Roee Holtzer

Quantitative gait markers and incident fall risk in older adults.

BACKGROUND Identifying quantitative gait markers of falls in older adults may improve diagnostic assessments and suggest novel intervention targets. METHODS We studied 597 adults aged 70 and older (mean age 80.5 years, 62% women) enrolled in an aging study who received quantitative gait assessments at baseline. Association of speed and six other gait markers (cadence, stride length, swing, double support, stride length variability, and swing time variability) with incident fall rate was studied using generalized estimation equation procedures adjusted for age, sex, education, falls, chronic illnesses, medications, cognition, disability as well as traditional clinical tests of gait and balance. RESULTS Over a mean follow-up period of 20 months, 226 (38%) of the 597 participants fell. Mean fall rate was 0.44 per person-year. Slower gait speed (risk ratio [RR] per 10 cm/s decrease 1.069, 95% confidence interval [CI] 1.001-1.142) was associated with higher risk of falls in the fully adjusted models. Among six other markers, worse performance on swing (RR 1.406, 95% CI 1.027-1.926), double-support phase (RR 1.165, 95% CI 1.026-1.321), swing time variability (RR 1.007, 95% CI 1.004-1.010), and stride length variability (RR 1.076, 95% CI 1.030-1.111) predicted fall risk. The associations remained significant even after accounting for cognitive impairment and disability. CONCLUSIONS Quantitative gait markers are independent predictors of falls in older adults. Gait speed and other markers, especially variability, should be further studied to improve current fall risk assessments and to develop new interventions.

Quantitative gait dysfunction and risk of cognitive decline and dementia

Background: Identifying quantitative gait markers of preclinical dementia may lead to new insights into early disease stages, improve diagnostic assessments and identify new preventive strategies. Objective: To examine the relationship of quantitative gait parameters to decline in specific cognitive domains as well as the risk of developing dementia in older adults. Methods: We conducted a prospective cohort study nested within a community based ageing study. Of the 427 subjects aged 70 years and older with quantitative gait assessments, 399 were dementia-free at baseline. Results: Over 5 years of follow-up (median 2 years), 33 subjects developed dementia. Factor analysis was used to reduce eight baseline quantitative gait parameters to three independent factors representing pace, rhythm and variability. In linear models, a 1 point increase on the rhythm factor was associated with further memory decline (by 107%), whereas the pace factor was associated with decline on executive function measured by the digit symbol substitution (by 29%) and letter fluency (by 92%) tests. In Cox models adjusted for age, sex and education, a 1 point increase on baseline rhythm (hazard ratio (HR) 1.48; 95% CI 1.03 to 2.14) and variability factor scores (HR 1.37; 95% CI 1.05 to 1.78) was associated with increased risk of dementia. The pace factor predicted the risk of developing vascular dementia (HR 1.60; 95% CI 1.06 to 2.41). Conclusion: Our findings indicate that quantitative gait measures predict future risk of cognitive decline and dementia in initially non-demented older adults.

Cognitive Processes Related to Gait Velocity: Results From the Einstein Aging Study

The authors examined the relationship between cognition and gait velocity, performed with and without interference, in elderly participants. Neuropsychological test scores from 186 cognitively normal elders were submitted to factor analysis that yielded 3 factors: Verbal IQ, Speed/Executive Attention, and Memory. Regression analyses revealed that these factors were significant predictors of variance in gait velocity, but the relationship varied as a function of task condition. All 3 factors predicted gait velocity without interference. However, the Speed/Executive Attention and Memory factors but not Verbal IQ predicted gait velocity in the interference condition. These findings suggest that gait velocity and cognitive function may have both shared and independent brain substrates. Future studies should explore gait velocity and cognitive function as predictors of dementia and falls.

The relationship between specific cognitive functions and falls in aging

The current study examined the relationship between cognitive function and falls in older people who did not meet criteria for dementia or mild cognitive impairment (N = 172). To address limitations of previous research, the authors controlled for the confounding effects of gait measures and other risk factors by means of associations between cognitive function and falls. A neuropsychological test battery was submitted to factor analysis, yielding 3 orthogonal factors (Verbal IQ, Speed/Executive Attention, Memory). Single and recurrent falls within the last 12 months were evaluated. The authors hypothesized that Speed/Executive Attention would be associated with falls. Additionally, the authors assessed whether associations between different cognitive functions and falls varied depending on whether single or recurrent falls were examined. Multivariate logistic regressions showed that lower scores on Speed/Executive Attention were associated with increased risk of single and recurrent falls. Lower scores on Verbal IQ were related only to increased risk of recurrent falls. Memory was not associated with either single or recurrent falls. These findings are relevant to risk assessment and prevention of falls and point to possible shared neural substrates of cognitive and motor function.

Gait Dysfunction in Mild Cognitive Impairment Syndromes

OBJECTIVES: To conduct a systematic clinical and quantitative assessment of gait in older adults with mild cognitive impairment (MCI) syndromes.

fNIRS Study of Walking and Walking While Talking in Young and Old Individuals

BACKGROUND Evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms. However, less is known about the functional correlates of cortical control of gait. METHODS Using functional near-infrared spectroscopy, the current study was designed to evaluate whether increased activations in the prefrontal cortex (PFC) were detected in walking while talking (WWT) compared with normal pace walking (NW) in 11 young and 11 old participants. Specifically, the following two hypotheses were evaluated: (a) Activation in the PFC would be increased in WWT compared with NW. (b) The increase in activation in the PFC during WWT as compared with NW would be greater in young than in old participants. RESULTS Separate linear mixed effects models with age as the two-level between-subject factor, walking condition (NW vs WWT) as the two-level repeated within-subject factor, and HbO2 levels in each of the 16 functional near-infrared spectroscopy channels as the dependent measure revealed significant task effects in 14 channels, indicating a robust bilateral increased activation in the PFC in WWT compared with NW. Furthermore, the group-by-task interaction was significant in 11 channels with young participants showing greater WWT-related increase in HbO2 levels compared with the old participants. CONCLUSIONS This study provided the first evidence that oxygenation levels are increased in the PFC during WWT compared with NW in young and old individuals. This effect was modified by age suggesting that older adults may under-utilize the PFC in attention-demanding locomotion tasks.

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.

Within-Person Across-Neuropsychological Test Variability and Incident Dementia

CONTEXT Neuropsychological tests are used to predict and diagnose dementia. However, to our knowledge, no studies to date have examined whether within-person across-neuropsychological test variability predicts dementia. OBJECTIVE To examine whether within-person across-neuropsychological test variability predicts future dementia. DESIGN The Einstein Aging Study (EAS) is a population-based longitudinal study of aging and dementia located in Bronx County, New York. We used Cox proportional hazards models using age as the time scale to estimate hazard ratios (HRs) for performance on individual neuropsychological tests (Free and Cued Selective Reminding Test, Digit Symbol Substitution subtest of the Wechsler Adult Intelligence Scale Revised, and the Vocabulary subtest of the Wechsler Adult Intelligence Scale Revised) and for within-person across-neuropsychological test variability as predictors of incident dementia. Analyses were stratified by sex, and controlled for education and medical illness. SETTING AND PARTICIPANTS A total of 1797 participants (age > or = 70 years) enrolled in the EAS between October 1993 and December 2007. Participants seen for the baseline visit only (n = 750), prevalent dementia cases (n = 72), and those with missing follow-up information (n = 78) were excluded. A total of 897 individuals were included in this investigation. Participants had follow-up visits every 12 to 18 months. MAIN OUTCOME MEASURE Incident dementia. RESULTS Sixty-one cases of incident dementia were identified during follow-up (mean [SD], 3.3 [2.4] years), of which 26 were in the highest quartile of within-person across-neuropsychological test variability. Adjusting for sex, education, and medical illness, variability was associated with incident dementia (HR for 1-point difference in variability, 3.93 [95% confidence interval {CI}, 2.04-7.56]). The association persisted even after adjusting for level of performance on individual neuropsychological tests (HR for 1-point difference in variability, 2.10 [95% CI, 1.04-4.23]). Comparing Cox models using neuropsychological tests with and without within-person across-neuropsychological test variability showed that the former improved the prediction of dementia. Sensitivity in a model predicting dementia at 1 year also improved when neuropsychological test variability was included. CONCLUSIONS In this population, within-person across-neuropsychological test variability was associated with development of incident dementia independent of neuropsychological test performance. This finding needs to be confirmed in future studies.

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimers disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age‐related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age‐related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.

Neuroimaging of Mobility in Aging: A Targeted Review

BACKGROUND The relationship between mobility and cognition in aging is well established, but the relationship between mobility and the structure and function of the aging brain is relatively unknown. This, in part, is attributed to the technological limitations of most neuroimaging procedures, which require the individual to be immobile or in a supine position. Herein, we provide a targeted review of neuroimaging studies of mobility in aging to promote (i) a better understanding of this relationship, (ii) future research in this area, and (iii) development of applications for improving mobility. METHODS A systematic search of peer-reviewed studies was performed using PubMed. Search terms included (i) aging, older adults, or elderly; (ii) gait, walking, balance, or mobility; and (iii) magnetic resonance imaging, voxel-based morphometry, fluid-attenuated inversion recovery, diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroencephalography, event-related potential, and functional near-infrared spectroscopy. RESULTS Poor mobility outcomes were reliably associated with reduced gray and white matter volume. Fewer studies examined the relationship between changes in task-related brain activation and mobility performance. Extant findings, however, showed that activation patterns in the cerebellum, basal ganglia, parietal and frontal cortices were related to mobility. Increased involvement of the prefrontal cortex was evident in both imagined walking conditions and conditions where the cognitive demands of locomotion were increased. CONCLUSIONS Cortical control of gait in aging is bilateral, widespread, and dependent on the integrity of both gray and white matter.