Dual decline in gait speed and cognition is associated with future dementia: evidence for a phenotype.

BACKGROUND: concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of 'dual decliners', those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. METHODS: prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants' gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. RESULTS: among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23-7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. CONCLUSION: older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.

Mapping Associations Between Gait Decline and Fall Risk in Mild Cognitive Impairment.

OBJECTIVES: Compared to their cognitively healthy counterparts, older adults with mild cognitive impairment (MCI) exhibit higher risk of falls, specifically with injuries. We sought to determine whether fall risk in MCI is associated with decline in higher-level brain gait control. DESIGN: Longitudinal study. SETTING: Community-dwelling adults from the Gait and Brain Study Cohort. PARTICIPANTS: A total of 110 participants, aged 65 years or older, with MCI. MEASUREMENTS: Biannual assessments for medical characteristics, cognitive performance, fall incidence, and gait performance for up to 7 years. Seven spatiotemporal gait parameters, including variabilities, were recorded using a 6-meter electronic walkway. Principal components analysis was used to identify independent gait domains related to higher-level (pace and variability domains) and lower-level (rhythm domain) brain control. Associations between gait decline and incident falls were studied with Cox regression models adjusted for baseline covariates. RESULTS: Of participants enrolled, 40% experienced at least one fall (28% of them with injuries) over a mean follow-up of 31.6 ± 23.9 months. From the pace domain, slower gait speed (adjusted hazard ratio [aHR] per 10-cm/s decrease = 4.62; 95% confidence interval [CI] = 1.84-11.61; P = .001) was associated with severe injurious falls requiring emergency room (ER) visit; from the variability domain, stride time variability (aHR per 10% increase during follow-up = 2.17; 95% CI = 1.02-4.63; P = .04) was associated with higher risk of all injurious falls. Rhythm domain was not associated with fall risk. Decline in pace domain was significantly associated with falls with ER visit (aHR = 3.67; 95% CI = 1.46-9.19; P = .005). After adjustments for multiple comparisons, gait speed and pace domain remained significantly associated with falls with ER visits. No statistically significant associations were found between gait domains and overall falls (P ≥ .06). CONCLUSION: Higher risk of injurious falls in older adults with MCI is associated with decline in gait parameters related to higher-level brain control. J Am Geriatr Soc 68:576-584, 2020.

Do depressive symptoms affect balance in older adults with mild cognitive impairment? Results from the "gait and brain study".

BACKGROUND: Mild cognitive impairment (MCI) and depression independently affect balance control in older adults. However, it is uncertain whether depressive symptoms would amplify balance problems in older adults with MCI. AIM: To evaluate if the presence of significant depressive symptoms affects postural sway under somatosensory challenges in a MCI population. METHODS: Eighty two participants (mean of 75.3 ±â€¯6.4 years of age; 46% women) with MCI completed cognitive and balance assessments. Participants were grouped by severity of depressive symptoms using the Geriatric Depression Scale-15, as MCI with depressive symptoms (MCI-D = 14, score ≥ 5) and MCI without depressive symptoms (MCI = 68, score < 5). Postural sway area was evaluated during eyes open (EO) and eyes closed (EC) while standing on a rigid flat force plate platform, and compared across groups. Analyses were controlled for age, sex, comorbidities, anti-depressant medication use, executive function, and baseline sway. RESULTS: MCI-D showed larger postural sway area when compared with MCI irrespective of visual feedback conditions (p = 0.03). This difference remained significant after adjusting for anti-depressant use and executive function performance. The lack of interaction between groups and visual condition was associated with group differences in postural sway during EO condition (Beta = 0.08, CI -257.5-621.9; p = 0.41) and by comparable sway increase from EO to EC in both groups. CONCLUSION: Depressive symptoms in individuals with MCI worsened postural stability during both eyes open and eyes closed conditions independently of cognitive function. Significant depressive symptoms may affect balance in MCI populations, potentially increasing the risk of falls.

The effects of physical exercise on executive function in community-dwelling older adults living with Alzheimer's-type dementia: A systematic review.

Executive function deficit is an indicator of Alzheimer's-type dementia and manifests as disruptions of attentional control, memory, cognitive flexibility, planning, and reasoning, among other cognitive problems. Physical exercise is suggested to have a protective effect on global cognition with aging. However, whether it influences executive function in people living with Alzheimer's-type dementia specifically is unknown. The current systematic review examined the efficacy of physical exercise on executive function performance in community-dwelling older adults living with Alzheimer's-type dementia. An electronic search of databases retrieved randomized and non-randomized controlled trials of community-dwelling older adults diagnosed with Alzheimer's-type dementia who completed a physical exercise intervention and who were assessed using an executive function outcome measure. Methodological quality of six studies meeting the inclusion criteria published between 2009 and 2016 was scored independently by two raters using the Physiotherapy Evidence Database and a Cochrane informed domain-based assessment of risk of bias. Trends toward improvement in executive function scores were seen across all six studies, and significant improvement was seen in four of the eligible studies. Future studies should explore the benefits of the American College of Sports Medicine recommended 150 min of physical exercise per week with select measures of executive function.

Motor and Cognitive Trajectories Before Dementia: Results from Gait and Brain Study.

OBJECTIVES: To compare the trajectories of motor and cognitive decline in older adults who progress to dementia with the trajectories of those who do not. To evaluate the added value of measuring motor and cognitive decline longitudinally versus cross-sectionally for predicting dementia. DESIGN: Prospective cohort study with 5 years of follow-up. SETTING: Clinic based at a university hospital in London, Ontario, Canada. PARTICIPANTS: Community-dwelling participants aged 65 and older free of dementia at baseline (N=154). MEASUREMENTS: We evaluated trajectories in participants' motor performance using gait velocity and cognitive performance using the MoCA test twice a year for 5 years. We ascertained incident dementia risk using Cox regression models and attributable risk analyses. Analyses were adjusted using a time-dependent covariate. RESULTS: Overall, 14.3% progressed to dementia. The risk of dementia was almost 7 times as great for those whose gait velocity declined (hazard ratio (HR)=6.89, 95% confidence interval (CI)=2.18-21.75, p=.001), more than 3 times as great for those with cognitive decline (HR=3.61, 95% CI=1.28-10.13, p=.01), and almost 8 times as great in those with combined gait velocity and cognitive decline (HR=7.83, 95% CI=2.10-29.24, p=.002), with an attributable risk of 105 per 1,000 person years. Slow gait at baseline alone failed to predict dementia (HR=1.16, 95% CI=0.39-3.46, p=.79). CONCLUSION: Motor decline, assessed according to serial measures of gait velocity, had a higher attributable risk for incident dementia than did cognitive decline. A decline over time of both gait velocity and cognition had the highest attributable risk. A single time-point assessment was not sufficient to detect individuals at high risk of dementia.

Risk Factors Associated with Falls in Older Adults with Dementia: A Systematic Review.

Purpose: People with dementia fall more often than cognitively healthy older adults, but their risk factors are not well understood. A review is needed to determine a fall risk profile for this population. The objective was to critically evaluate the literature and identify the factors associated with fall risk in older adults with dementia. Methods: Articles published between January 1988 and October 2014 in EMBASE, PubMed, PsycINFO, and CINAHL were searched. Inclusion criteria were participants aged 55 years or older with dementia or cognitive impairment, prospective cohort design, detailed fall definition, falls as the primary outcome, and multi-variable regression analysis. Two authors independently reviewed and extracted data on study characteristics, quality assessment, and outcomes. Adjusted risk estimates were extracted from the articles. Results: A total of 17 studies met the inclusion criteria. Risk factors were categorized into demographic, balance, gait, vision, functional status, medications, psychosocial, severity of dementia, and other. Risk factors varied with living setting and were not consistent across all studies within a setting. Conclusion: Falls in older adults with dementia are associated with multiple intrinsic and extrinsic risk factors, some shared with older adults in general and others unique to the disease. Risk factors vary between community- and institution-dwelling samples of adults with dementia or cognitive impairment.

Objectif : les personnes atteintes de démence sont plus souvent victimes de chute que les personnes âgées en bonne santé cognitive, mais leurs facteurs de risque ne sont pas bien compris. Un examen est nécessaire pour déterminer un profil de risque de chute pour cette population. L'objectif était d'évaluer de manière critique les publications et de cibler les facteurs associés au risque de chute chez les personnes âgées atteintes de démence. Méthodologie : les articles publiés entre janvier 1988 et octobre 2014 dans les bases de données EMBRASE, PubMed, PsycINFO et CINAHL ont été analysés. Critères d'inclusion : personnes âgées de 55 ans et plus atteintes de démence ou d'un déficit cognitif, cohorte prospective, définition détaillée de la chute, la chute comme résultat primaire et analyse de régression multivariée. Deux auteurs ont examiné et extrait, de manière indépendante, les données relatives aux caractéristiques des études, à l'évaluation de la qualité et aux résultats. Les évaluations ajustées en fonction du risque ont été extraites des articles. Résultats : au total, 17 études respectaient les critères d'inclusion. Les facteurs de risque ont été regroupés dans les catégories suivantes : facteurs démographiques, équilibre, démarche, vision, état fonctionnel, médicaments, facteurs psychosociaux, gravité de la démence et autre. Les facteurs de risque variaient en fonction du cadre de vie et n'étaient pas constants parmi toutes les études au sein d'un même cadre. Conclusion : les chutes chez les personnes âgées atteintes de démence sont associées à de nombreux facteurs de risque intrinsèques et extrinsèques, certains étant communs aux personnes âgées en général et d'autres étant propres à la maladie. Les facteurs de risque varient entre les échantillons d'adultes atteints de démence ou d'un déficit cognitif vivant dans la collectivité ou dans un établissement.

Disentangling Cognitive-Frailty: Results From the Gait and Brain Study.

BACKGROUND: Cognitive-frailty, defined as the presence of both frailty and cognitive impairment, is proposed as a distinctive entity that predicts dementia. However, it remains controversial whether frailty alone, cognitive-frailty, or the combination of cognitive impairment and slow gait pose different risks of incident dementia. METHODS: Two hundred and fifty-two older adults free of dementia at baseline (mean age 76.6±8.6 years) were followed up to 5 years with bi-annual visits including medical, cognitive, and gait assessments. Incident all-cause of dementia and cognitive decline were the main outcomes. Frailty was defined using validated phenotypic criteria. Cognition was assessed using the Montreal Cognitive Assessment while gait was assessed using an electronic walkway. Cox Proportional Hazards models were used to estimate the risk of cognitive decline and dementia for frailty, cognitive-frailty, and gait and cognition models. RESULTS: Fifty-three participants experienced cognitive decline and 27 progressed to dementia (incident rate: 73/1,000 person-years). Frailty participants had a higher prevalence of cognitive impairment compared with those without frailty (77% vs. 54%, p = .02) but not significant risk to incident dementia. Cognitive-frailty increased incident rate (80/1,000 person-years) but not risk for progression to dementia. The combination of slow gait and cognitive impairment posed the highest risk for progression to dementia (hazard ratio: 35.9, 95% confidence interval: 4.0-319.2; p = 0.001, incident rate: 130/1,000 person-years). None of the models explored significantly predicted cognitive decline. CONCLUSIONS: Combining a simple motor test, such as gait velocity, with a reliable cognitive test like the Montreal Cognitive Assessment is superior than the cognitive-frailty construct to detect individuals at risk for dementia. Cognitive-frailty may embody two different manifestations, slow gait and low cognition, of a common underlying mechanism.

Reliability of the Berg Balance Scale as a Clinical Measure of Balance in Community-Dwelling Older Adults with Mild to Moderate Alzheimer Disease: A Pilot Study.

PURPOSE: To measure test-retest and interrater reliability of the Berg Balance Scale (BBS) in community-dwelling adults with mild to moderate Alzheimer disease (AD). Method : A sample of 15 adults (mean age 80.20 [SD 5.03] years) with AD performed three balance tests: the BBS, timed up-and-go test (TUG), and Functional Reach Test (FRT). Both relative reliability, using the intra-class correlation coefficient (ICC), and absolute reliability, using standard error of measurement (SEM) and minimal detectable change (MDC95) values, were calculated; Bland-Altman plots were constructed to evaluate inter-tester agreement. The test-retest interval was 1 week. Results : For the BBS, relative reliability values were 0.95 (95% CI, 0.85-0.98) for test-retest reliability and 0.72 (95% CI, 0.31-0.91) for interrater reliability; SEM was 6.01 points and MDC95 was 16.66 points; and interrater agreement was 16.62 points. The BBS performed better in test-retest reliability than the TUG and FRT, tests with established reliability in AD. Between 33% and 50% of participants required cueing beyond standardized instructions because they were unable to remember test instructions. Conclusions : The BBS achieved relative reliability values that support its clinical utility, but MDC95 and agreement values indicate the scale has performance limitations in AD. Further research to optimize balance assessment for people with AD is required.

Objectif : Mesurer la fiabilité test-retest et interévaluateurs de l'échelle de Berg chez les adultes âgés qui résident dans la collectivité et qui sont atteints de la maladie d'Alzheimer au stade léger à modéré. Méthode : Un échantillon de 15 adultes (âge moyen de 80,20 [ET de 5,03] ans) atteints d'Alzheimer ont effectué trois tests d'équilibre : l'échelle de Berg (Berg Balance Scale), le test de lever et marcher chronométré (timed up-and-go [TUG]) et le test de portée fonctionnelle (Functional Reach Test). La fiabilité relative, à l'aide du coefficient de corrélation intraclasse (CCI) et la fiabilité absolue, à l'aide de l'erreur type de mesure (ETM) et des valeurs de changement détectable minimal (CDM95), ont été calculées; des courbes de Bland et Altman ont été construites pour évaluer la convergence interévaluateurs. L'intervalle de test-retest était d'une semaine. Résultats : En ce qui concerne l'échelle de Berg, les valeurs de fiabilité relative étaient de 0,95 (95% CI, 0,85 à 0,98) pour la fiabilité test-retest et de 0,72 (95% CI, 0,31 à 0,91) pour la fiabilité interévaluateurs; l'ETM était de 6,01 points et le CDM95 était de 16,66 points, tandis que la convergence interévaluateur était de 16,62 points. L'échelle de Berg a obtenu de meilleurs résultats que les tests de lever et marcher chronométré et de portée fonctionnelle, tests ayant une fiabilité établie pour l'Alzheimer en fiabilité test-retest. De 33% à 50% des participants avaient besoin de plus de directives que les instructions normalisées, car ils n'étaient pas capables de se souvenir des instructions de test. Conclusions : L'échelle de Berg a obtenu des valeurs de fiabilité relative qui appuient son utilité clinique, mais les valeurs de CDM95 et de convergence indiquent que cette échelle présente des limites en matière de rendement pour les cas d'Alzheimer. D'autres recherches visant l'optimisation de l'évaluation de l'équilibre chez les personnes atteintes d'Alzheimer doivent être effectuées.

Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial.

BACKGROUND: Gait deficits are prevalent in people with dementia and increase their fall risk and future disability. Few treatments exist for gait impairment in Alzheimer's disease (AD) but preliminary studies have shown that cognitive enhancers may improve gait in this population. OBJECTIVE: To determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic activity, on gait in older adults newly diagnosed with AD. METHODS: Phase II clinical trial in 43 seniors with mild AD who received donepezil. Participants had not previously received treatment with cognitive enhancers. Primary outcome variables were gait velocity (GV) and stride time variability (STV) under single and dual-task conditions measured using an electronic walkway. Secondary outcomes included attention and executive function. RESULTS: After four months of treatment, participants with mild AD improved their GV from 108.4 ± 18.6 to 113.3 ± 19.5 cm/s, p = 0.010; dual-task GV from 80.6 ± 23.0 to 85.3 ± 22.3 cm/s, p = 0.028. Changes in STV were in the expected direction although not statistically significant. Participants also showed improvements in Trail Making Tests A (p = 0.030), B (p = 0.001), and B-A (p = 0.042). CONCLUSION: Donepezil improved gait in participants with mild AD. The enhancement of dual-task gait suggests the positive changes achieved in executive function as a possible causal mechanism. This study yielded a clinically significant estimate of effect size; as well, the findings are relevant to the feasibility and ethics considerations for the design of a Phase III clinical trial.

The motor signature of mild cognitive impairment: results from the gait and brain study.

BACKGROUND: Early motor changes associated with aging predict cognitive decline, which suggests that a "motor signature" can be detected in predementia states. In line with previous research, we aim to demonstrate that individuals with mild cognitive impairment (MCI) have a distinct motor signature, and specifically, that dual-task gait can be a tool to distinguish amnestic (a-MCI) from nonamnestic MCI. METHODS: Older adults with MCI and controls from the "Gait and Brain Study" were assessed with neurocognitive tests to assess cognitive performance and with an electronic gait mat to record temporal and spatial gait parameters. Mean gait velocity and stride time variability were evaluated under simple and three separate dual-task conditions. The relationship between cognitive groups (a-MCI vs nonamnestic MCI) and gait parameters was evaluated with linear regression models and adjusted for confounders. RESULTS: Ninety-nine older participants, 64 MCI (mean age 76.3±7.1 years; 50% female), and 35 controls (mean age 70.4±3.9 years; 82.9% female) were included. Forty-two participants were a-MCI and 22 were nonamnestic MCI. Multivariable linear regression (adjusted for age, sex, physical activity level, comorbidities, and executive function) showed that a-MCI was significantly associated with slower gait and higher dual-task cost under dual-task conditions. CONCLUSION: Participants with a-MCI, specifically with episodic memory impairment, had poor gait performance, particularly under dual tasking. Our findings suggest that dual-task assessment can help to differentiate MCI subtyping, revealing a motor signature in MCI.

Identifying balance and fall risk in community-dwelling older women: the effect of executive function on postural control.

PURPOSE: The mechanisms linking cognition, balance function, and fall risk among older adults are not fully understood. An evaluation of the effect of cognition on balance tests commonly used in clinical practice to assess community-dwelling older adults could enhance the identification of at-risk individuals. The study aimed to determine (1) the association between cognition and clinical tests of balance and (2) the relationship between executive function (EF) and balance under single- and dual-task testing. METHODS: Participants (24 women, mean age of 76.18 [SD 16.45] years) completed six clinical balance tests, four cognitive tests, and two measures of physical function. RESULTS: Poor balance function was associated with poor performance on cognitive testing of EF. In addition, the association with EF was strongest under the dual-task timed up-and-go (TUG) test and the Fullerton Advanced Balance Scale. Measures of global cognition were associated only with the dual-task performance of the TUG. Postural sway measured with the Standing Balance Test, under single- or dual-task test conditions, was not associated with cognition. CONCLUSIONS: Decreased EF was associated with worse performance on functional measures of balance. The relationship between EF and balance was more pronounced with dual-task testing using a complex cognitive task combined with the TUG.

Objectif   : On ne comprend pas à fond les mécanismes qui établissent un lien entre la cognition, la fonction équilibre et le risque de chute chez les adultes âgés. L'évaluation de l'effet de la cognition sur les tests d'équilibre d'usage courant en pratique clinique pour évaluer les adultes âgés vivant dans des logements communautaires pourrait aider à repérer les personnes à risque. L'étude visait à déterminer le lien entre (1) la cognition et les tests cliniques d'équilibre et (2) la fonction d'exécution (FE) et l'équilibre au cours d'un test à tâche simple et à tâche double. Méthodes : Les participantes (24 femmes, âge moyen de 76,18 [ET 16,45] ans) se sont soumises à six tests d'équilibre clinique, quatre tests de cognition et deux mesures de fonction physique. Résultats : On a établi un lien entre une mauvaise fonction d'équilibre et un rendement médiocre au test cognitif de FE. En outre, le lien avec la FE était le plus solide dans le contexte du test chronométré à double tâche lever et marcher et du test d'équilibre avancé de Fullerton. On a établi un lien entre des mesures de la cognition globale et le rendement à l'exécution du test chronométré lever et marcher à double tâche seulement. On n'a pas établi de lien entre le balancement postural mesuré au moyen du test d'équilibre debout à tâche simple ou à tâche double et la cognition. Conclusions : On a établi un lien entre une baisse de la FE et le rendement le plus mauvais des mesures fonctionnelles de l'équilibre. Le lien entre la FE et l'équilibre était plus marqué au cours des tests à double tâche utilisant une tâche cognitive complexe combinée au test chronométré lever et marcher.

Motoric cognitive risk syndrome: multicountry prevalence and dementia risk.

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings.