Biological Age Acceleration and Motoric Cognitive Risk Syndrome.

OBJECTIVE: Motoric cognitive risk (MCR) syndrome, a predementia syndrome characterized by slow gait and subjective cognitive concerns, is associated with multiple age-related risk factors. We hypothesized that MCR is associated with biological age acceleration. We examined the associations of biological age acceleration with MCR, and mortality risk in MCR cases. METHODS: Biological age was determined using proteomic and epigenetic clocks in participants aged 65 years and older in the LonGenity study (N = 700, females = 57.9%) and Health and Retirement Study (HRS; N = 1,043, females = 57.1%) cohorts. Age acceleration (AgeAccel) was operationally defined as the residual from regressing predicted biological age (from both clocks separately) on chronological age. Association of AgeAccel with incident MCR in the overall sample as well as with mortality risk in MCR cases was examined using Cox models and reported as hazard ratios (HRs). RESULTS: AgeAccel scores derived from a proteomic clock were associated with prevalent MCR (odds ratio adjusted for age, gender, education years, and chronic illnesses [aOR] = 1.36, 95% confidence interval [CI] = 1.09-1.71) as well as predicted incident MCR (HR = 1.19, 95% CI = 1.00-1.41) in the LonGenity cohort. In HRS, the association of AgeAccel using an epigenetic clock with prevalent MCR was confirmed (aOR = 1.47, 95% CI = 1.16-1.85). Participants with MCR and accelerated aging (positive AgeAccel score) were at the highest risk for mortality in both LonGenity (HR = 3.38, 95% CI = 2.01-5.69) and HRS (HR = 2.47, 95% CI = 1.20-5.10). INTERPRETATION: Accelerated aging predicts risk for MCR, and is associated with higher mortality in MCR patients. ANN NEUROL 2023;93:1187-1197.

White Matter Hyperintensities Are Associated with Slower Gait Speed in Older Adults Without Dementia.

BACKGROUND: Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between cerebral small vessel disease (CSVD) imaging markers and gait speed during simple (normal pace walking (NPW)) and complex (walking-while talking (WWT)) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia. METHODS: A total of 113 Ashkenazi Jewish adults over 65 (M age=78.6±6.3 years, 45.8% women) and without dementia were examined. Established rating systems were used to quantify white matter hyperintensities (WMH) and lacunes of presumed vascular origin from Fluid Attenuated Inversion Recovery (FLAIR) images. Linear regression models adjusted for age, sex, global health, and total intracranial volume were used to examine associations between CSVD markers and gait speed during NPW and WWT. Student t-tests were used to contrast gait speed in those with "confluent-diffuse" WMH and those with "mild or no" WMH. RESULTS: The number of WMH in the basal ganglia (ß=-3.274 cm/s p=.047) and temporal lobes (ß=-3.113 cm/s p=.048) were associated with slower NPW speed in adjusted models. Participants with higher CSVD burden (confluent-diffuse pattern) in the frontal lobe (94.65 cm/s vs. 105.21 cm/s, p=.018) and globally (98.98 cm/s vs. 107.24 cm/s, p=.028) also had lower NPW speed. WMH were not associated with WWT speeds. Lacunes were not associated with NPW or WWT speed. CONCLUSION: Adjusted models found higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes were associated with slower normal pace gait speed in older adults, but not with complex walking speeds. Participants with confluent-diffuse WMHs in the frontal lobes were found to have slower average normal gait speed. Further studies are needed to establish the temporality of WMH and gait speed decline as well as mechanistic links between the two. .

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.

Everyday function profiles in prodromal stages of MCI: Prospective cohort study.

INTRODUCTION: The nature and course of limitations in everyday function in the early clinical stages of cognitive decline is not well known. METHODS: We compared complex everyday functional profiles at baseline in 59 community-dwelling older individuals with normal cognitive performance who went on to develop incident mild cognitive impairment (MCI) ("pre-MCI") with 284 older individuals who remained cognitively normal over follow-up. RESULTS: The mean number of limitations on complex everyday function at baseline was 3.1 ± 3.0 in the 59 pre-MCI cases and 2.0 ± 2.4 in the 284 normal controls (P = .003). Pre-MCI cases had limitations in traveling, entertaining, remembering appointments, and hobbies compared to normal controls. A progressive increase in mild limitations on complex everyday function preceded the incidence of MCI (mean change: pre-MCI 1.9 ± 3.6 vs normal controls 0.5 ± 2.7, P < .001). DISCUSSION: Prodromal stages of MCI are associated with progressive mild limitations in complex activities of daily living.

Dual cognitive and mobility impairments and future dementia - Setting a research agenda.

Dual cognitive and mobility impairments are associated with an increased risk of dementia. Recent studies examining temporal trajectories of mobility and cognitive function in aging found that dual decline is associated with higher dementia risk than memory decline or gait decline only. Although initial data show that individuals with dual decline or impairment have excessive cardiovascular and metabolic risk factors, the causes of dual decline or what underlies dual decline with a high risk of dementia remain largely unknown. In December 2021, the National Institute on Aging Intramural and Extramural Programs jointly organized a workshop on Biology Underlying Moving and Thinking to explore the hypothesis that older persons with dual decline may develop dementia through a specific pathophysiological pathway. The working group discussed assessment methods for dual decline and possible mechanisms connecting dual decline with dementia risk and pinpointed the most critical questions to be addressed from a translational perspective.

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.

Validation of a "subjective motoric cognitive risk syndrome" screening tool for motoric cognitive risk syndrome-A prospective cohort study.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a gait-based pre-dementia syndrome associated with risk of dementia. Ascertaining subjective cognitive and motoric complaints may facilitate early and remote identification of individuals with MCR as they are reported to precede and predict objective cognitive and motoric impairments in aging. METHODS: The validity of five subjective motoric complaint (SMC) questions and 10 subjective cognitive complaint (SCC) questions was examined for discriminating MCR in 538 non-demented community-dwelling adults. Backward logistic regression was used to identify questions to develop a weighted score to define subjective MCR (MCR-S). Receiver operating characteristic analysis was applied to determine the discriminative ability of MCR-S for the objective MCR (MCR-O) definition based on SCCs and objectively measured gait. Cox proportional hazard models adjusted for potential confounders were used to examine the predictive validity of MCR-S for incident dementia. RESULTS: Five subjective complaint questions (three SCC and two SMC) were associated with MCR-O. They were combined to define an MCR-S score (range 0-7) which yielded an area under the curve of 0.89 for discriminating MCR-O from receiver operating characteristic analysis. An optimal cut-score of 2 on the MCR-S score was determined to have good sensitivity (84%) and specificity (82%) for MCR-O. Over a median follow-up of 2.5 years, 29 participants developed dementia. Both MCR-S (adjusted hazard ratio 2.39) and MCR-O at baseline (adjusted hazard ratio 3.16) predicted risk of incident dementia. CONCLUSIONS: Subjective MCR had high concordance with MCR-O and can provide a remote screening assessment for MCR-O, which can identify those at high risk for dementia.

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.

Aging-related changes in cortical mechanisms supporting postural control during base of support and optic flow manipulations.

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to the base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults, only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7 Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12 Hz) and beta (13-30 Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.

Risk factors for the progression of motoric cognitive risk syndrome to dementia: Retrospective cohort analysis of two populations.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by cognitive complaints and slow gait. MCR is associated with increased risk of cognitive decline and incident dementia. Predictors of transition to dementia in MCR patients are still obscure. METHODS: We examined clinical, biological and lifestyle parameters related to conversion to dementia using Cox models in 439 older adults with prevalent MCR (mean age 79.87 ± 8.13 years, 70% women) from two cohorts, 268 from the Chicago-based Rush Memory and Aging project (MAP) and 171 from the Religious Orders Study (ROS), which enrolled religious clergy across the United States. RESULTS: In the pooled sample, 439 (13.2%) had prevalent MCR (268 MAP and 171 ROS). There were 140 (31.9%) incident dementia cases over a median follow up of 4.0 years. Age predicted conversion from MCR to dementia in both cohorts. Male gender was a risk factor only in ROS. In the pooled data, only higher depressive symptoms were associated with higher risk of conversion to dementia (adjusted hazard ratio [aHR] 1.13, 95% CI 1.03-1.24). Lower cognitive activity participation (aHR 0.59, 95% CI 0.44-0.79) and apolipoprotein E ε4 allele (aHR 2.57, 95% CI 1.48-4.45) predicted conversion to dementia in MAP. CONCLUSIONS: Depressive symptoms and other cohort-specific risk factors were identified as predictors of transition to dementia in individuals with MCR. These findings suggest common pathological mechanisms underlying mood, gait and cognitive declines in aging, which could help develop preventive strategies.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

Frailty, Acute Organ Dysfunction, and Increased Disability After Hospitalization in Older Adults Who Survive Critical Illness: A Prospective Cohort Study.

PURPOSE: We aimed to describe the association between prehospital frailty (PHF), acute organ dysfunction (AOD), and posthospital disability (PHD) outcome in older adults admitted to the intensive care unit (ICU). METHODS: In a prospective observational cohort study, we assessed PHF using the Clinical Frailty Scale (CFS) and assessed the level of AOD using Sequential Organ Failure Assessment (SOFA) scores on ICU day 1. We assessed Activities of Daily Living disability levels through to 6 months after discharge and used generalized estimating equations (log link and negative binomial family) to determine the independent association of PHF and AOD with PHD. RESULTS: Of the 302 patients enrolled, 221 (73.1%) survived the hospitalization. Prehospital frailty was associated with PHD (adjusted incident rate ratio [aIRR] 95% confidence interval [95% CI] per unit increase in CFS 1.38 [1.15-1.67], P = .001). Total day 1 SOFA score was weakly associated with PHD, (aIRR [95% CI] 1.05 [1.00-1.10], P = .037) while day 1 SOFA neurologic score was strongly associated with PHD (aIRR [95% CI] 1.42 [1.24-1.62] per unit increase in SOFA neurologic score, P < .001), and these effects were independent of PHF and other premorbid factors. CONCLUSIONS: Both PHF and early acute brain dysfunction are important factors associated with increasing PHD in older adults who survive critical illness.

Gray matter volume covariance networks associated with dual-task cost during walking-while-talking.

We studied gray matter volume covariance networks associated with normal pace walking (NPW) speed and dual-task costs (DTCs) during walking-while-talking (WWT)-a mobility stress test that involves walking while reciting alternate letters of the alphabet. Using a multivariate covariance-based analytic approach, we identified gray matter networks associated with NPW speed (mean 102.1 cm/s ±22.5 cm/s) and DTC (percent difference in gait speed between NPW and WWT, mean 25.9% ± 18.8%) in 139 older adults without dementia (M = 75.3 ± 6.1 years). The gray matter network associated with NPW was primarily composed of supplementary motor area, precuneus cortex, and the middle frontal gyrus. Greater expression of this NPW network was associated with better processing speed (trail-making test A [r = -0.30, p = 0.005]) and executive function (trail-making test B - A [r = -0.43, p < 0.0001]). The gray matter network associated with DTC was primarily composed of medial prefrontal, cingulate, and thalamic regions. Greater expression of this DTC network was associated with better episodic memory performance on the free and cued selective reminding test (r = 0.30, p = 0.007). These results suggest that NPW speed and DTC are supported by different networks, and are associated with different cognitive domains.

Apolipoprotein E Polymorphism and Oxidative Stress in Peripheral Blood-Derived Macrophage-Mediated Amyloid-Beta Phagocytosis in Alzheimer's Disease Patients.

Peripheral blood-derived macrophages isolated from Alzheimer's disease (AD) patients have earlier been reported to demonstrate ineffective phagocytosis of amyloid-beta compared to the age-matched control subjects. However, the mechanisms causing unsuccessful phagocytosis remain unclear. Oxidative stress and the presence of ApoEε4 allele has been reported to play a major role in the pathogenesis of AD, but the contribution of oxidative stress and ApoEε4 in macrophage dysfunction leading to ineffective Aß phagocytosis needs to be analyzed. Aß phagocytosis assay has been performed using FITC-labeled Aß and analyzed using flow cytometry and confocal imaging in patient samples and in THP-1 cells. Oxidative stress in patient-derived macrophages was analyzed by assessing the DNA damage using comet assay. ApoE polymorphism was analyzed using sequence-specific PCR and Hixson & Vernier Restriction isotyping protocol. In this study, we have analyzed the patterns of phagocytic inefficiency of macrophages in Indian population with a gradual decline in the phagocytic potential from mild cognitive impairment (MCI) to AD patients. Further, we have shown that the presence of ApoEε4 allele might also have a possible effect on the phagocytosis efficiency of the macrophages. Here, we demonstrate for the first time that oxidative stress could affect the amyloid-beta phagocytic potential of macrophages and hence by alleviating oxidative stress using curcumin, an anti-oxidant could enhance the amyloid-beta phagocytic efficacy of macrophages of patients with AD and MCI, although the responsiveness to curcumin might depends on the presence or absence of APOEε4 allele. Oxidative stress contributes significantly to decreased phagocytosis of Aß by macrophages. Moreover, the phagocytic inefficiency of macrophages was correlated to the presence of ApoEε4 allele. This study also found that the Aß-phagocytic potential of macrophage gets significantly enhanced in curcumin-treated patient-derived macrophages.

The effect of polypharmacy on prefrontal cortex activation during single and dual task walking in community dwelling older adults.

INTRODUCTION: Polypharmacy, defined as the use of 5 or more medications is associated with multiple adverse outcomes in older adults, including falls and slow gait velocity. However, the relationship between polypharmacy and cortical control of locomotion has not been reported. The purpose of this study was to examine the relationship between polypharmacy and activation patterns in the prefrontal cortex (PFC), a brain region involved in higher order control of locomotion during attention-demanding conditions. METHODS: Using Functional Near Infrared Spectroscopy (fNIRS) to quantify PFC oxygenated hemoglobin (HbO2) levels, we performed a cross sectional analysis of 325 community dwelling adults age ≥65 years, and examined HbO2 levels during single tasks (Single-Task-Walk (STW), (talking, cognitive interference (Alpha)) and Dual-Task Walk (DTW)). RESULTS: The prevalence of polypharmacy was 33% (n = 104) amongst the 325 participants (mean age 76.4 ± 6.7 years, 56% women). Among the 221 participants with no polypharmacy there was an increase in HbO2 levels from STW to DTW (estimate = -0.625; p = <0.001) and from Alpha to DTW (estimate=-0.079; p = 0.031). Polypharmacy status, however, moderated the change in HbO2 levels comparing the two single tasks to the dual-task walking condition. Specifically, the presence of polypharmacy was associated with an attenuated increase in HbO2 levels from STW to DTW (estimate = 0.149; p = 0.027) and with a decline in HbO2 levels from Alpha to DTW (estimate = 0.169; p = 0.009) after adjustments for potential confounders including medical comorbidities and the use of high-risk medications. CONCLUSION: The results of this study further support the need for clinicians to reduce polypharmacy in older adults, given its significant association with the PFC hemodynamic response during attention-demanding locomotion.

Use of an expert panel to identify domains and indicators of delirium severity.

PURPOSE: Our purpose was to create a content domain framework for delirium severity to inform item development for a new instrument to measure delirium severity. METHODS: We used an established, multi-stage instrument development process during which expert panelists discussed best approaches to measure delirium severity and identified related content domains. We conducted this work as part of the Better ASsessment of ILlness (BASIL) study, a prospective, observational study aimed at developing and testing measures of delirium severity. Our interdisciplinary expert panel consisted of twelve national delirium experts and four expert members of the core research group. Over a one-month period, experts participated in two rounds of review. RESULTS: Experts recommended that the construct of delirium severity should reflect both the phenomena and the impact of delirium to create an accurate, patient-centered instrument useful to interdisciplinary clinicians and family caregivers. Final content domains were Cognitive, Level of consciousness, Inattention, Psychiatric-Behavioral, Emotional dysregulation, Psychomotor features, and Functional. Themes debated by experts included reconciling clinical geriatrics and psychiatric content, mapping symptoms to one specific domain, and accurate capture of unclear clinical presentations. CONCLUSIONS: We believe this work represents the first application of instrument development science to delirium. The identified content domains are inclusive of various, wide-ranging domains of delirium severity and are reflective of a consistent framework that relates delirium severity to potential clinical outcomes. Our content domain framework provides a foundation for development of delirium severity instruments that can help improve care and quality of life for patients with delirium.

Motoric cognitive risk syndrome and predictors of transition to dementia: A multicenter study.

INTRODUCTION: To report clinical predictors of transition to dementia in motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait. METHODS: We examined if cognitive or motoric impairments predicted transition to dementia in 610 older adults with MCR from three cohorts. Association of cognitive (logical memory, clinical dementia rating, cognitive complaint severity, and Mini-Mental State Examination) and motoric factors (gait velocity) with dementia risk was computed using Cox models. RESULTS: There were 156 incident dementias (134 Alzheimer's disease). In the pooled sample, logical memory (adjusted hazard ratio [aHR] 0.91), cognitive complaint severity (aHR 1.53), and Mini-Mental State Examination (aHR 0.75) predicted transition of MCR to dementia. Clinical dementia rating score ≥0.5 predicted dementia (aHR 3.18) in one cohort. Gait velocity did not predict dementia. DISCUSSION: While MCR is a motoric-based predementia syndrome, severity of cognitive but not motoric impairments predicts conversion to dementia.

Walking While Talking and Risk of Incident Dementia.

INTRODUCTION: Walking while talking (WWT) is a performance-based test of divided attention that examines cognitive-motor interactions. The purpose of this study is to examine the predictive validity of WWT for dementia and dementia subtypes. METHODS: We prospectively studied the associations of WWT performance at baseline with risk of developing incident dementia in 1,156 older adults (mean age: 78.28 ± 5.27 years, 60.7% female) enrolled in the Einstein Aging Study using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: Over a median follow-up of 1.90 years (interquartile range: 4.70 years), 85 participants developed incident dementia (53 Alzheimer dementia [AD] and 26 vascular dementia [VaD]). Three gait domains were derived using principal component analysis. Only variability, which loaded heavily for swing time standard deviation (SD) and step time SD, was associated with an increased risk of incident dementia per 1 point increase (HR: 1.24, 95% CI: 1.02-1.54) and VaD (HR: 1.50, 95% CI: 1.06-2.12) after adjusting for demographics, disease burden, mental status, and normal walking velocity. Among eight individual gait variables, only swing time variability SD was associated with increased risk for both incident dementia (HR: 1.35, 95% CI: 1.03-1.77) and VaD (HR: 1.78, 95% CI: 1.12-2.83). Variability and swing time SD were not significantly associated with risk of incident AD. CONCLUSIONS: Complex walking as assessed by the WWT task is a simple and pragmatic tool for assessing risk of developing dementia, especially VaD, in older adults.

Stress and gender effects on prefrontal cortex oxygenation levels assessed during single and dual-task walking conditions.

The ability to walk is critical for functional independence and wellbeing. The pre-frontal cortex (PFC) plays a key role in cognitive control of locomotion, notably under attention-demanding conditions. Factors that influence brain responses to cognitive demands of locomotion, however, are poorly understood. Herein, we evaluated the individual and combined effects of gender and perceived stress on stride velocity and PFC Oxygenated Hemoglobin (HbO2 ) assessed during single and dual-task walking conditions. The experimental paradigm included Normal Walk (NW); Cognitive Interference (Alpha); and Walk-While-Talk (WWT) tasks. An instrumented walkway was used to assess stride velocity in NW and WWT conditions. Functional Near-Infrared-Spectroscopy (fNIRS) was used to quantify PFC HbO2 levels during NW, Alpha and WWT. Perceived task-related stress was evaluated with a single 11-point scale item. Participants were community residing older adults (age = 76.8 ± 6.7 years; %female = 56). Results revealed that higher perceived stress was associated with greater decline in stride velocity from single to dual-task conditions among men. Three-way interactions revealed that gender moderated the effect of perceived stress on changes in HbO2 levels comparing WWT to NW and Alpha. Attenuation in the increase in HbO2 levels, in high compared to low perceived stress levels, from the two single task conditions to WWT was observed only in men. Thus, older men may be more vulnerable to the effect of perceived stress on the change in PFC oxygenation levels across walking conditions that vary in terms of cognitive demands. These findings confer important implications for assessment and treatment of individuals at risk of mobility impairments.

Association Between Falls and Brain Subvolumes: Results from a Cross-Sectional Analysis in Healthy Older Adults.

Falls are a consequence of gait instability. Cortical and subcortical abnormalities have been associated with gait instability but not yet with falls. This study aims to compare the global and regional brain subvolumes between healthy older fallers and non-fallers. A total of 77 healthy older individuals (23 fallers and 54 non-fallers, 69.8 ± 3.5 years; 45.5 % female) were included in this study using a cross-sectional design. Based on an a priori hypothesis, the following brain subvolumes were quantified from three-dimensional T1-weighted MRI using FreeSurfer software: total white matter abnormalities, total white matter, total cortical and subcortical gray matter, hippocampus, motor cortex, somatosensory cortex, premotor cortex, prefrontal cortex and parietal cortex volumes. Gait performances were also recorded. Age, sex, body mass index, comorbidities, use of psychoactive drugs, far-distance visual acuity, lower-limb proprioception, depressive symptoms and cognitive scores (Mini-Mental State Examination, Frontal Assessment Battery) were used as covariates. Fallers have more frequently depressive symptoms (P = 0.048), a lower far distance visual acuity (P = 0.026) and a higher coefficient of variation of stride time (P = 0.008) compared to non-fallers. There was a trend to greater subvolumes for the somatosensory cortex (P = 0.093) and the hippocampus (P = 0.060) in the falls group. Multiple logistic regressions showed that subvolumes of the somatosensory cortex and the hippocampus (P < 0.042) were increased in fallers compared to non-fallers, even after adjustment for clinical and brain characteristics. The greater subvolumes of the somatosensory cortex and hippocampus reported in fallers compared to non-fallers suggests a possible brain compensatory mechanism involving spatial navigation and integration of sensory information.