training on cognitive function was observed (g=0.19; 95% CI 0.05 to 0.33; p=0.009). Type of dementia and exercise training characteristics did not moderate the effects of exercise training on cognitive function (p>0.05). Adherence to the intervention moderated the cognitive outcome effect size such that greater mean adherence was associated with greater cognitive outcome effect sizes (b=0.02; SE=0.01; p=0.005). CONCLUSION: Exercise training showed small benefits for the cognitive function of older adults living with all-cause dementia. More research and standardised reporting of exercise training characteristics can strengthen the evidence for what works best for which types of dementia. PROSPERO REGISTRATION NUMBER: CRD42020198716.

Sex Differences in the Relationship Between Arterial Stiffness and Cognitive Function in Older Adults.

OBJECTIVE: To examine potential sex differences in the relationship between arterial stiffness and global cognitive function and executive functions. METHODS: Baseline data from 80 older adults were included from two randomized controlled trials (NCT02669394 and NCT02737878). Arterial stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV). Cognitive function assessment included global cognition (Mini-Mental State Examination [MMSE]) and executive functions (set shifting [Trail Making Test Part B minus A], inhibition [Stroop Test], and working memory [Verbal Digit Span Backwards Test]). Separate statistical models were constructed to assess the effect of cf-PWV on each cognitive outcome for females and males. Each statistical model controlled for Framingham cardiovascular disease risk score and education. RESULTS: Higher cf-PWV was associated with impaired MMSE performance in males (ß = -0.48; p = 0.018), but not females (p ≥ 0.389). For executive processes, higher cf-PWV was associated with impaired Trail Making Test Part B minus A (ß = 0.56; p = 0.005) and Stroop Test (ß = 0.59; p = 0.004) in males, but not in females (ps ≥ 0.108). cf-PWV was not significantly associated with Verbal Digit Span Forward minus Backward Test in males or females (ps ≥ 0.108). CONCLUSIONS: Arterial stiffness is more strongly associated with cognitive impairment in males than females. These results further elucidate the interplay between vascular health and cognitive function by providing support for sex-specific mechanisms.

Painting by lesions: White matter hyperintensities disrupt functional networks and global cognition.

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.

Biobehavioral Aspects of the COVID-19 Pandemic: A Review.

OBJECTIVE: This review highlights the scope and significance of the coronavirus disease 2019 (COVID-19) pandemic with a focus on biobehavioral aspects and critical avenues for research. METHODS: A narrative review of the published research literature was undertaken, highlighting major empirical findings emerging during the first and second waves of the COVID-19 pandemic. RESULTS: Interactions among biological, behavioral, and societal processes were prominent across all regions of the globe during the first year of the COVID-19 emergency. Affective, cognitive, behavioral, socioeconomic, and technological factors all played a significant role in the spread of infection, response precautions, and outcomes of mitigation efforts. Affective symptoms, suicidality, and cognitive dysfunction have been widely described consequences of the infection, the economic fallout, and the necessary public health mitigation measures themselves. The impact of COVID-19 may be especially serious for those living with severe mental illness and/or chronic medical diseases, given the confluence of several adverse factors in a manner that appears to have syndemic potential. CONCLUSIONS: The COVID-19 pandemic has made clear that biological and behavioral factors interact with societal processes in the infectious disease context. Empirical research examining mechanistic pathways from infection and recovery to immunological, behavioral, and emotional outcomes is critical. Examination of how emotional and behavioral factors relate to the pandemic-both as causes and as effects-can provide valuable insights that can improve management of the current pandemic and future pandemics to come.