Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait ...test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI.
To determine whether a dual-task gait test is associated with incident dementia in MCI.
The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016.
Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: (single-task gait velocity - dual-task gait velocity/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition.
Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio HR, 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized.
Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI.
clinicaltrials.gov: NCT03020381.
Introduction
Gait impairment is common in neurodegenerative disorders. Specifically, gait variability—the stride‐to‐stride fluctuations in distance and time—has been associated with neurodegeneration ...and cognitive impairment. However, quantitative comparisons of gait impairments across the cognitive spectrum of dementias have not been systematically investigated.
Methods
Older adults (N = 500) with subjective cognitive impairment, Parkinson disease (PD), mild cognitive impairment (MCI), PD‐MCI, Alzheimer's disease (AD), PD‐dementia, Lewy body dementia, and frontotemporal dementia, as well cognitive normal controls, who were assessed for their gait and cognitive performance.
Results
Factor analyses grouped 11 quantitative gait parameters and identified four independent gait domains: rhythm, pace, variability, and postural control, for group comparisons and classification analysis. Among these domains, only high gait variability was associated with lower cognitive performance and accurately discriminated AD from other neurodegenerative and cognitive conditions.
Discussion
Our findings indicate that high gait variability is a marker of cognitive‐cortical dysfunction, which can help to identify Alzheimer's disease dementia.
A new paradigm is emerging in which mobility and cognitive impairments, previously studied, diagnosed, and managed separately in older adults, are in fact regulated by shared brain resources. ...Deterioration in these shared brain mechanisms by normal aging and neurodegeneration increases the risk of developing dementia, falls, and fractures. This new paradigm requires an integrated approach to measuring both domains. We aim to identify a complementary battery of existing tests of mobility and cognition in community-dwelling older adults that enable assessment of motor-cognitive interactions.
Experts on mobility and cognition in aging participated in a semistructured consensus based on the Delphi process. After performing a scoping review to select candidate tests, multiple rounds of consultations provided structured feedback on tests that captured shared characteristics of mobility and cognition. These tests needed to be sensitive to changes in both mobility and cognition, applicable across research studies and clinics, sensitive to interventions, feasible to perform in older adults, been previously validated, and have minimal ceiling/floor effects.
From 17 tests appraised, 10 tests fulfilled prespecified criteria and were selected as part of the "Core-battery" of tests. The expert panel also recommended a "Minimum-battery" of tests that included gait speed, dual-task gait speed, the Montreal Cognitive Assessment and Trail Making Test A&B.
A standardized assessment battery that captures shared characteristics of mobility and cognition seen in aging and neurodegeneration may increase comparability across research studies, detection of subtle or common reversible factors, and accelerate research progress in dementia, falls, and aging-related disabilities.
•We assessed the relationships between MRI measurements and clinical symptoms in PD.•Using longitudinal data (3 year follow-up) from 50 PD patients and 45 controls.•SN atrophy and WMHs were ...associated with additional motor deficits in PD patients.•WMHs and hippocampal atrophy were associated with cognitive deficit in PD patients.•Both grey and white matter damage contribute to motor and cognitive deficits in PD.
Previous studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinson’s disease (PD). Here we investigate these relationships in a sample of PD patients and age-matched healthy controls.
Data included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer’s disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition.
Substantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p < 0.05). Hippocampal SNIPE scores were associated with cognitve decline in both PD and controls (p < 0.01). WMH burden was significantly associated with cognitive decline and increased motor deficits in the PD group, and gait deficits in both PD and controls (p < 0.03).
While substantia nigra atrophy and WMH burden were significantly associated with additional motor deficits, WMH burden and hippocampal atrophy were associated with cognitive deficits in PD patients. These results suggest an additive contribution of both grey and white matter damage to the motor and cognitive deficits in PD.
Cerebral microbleeds (CMBs) are very frequent diagnoses with MRI imaging in the elderly or in patients with cerebral infarction, intracranial hemorrhage (ICH), and dementia. The mechanisms for CMBs ...are not fully understood but may be secondary to injury to the vascular wall from long-standing hypertension or amyloid deposition in the tissue. The presence of CMB increases the risk for stroke, dementia, and death. The increasing number of CMBs is also associated with a higher risk of hemorrhagic complications with the long-term use of anticoagulants in atrial fibrillation and in patients requiring thrombolysis for acute stroke. The presence of CMBs is however not a contraindication for anticoagulation or thrombolysis as was recently shown from the results of the CROMIS-2 study. This review will summarize our current understanding of the natural history of CMBs and offer suggestions on the best management in common clinical settings.
Mild behavioral impairment (MBI) and dual-task gait cost (DTGC) are two non-cognitive markers of dementia that capture behavioral and motor symptoms. We investigated the relationship between MBI and ...DTGC in a sample of non-demented older adults.
This was a cross-sectional observational study of 193 participants (10 cognitively normal, 48 subjective cognitive decline (SCD), 135 mild cognitive impairment (MCI); 52.8% female) from 13 Canadian sites from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to define MBI severity using a published algorithm. DTGC, the percentage difference between dual-task and preferred walking speeds, was assessed under three cognitive tasks: animal naming, counting backwards, and serial seven subtractions. Associations were tested in the entire cohort and in the MCI subgroup using multivariable linear regression adjusted for age, sex, education, and diagnosis. The role of global cognition, executive function, verbal and working memory in the association were investigated using tests of mediation and moderation.
MBI symptoms were present in 46.6% of participants (mean age = 72.4 years). Greater overall MBI burden was associated with lower gait speed across all conditions. Furthermore, a one-point increase in global MBI symptom severity was associated with a 0.8% increase in DTGC in the animal fluency condition, a 0.9% increase in the counting backwards condition and a 1.1% increase in the serial sevens condition. These associations were strongest in the subgroup of MCI participants. Executive function but not global cognition or verbal and working memory mediated the association between MBI and DTGC in all three conditions.
MBI is associated with gait speed and DTGC in this group of non-demented individuals, independent of the presence or absence of MCI. These findings provide evidence of the relationship between these non-cognitive dementia markers of behavior and gait beyond cognitive impairment.
•MBI and DTGC are non-cognitive risk markers of dementia.•MBI and DTGC are associated with each other in a non-dementia cohort.•MBI and DTGC may enhance the detection of older adults at risk of dementia.
Reduced cerebrovascular reactivity is proposed to be a feature of cerebral amyloid angiopathy (CAA) but has not been measured directly. Employing a global vasodilatory stimulus (hypercapnia), this ...study assessed the relationships between cerebrovascular reactivity and MRI markers of CAA and cognitive function.
In a cross-sectional study, individuals with probable CAA, mild cognitive impairment, or dementia due to Alzheimer disease and healthy controls underwent neuropsychological testing and an MRI that included a 5% carbon dioxide challenge. Cerebrovascular reactivity was compared across groups controlling for age, sex, and the presence of hypertension, and its associations with MRI markers of CAA in participants with CAA and with cognition across all participants were determined using multivariable linear regression adjusting for group, age, sex, education, and the presence of hypertension.
Cerebrovascular reactivity data (mean ± SD) were available for 26 participants with CAA (9 female; 74.4 ± 7.7 years), 19 participants with mild cognitive impairment (5 female; 72.1 ± 8.5 years), 12 participants with dementia due to Alzheimer disease (4 female; 69.4 ± 6.6 years), and 39 healthy controls (30 female; 68.8 ± 5.4 years). Gray and whiter matter reactivity averaged across the entire brain was lower in participants with CAA and Alzheimer disease dementia compared to healthy controls, with a predominantly posterior distribution of lower reactivity in both groups. Higher white matter hyperintensity volume was associated with lower white matter reactivity (standardized coefficient β, 95% CI -0.48, -0.90 to -0.01). Higher gray matter reactivity was associated with better global cognitive function (β 0.19, 0.03-0.36), memory (β 0.21, 0.07-0.36), executive function (β 0.20, 0.02-0.39), and processing speed (β 0.27, 0.10-0.45) and higher white matter reactivity was associated with higher memory (β 0.22, 0.08-0.36) and processing speed (β 0.23, 0.06-0.40).
Reduced cerebrovascular reactivity is a core feature of CAA and its assessment may provide an additional biomarker for disease severity and cognitive impairment.
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