Cognitive reserve proxies are associated with age-related cognitive decline - Not age-related gait speed decline.

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life.

Gait in cerebral small vessel disease, pre-dementia, and dementia: A systematic review.

BACKGROUND: The interrelationships between gait, cerebral small vessel disease (CSVD), and cognitive impairments in aging are not well-understood-despite their common co-occurrence. OBJECTIVE: To systematically review studies of gait impairment in CSVD, pre-dementia, and dementia, and to identify key gaps for future research and novel pathways toward intervention. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search strategy was implemented in PubMed to identify relevant studies. Potential articles (n = 263) published prior to 1 December 2021 were screened by two reviewers. Studies with sample sizes >20 and including some adults over > 65 years (n = 202) were included. RESULTS: The key findings were that (1) adverse gait and cognitive outcomes were associated with several (rather than select) CSVD pathologies distributed across the brain, and (2) poor gait and CSVD pathologies were more strongly associated with dementia with a vascular, rather than an Alzheimer's disease-related, cause. DISCUSSION: A better understanding of the interrelationships between gait performance in CSVD, pre-dementia, and dementia requires studies examining (1) comprehensive patterns in the clinical manifestations of CSVD, (2) racially/ethnically diverse samples, (3) samples followed for extended periods of time or across the adult life span, (4) non-traditional CSVD neuroimaging markers (e.g. resting-state functional magnetic resonance imaging (fMRI)), and (5) continuous (e.g. wearable sensors) and complex (e.g. dual-task) walking performance.

Randomized Controlled Trial of Social Ballroom Dancing and Treadmill Walking: Preliminary Findings on Executive Function and Neuroplasticity From Dementia-at-Risk Older Adults.

This randomized controlled trial (NCT03475316) examined the relative efficacy of 6 months of social ballroom dancing and treadmill walking on a composite executive function score, generated from digit symbol substitution test, flanker interference, and walking while talking tasks. Brain activation during functional magnetic resonance imaging (fMRI) versions of these executive function tasks were secondary outcomes. Twenty-five dementia-at-risk older adults (memory impairment screen score of ≥3 to ≤6 and/or an Alzheimer's disease-8 Dementia Screening Interview of ≥1) were randomized in June 2019 to March 2020-16 completed the intervention before study termination due to the COVID-19 (eight in each group). Composite executive function scores improved post-intervention in both groups, but there was no evidence for between-group differences. Social dancing, however, generated greater improvements on digit symbol substitution test than treadmill walking. No intervention-related differences were observed in brain activation-although less hippocampal atrophy (tertiary) was observed following social dancing than treadmill walking. These preliminary findings are promising but need to be confirmed in future large-scale and sufficiently powered randomized controlled trials.

Age-related changes in gait domains: Results from the LonGenity study.

BACKGROUND: Impairment in gait domains such as pace, rhythm, and variability are associated with falls, cognitive decline, and dementia. However, the longitudinal changes in these gait domains are poorly understood. The aim of this study was to examine age-related changes in gait domains overall and in those with cognitive impairment and mobility disability. METHODS: Participants were from the LonGenity study (n = 797; M Age=75.1 SD 6.5 years; 58.2% female) and were followed up to 12 years (Median=3.3; IQR: 1.1; 6.3). Gait speed and absolute values of step length, step time, cadence and, variability (standard deviation) of step length and step time during usual pace walking were assessed. Principal components analysis was used to obtain weighted combinations of three gait domains: pace (velocity, step length), variability (step length variability, step time variability) and rhythm (step time). Linear mixed effect models were used to examine age-related changes in gait domains overall, and in those with cognitive impairment and mobility disability at baseline. RESULTS: Pace declined, and rhythm increased (worsened) in an accelerating non-linear fashion. Variability gradually increased with age. Those with cognitive impairment had faster rates of change in pace and rhythm. Those with mobility disability had faster increases in rhythm. CONCLUSIONS: Age-related changes in gait domains are not uniform. Individuals with cognitive and mobility impairments are particularly vulnerable to accelerated change in pace and or rhythm.

The Role of Daily Step Count in Determining Risk Factors for Falls.

Falls risk is often assessed without considering exposure to risk. We examined the risk factors associated with falls in those with greater and lower levels of daily step count. Falls were recorded over 12 months using bimonthly calendars in community-dwelling older people (mean age 72.0, SD 6.9). Daily step count was measured using a pedometer worn consecutively for 7 days. A cut score of <5,575.5 steps/day was used to identify people with lower step count. Negative binominal models were used to identify cognitive, medical, and sensorimotor factors associated with falls in those with higher versus lower levels of daily step count. In those with lower daily step count, poorer executive function, slower gait speed, and lower steps per day were associated with increased falls risk. In those with higher step count, only mood was associated with increased falls risk. Considering daily step count is important when assessing falls risk in older people.

Longitudinal Associations Between Falls and Risk of Gait Decline: Results From the Central Control of Mobility and Aging Study.

OBJECTIVE: To examine whether falls are associated with longitudinal changes in different gait domains and onset of clinical gait abnormalities. DESIGN: Longitudinal study. SETTING: General community. PARTICIPANTS: Ambulatory older adults free of dementia (N=428; mean age, 77.8±6.4 years). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait was assessed with a computerized walkway. Pace, rhythm, and variability (outcome measures) were derived from individual gait measures, using principal component analysis. Clinical gait abnormalities (neurologic, nonneurologic, mixed) were visually assessed by clinicians. Linear mixed-effects models were used to examine the associations between falls (the exposure variable coded as none, single, and multiple) and changes in gait domains. Multinomial logistic regression was used to examine associations between falls and the onset of clinical gait abnormalities. Models were adjusted for sex, education, age, body mass index, number of comorbidities, gait speed at the first follow-up, and time between the last fall and the first follow-up gait assessment. RESULTS: Pace declined while rhythm and variability increased at a faster rate (P<.05) among 32 participants with multiple falls in the first year of follow-up compared with 299 participants with no falls. Risk for clinical gait abnormalities between those with no falls, a single fall, or multiple falls was not different. CONCLUSIONS: Multiple falls predict future gait decline in multiple domains in aging. Interventions to prevent gait decline after multiple falls should be investigated.

Cognitive inhibition tasks interfere with dual-task walking and increase prefrontal cortical activity more than working memory tasks in young and older adults

BACKGROUND: Prior work suggests there may be greater reliance on executive function for walking in older people. The pre-frontal cortex (PFC), which controls aspects of executive function, is known to be active during dual-task walking (DTW). However, there is debate on how PFC activity during DTW is impacted by ageing and the requirements of the cognitive task. RESEARCH QUESTION: Functional near infrared spectroscopy, was used to investigate how PFC activity during walking was affected by (i) healthy ageing; and (ii) dual-tasks that utilise inhibition or working memory aspects of executive function. METHODS: Young (n = 26, 16 females, mean 20.9 years) and older (n = 26, 16 females, mean 70.3 years) adults performed five conditions: normal walking; Reciting Alternate Letters of the alphabet (RAL, requiring cognitive inhibition and working memory) during standing and walking; and serial subtraction by threes (SS3, requiring working memory alone) during standing and walking. Walking speed, cognitive performance, the PFC haemodynamic response, and fear of falling ratings were analysed using linear mixed-effects modelling. RESULTS: Compared to quiet standing, PFC activity increased during normal walking for older adults but decreased for young adults (p < 0.01). Across both groups, fear of falling contributed to higher PFC activity levels when walking (p < 0.01). PFC activity increased during DTW, and this increase was greater when performing RAL compared to the SS3 task (p < 0.01). Although the rate of correct responses was higher for RAL, walking speed reduced more with RAL than SS3 in the young group (p = 0.01), and the rate of correct responses reduced more when walking with RAL than SS3 in the older group (p < 0.01). SIGNIFICANCE: Older adults have increased levels of PFC activation during walking compared to younger adults and fear of falling is a cofounding factor. The interference between gait and a concurrent cognitive task is higher when the cognitive task requires inhibition.

Risk factors for decline in gait speed during walking while talking in older adults.

BACKGROUND & AIMS: Slow gait speed during Walking While Talking (walking while reciting alternate letters of the alphabet; WWT) is associated with an increased risk of developing dementia and falls. The aim of this study was to examine longitudinal changes in WWT-speed and to identify risk factors that may modify the rate of change in WWT-speed. METHODS: A total of 431 older participants (55.7% female; M Age=76.8 ± 6.4 years; mean follow up 2.1 ± 1.8 years) enrolled in the Central Control of Mobility in Aging study were examined. WWT-speed (cm/s) was measured with a computerized walkway. The following baseline measures were examined as risk factors: demographics [age, sex, education], medical illnesses [hypertension, diabetes, cardiac arrhythmias, history of stroke, Parkinson's disease, kidney disease, arthritis], cognitive functions [global cognition, executive function, processing speed], physical and sensory functions [unipedal stance time, gait speed during single task walking, visual acuity], psychological variables [depression, anxiety] and falls. Linear mixed effect models were used to examine 1) change in WWT-speed over time, and 2) risk factors associated with change in WWT-speed over time. RESULTS: WWT-speed declined in an accelerating non-linear fashion over time after adjusting for baseline age, sex and education. The rate of decline in WWT-speed was modified by older age (b -0.16 95%CI -0.22, -0.09), poorer balance (b -1.73 95%CI -2.57, -0.90), and faster gait speed during single task walking (b -0.06 95%CI -0.08, -0.04). SIGNIFICANCE: This study identified fixed and modifiable risk factors of faster decline in WWT-speed over time in community-residing older adults.

Longitudinal associations between falls and future risk of cognitive decline, the Motoric Cognitive Risk syndrome and dementia: the Einstein Ageing Study.

BACKGROUND: falls share risk factors with cognitive decline but whether falls predict cognitive decline, pre-dementia syndromes and dementia is poorly understood. OBJECTIVES: this study aimed to examine if falls are associated with cognitive decline in specific domains and the risk of Motoric Cognitive Risk (MCR) syndrome and dementia. DESIGN: cross-sectional study. METHODS: in older people (age 80.6 ± 5.3 years) free of dementia at baseline, the number of falls (none, one or multiple) during the year before enrolment and the first year of follow-up (exposure) were recorded. Decline in specific cognitive functions (global cognition, episodic verbal memory, verbal fluency, working memory, response inhibition and processing speed-attention), incident MCR and incident dementia were outcome measures. Linear mixed effects models were used to examine the associations between falls and cognitive decline, adjusting for confounders. Cox proportional hazards models were used to determine if falls predicted risk of incident MCR or dementia. RESULTS: of 522 eligible participants, 140 had a single fall and 70 had multiple falls. Multiple falls were associated with a greater decline in global cognition, episodic memory, verbal fluency and processing speed-attention compared to those with no falls (P < 0.05). Over a median follow-up of 1.0 years 36 participants developed MCR and 43 participants developed dementia. Those with multiple falls had a two-fold increased risk of MCR compared to those with no falls, but no increased risk of developing dementia. CONCLUSIONS: multiple falls may be an important marker to identify older people at greater risk of future cognitive decline and incident MCR.

Relative Trajectories of Gait and Cognitive Decline in Aging.

BACKGROUND: Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood-particularly among those with the motoric cognitive risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. METHODS: We examined gait and cognitive functions of 1 095 LonGenity study participants (mean age = 75.4 ± 6.7 years) with up to 12 years of annual follow-up. Participants were of Ashkenazi Jewish descent, free of dementia, ambulatory, and had a 12.2% MCR prevalence at baseline. Gait speed was measured at usual pace walking (single-task walking, STW-speed) and walking while talking (WWT-speed). Eleven neuropsychological test scores were examined separately, and as a global cognition composite. Linear mixed-effects models adjusted for baseline sex, education, parental longevity, cognitive impairment, and global health were used to estimate changes in gait and cognition, as a function of age and MCR. RESULTS: STW-speed, WWT-speed, and cognitive tests performance declined in a nonlinear (accelerating) fashion with age. STW-speed declined faster than WWT-speed and cognitive test scores. People with MCR showed faster rates of decline on figure copy and phonemic fluency. CONCLUSIONS: Gait declines at a faster rate than cognition in aging. People with MCR are susceptible to faster decline in visuospatial, executive, and language functions. This study adds important knowledge of trajectories of gait and cognitive decline in aging, and identifies MCR as a risk factor for accelerated cognitive decline.

The association between simple reaction time variability and gait variability: The Tasmanian Study of Cognition and Gait.

INTRODUCTION: Greater double support time (DST) variability is associated with falls and memory decline. The underlying neurophysiological mechanisms of DST variability are poorly understood. Simple reaction time (SRT) variability, a measure of attention-processing speed is associated with falls and dementia and, may underlie greater DST variability. The aims of this study were to examine the association between SRT and DST variability and if SRT variability mediates the associations between poorer cognition/brain structure and DST variability. METHODS: Participants (n = 408) were community-dwelling older people without dementia (mean age 72.0 ± 7.0). DST variability was the standard deviation (SD) of DST, assessed with a walkway and averaged across steps of 6 walks. SRT variability was the SD of a button pressing task in response to a visual stimulus. Executive function and processing speed were assessed with neuropsychological tests. Magnetic Resonance Imaging was used to obtain cortical thickness (total and in frontal regions) and cerebral small vessel disease (cSVD). Multivariable linear regression models were used to examine the association between SRT and DST variability and if SRT variability mediated any associations of cognition/brain structure with DST variability. RESULTS: Greater SRT variability was associated with greater DST variability (p = 0.002). SRT variability partially mediated the association between poorer executive function and greater DST variability. Smaller mean thickness in orbitofrontal regions and greater cSVD burden were only associated with DST variability (p < 0.05), not with SRT variability (p > 0.05). CONCLUSIONS: Greater SRT variability, which may occur due to inefficient executive functioning, could be an underlying neurophysiological mechanism of greater DST variability.

A novel cognitive-motor exercise program delivered via a tablet to improve mobility in older people with cognitive impairment - StandingTall Cognition and Mobility.

BACKGROUND: Evidence-based interventions to improve mobility in older people include balance, strength and cognitive training. Digital technologies provide the opportunity to deliver tailored and progressive programs at home. However, it is unknown if they are effective in older people, especially in those with cognitive impairment. OBJECTIVE: The aim of this study was to examine the efficacy of a novel tablet-delivered cognitive-motor program on mobility in older people with cognitive impairment. METHODS: This was a 6-month single-blind randomised controlled trial of older people living in the community with subjective and/or objective cognitive impairment. Participants randomised to the intervention were asked to follow a 120 min per week balance, strength and cognitive training program delivered via an app on an iPad. Both the intervention and control group received monthly phone calls and health fact sheets. The primary outcome measure was gait speed. Secondary measures included dual-task gait speed, balance (step test, FISCIT-4), 5 sit to stand test, cognition (executive function, memory, attention), mood and balance confidence. Adherence, safety, usability and feedback were also measured. RESULTS: The planned sample size of 110 was not reached due to COVID-19 restrictions. A total of 93 (mean age 72.8 SD 7.0 years) participants were randomised to the two groups. Of these 77 participants returned to the follow-up clinic. In intention-to-treat analysis for gait speed, there was a non-significant improvement favouring the intervention group (ß 0.04 m/s 95% CI -0.01, 0.08). There were no significant findings for secondary outcomes. Adherence was excellent (84.5%), usability of the app high (76.7% SD 15.3) and no serious adverse events were reported. Feedback on the app was positive and included suggestions for future updates. CONCLUSION: Due to COVID-19 the trial was under powered to detect significant results. Despite this, there was a trend towards improvement in the primary outcome measure. The excellent adherence and positive feedback about the app suggest a fully powered trial is warranted.

The Associations Between Grey Matter Volume Covariance Patterns and Gait Variability-The Tasmanian Study of Cognition and Gait.

Greater gait variability predicts dementia. However, little is known about the neural correlates of gait variability. The aims of this study were to determine (1) grey matter volume covariance patterns associated with gait variability and (2) whether these patterns were associated with specific cognitive domains. Participants (n = 351; mean age 71.9 ± 7.1) were randomly selected from the Southern Tasmanian electoral roll. Step time, step length, step width and double support time were measured using an electronic walkway. Gait variability was calculated as the standard deviation of all steps for each gait measure. Voxel-based morphometry and multivariate covariance-based analyses were used to identify grey matter patterns associated with each gait variability measure. The individual expressions of grey matter patterns were correlated with processing speed, memory, executive and visuospatial functions. The grey matter covariance pattern of double support time variability included frontal, medial temporal, anterior cingulate, insula, cerebellar and striatal regions. Greater expression of this pattern was correlated with poorer performance in all cognitive functions (p < 0.001). The covariance pattern of step length variability included frontal, temporal, insula, occipital and cerebellar regions and was correlated with all cognitive functions (p < 0.05), except memory (p = 0.76). The covariance pattern of step width variability was limited to the cerebellum and correlated only with memory (p = 0.047). No significant pattern was identified for step time variability. In conclusion, different grey matter covariance patterns were associated with individual gait variability measures. These patterns were also correlated with specific cognitive functions, suggesting common neural networks may underlie both gait and cognition.

The associations between dual-task walking under three different interference conditions and cognitive function.

BACKGROUND & AIMS: Dual-task walking is an emerging marker of cognitive impairment. However, there is uncertainty regarding which dual-task test and measure to use. The aims of this study were to determine the association between three different dual-tasks and 1) global cognition and 2) individual cognitive domains. METHODS: Participants (n = 91) were adults aged between 56-83 years (mean 68.8, SD 6.7). Under single- and dual-task, gait speed was obtained using a computerized mat. For the dual-task there were three conditions: 1) reciting alternate letters of the alphabet (DT-alpha); 2) counting backwards in 3 s (DT-counting); and 3) recalling words from a shopping list (DT-recall). Dual-task interference in gait and cognition were calculated as: (dual task-single task)/single task×100 and summed to obtain total interference. The cognitive domains of executive function, processing speed, working memory, verbal fluency, visuospatial function and verbal memory (recall and recognition) were assessed using a battery of neuropsychological tests. Raw test scores were subjected to principal component analysis to derive a global cognition score. Partial correlations were used to determine the strength of associations between single- and dual-task measures and cognitive scores, adjusting for age, sex and education. RESULTS: The strongest significant associations for each cognitive outcome variable were between greater total interference under DT-alpha and lower global cognition (r = 0.25), working memory (r = 0.28) and verbal memory [recognition] (r = 0.21), greater gait interference under DT-alpha and slower processing speed (r = 0.43) and single-task gait speed and verbal fluency (r = 0.23). Associations between dual-task measures and cognition were generally weaker under the DT-counting and DT-recall. SIGNIFICANCE: Calculating total and gait interference during DT-alpha may be the most useful in order to identify adults with poorer cognition.

Regional Associations of Cortical Thickness With Gait Variability-The Tasmanian Study of Cognition and Gait.

BACKGROUND: Gait variability is a marker of cognitive decline. However, there is limited understanding of the cortical regions associated with gait variability. We examined associations between regional cortical thickness and gait variability in a population-based sample of older people without dementia. METHOD: Participants (n = 350, mean age 71.9 ± 7.1) were randomly selected from the electoral roll. Variability in step time, step length, step width, and double support time (DST) were calculated as the standard deviation of each measure, obtained from the GAITRite walkway. Magnetic resonance imaging (MRI) scans were processed through FreeSurfer to obtain cortical thickness of 68 regions. Bayesian regression was used to determine regional associations of mean cortical thickness and thickness ratio (regional thickness/overall mean thickness) with gait variability. RESULTS: Smaller global cortical thickness was only associated with greater step width and step time variability. Smaller mean thickness in widespread regions important for sensory, cognitive, and motor functions were associated with greater step width and step time variability. In contrast, smaller thickness in a few frontal and temporal regions were associated with DST variability and the right cuneus was associated with step length variability. Smaller thickness ratio in frontal and temporal regions important for motor planning, execution, and sensory function and greater thickness ratio in the anterior cingulate was associated with greater variability in all measures. CONCLUSIONS: Examining individual cortical regions is important in understanding the relationship between gray matter and gait variability. Cortical thickness ratio highlights that smaller regional thickness relative to global thickness may be important for the consistency of gait.

Gait Characteristics and Cognitive Decline: A Longitudinal Population-Based Study.

BACKGROUND: Gait impairments are emerging predictors of dementia. However, few studies have examined whether gait predicts decline in specific cognitive domains. OBJECTIVE: This study aimed to determine whether gait speed or other gait characteristics were associated with decline in specific cognitive domains and the role of the ApoE4 genotype in modifying these associations. METHODS: Participants (n = 410; mean age 72.0±7.0 years) were randomly selected from the electoral roll. At baseline, gait speed was assessed using the GAITRite walkway. Gait variability in step time, step length, step width, and double support time (DST) was calculated as the standard deviation of each measure across all steps. In a subsample (n = 177), speed was measured under fast pace. The difference between usual and fast pace was calculated. At baseline, 2.6 and 4.6 years processing speed, memory, executive and visuospatial function were measured using neuropsychological tests. Multivariable mixed models were used to examine 1) associations between gait and the different cognitive domains over time and 2) whether the presence of ApoE4 genotype modified these associations. RESULTS: Higher DST variability was associated with greater decline in memory (p for interaction 0.03). Slow gait speed predicted decline in processing speed (p = 0.02) and visuospatial function (p = 0.03). In ApoE4 carriers, gait speed also predicted decline in memory (p = 0.02). Other gait characteristics did not predict decline in any of the cognitive domains (p > 0.05). CONCLUSIONS: These findings add to the evidence that gait is an early indicator of cognitive decline, but that specific gait measures may provide diagnostic insights into specific cognitive domains.

Medical, Sensorimotor and Cognitive Factors Associated With Gait Variability: A Longitudinal Population-Based Study.

Background: Greater gait variability increases the risk of falls. However, little is known about changes in gait variability in older age. The aims of this study were to examine: (1) change in gait variability across time and (2) factors that predict overall mean gait variability and its change over time. Methods: Participants (n = 410; mean age 72 years) were assessed at baseline and during follow up visits at an average of 30 and 54 months. Step time, step length, step width and double support time (DST) were measured using a GAITRite walkway. Variability was calculated as the standard deviation of all steps for each individual. Covariates included demographic, medical, sensorimotor and cognitive factors. Mixed models were used to determine (1) change in gait variability over time (2) factors that predicted or modified any change. Results: Over 4.6 years the presence of cardiovascular disease at baseline increased the rate of change for step length variability (p = 0.04 for interaction), lower education increased the rate of change for DST variability (p = 0.04) and weaker quadriceps strength increased the rate of change for step width variability (p = 0.01). Greater postural sway predicted greater variability on average across the three phases (p < 0.05). Arthritis, a higher body mass index (BMI), slower processing speed and lower quadriceps strength predicted greater mean step time variability (p < 0.05). Arthritis and a higher BMI predicted greater mean step length variability, while slower processing speed and BMI predicted greater mean DST variability (p < 0.05). Conclusion: Over a nearly 5-year period, variability in different gait measures do not show uniform changes over time. Furthermore, each variability measure appears to be modified and predicted by different factors. These results provide information on potential targets for future trials to maintain mobility and independence in older age.