Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort

Muurling, Marijn; Rhodius-Meester, Hanneke F.M.; Pärkkä, Juha; Gils, Mark van; Frederiksen, Kristian Steen; Bruun, Marie; Hasselbalch, Steen G.; Herukka, Sanna Kaisa; Hallikainen, Merja; Teunissen, Charlotte E.; Visser, Pieter Jelle; Scheltens, Philip; Flier, Wiesje M. van der; Mattila, Jussi; Lötjönen, Jyrki; Boer, Casper de

doi:10.3233/jad-200225

Cited by 15 publications

(25 citation statements)

References 37 publications

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“…Pathologic tau also has been linked to gait disturbance (Muurling et al, 2020), but additional studies are needed to fully understand the connections between tauopathies and gait dysfunction . Like humans, slow gait in vervets was associated with lower CSF Aβ 1-42 and higher brain concentrations of Aβ 1-42 (Latimer et al, 2019).…”

Section: Neuropathologic Changes and Physical Declinementioning

confidence: 99%

“…In adults aged 50–69 years, slow gait was associated with PET measures of Aβ accumulation in multiple brain regions, particularly the temporal lobe (Wennberg, Savica & Hagen, Roberts, et al, 2017). Pathologic tau also has been linked to gait disturbance (Muurling et al, 2020), but additional studies are needed to fully understand the connections between tauopathies and gait dysfunction (Wennberg et al, 2017). Like humans, slow gait in vervets was associated with lower CSF Aβ 1–42 and higher brain concentrations of Aβ 1–42 (Latimer et al, 2019).…”

Section: Aging‐related Physical Declinementioning

confidence: 99%

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Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

Frye

Craft

Latimer

et al. 2021

American J Primatol

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Age-related neurodegeneration characteristic of late-onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a model of aging-related AD-like neuropathology and associated phenotypes including cognitive function, physical function, glucose handling, intestinal physiology, and CSF, blood, and neuroimaging biomarkers. This review provides the most comprehensive multisystem description of aging in vervets to date. This review synthesizes a large body of evidence that suggests that aging vervets exhibit a coordinated suite of traits consistent with early AD and provide a powerful, naturally occurring model for LOAD. Notably, relationships are identified between AD-like neuropathology and modifiable risk factors. Gaps in knowledge and key limitations are provided to shape future studies to illuminate mechanisms underlying divergent neurocognitive aging trajectories and to develop interventions that increase resilience to aging-associated chronic disease, particularly, LOAD.

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Section: Neuropathologic Changes and Physical Declinementioning

confidence: 99%

Section: Aging‐related Physical Declinementioning

confidence: 99%

Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

Frye

Craft

Latimer

et al. 2021

American J Primatol

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“…Quantitative tests have revealed gait dysfunction in subjects with amnestic and non-amnestic mild cognitive impairment (MCI) subtypes compared with healthy controls ( Verghese et al, 2008 ). Furthermore, cognitive impairment has been found to affect spatiotemporal parameters of gait under dual-task performance ( Montero-Odasso et al, 2014 ; Muurling et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Gait Kinematic and Kinetic Characteristics of Older Adults With Mild Cognitive Impairment and Subjective Cognitive Decline: A Cross-Sectional Study

Zhong

Ali

Gao

et al. 2021

Front. Aging Neurosci.

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BackgroundOlder adults with mild cognitive impairment (MCI) have slower gait speed and poor gait performance under dual-task conditions. However, gait kinematic and kinetic characteristics in older adults with MCI or subjective cognitive decline (SCD) remain unknown. This study was designed to explore the difference in gait kinematics and kinetics during level walking among older people with MCI, SCD, and normal cognition (NC).MethodsThis cross-sectional study recruited 181 participants from July to December 2019; only 82 met the inclusion criteria and consented to participate and only 79 completed gait analysis. Kinematic and kinetic data were obtained using three-dimensional motion capture system during level walking, and joint movements of the lower limbs in the sagittal plane were analyzed by Visual 3D software. Differences in gait kinematics and kinetics among the groups were analyzed using multivariate analysis of covariance (MANCOVA) with Bonferroni post-hoc analysis. After adjusting for multiple comparisons, the significance level was p < 0.002 for MANCOVA and p < 0.0008 for post-hoc analysis.ResultsTwenty-two participants were MCI [mean ± standard deviation (SD) age, 71.23 ± 6.65 years], 33 were SCD (age, 72.73 ± 5.25 years), and 24 were NC (age, 71.96 ± 5.30 years). MANCOVA adjusted for age, gender, body mass index (BMI), gait speed, years of education, diabetes mellitus, and Geriatric Depression Scale (GDS) revealed a significant multivariate effect of group in knee peak extension angle (F = 8.77, p < 0.0001) and knee heel strike angle (F = 8.07, p = 0.001) on the right side. Post-hoc comparisons with Bonferroni correction showed a significant increase of 5.91° in knee peak extension angle (p < 0.0001) and a noticeable decrease of 6.21°in knee heel strike angle (p = 0.001) in MCI compared with NC on the right side. However, no significant intergroup difference was found in gait kinetics, including dorsiflexion, plantar flexion, knee flexion, knee extension, hip flexion, and hip extension(p > 0.002).ConclusionAn increase of right knee peak extension angle and a decrease of right knee heel strike angle during level walking were found among older adults with MCI compared to those with NC.

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“… 29 Gait abnormalities are common in MCR and are associated with accelerated functional decline and gray matter atrophy in motor, insular and prefrontal cortex linked to the control aspects of gait such as motor planning and modulation. 30 Muurling et al, 31 have shown an association between gait specific measures related to pace and rhythm, cerebrospinal fluid (CSF) hyperphosphorylated tau and dementia. Muurling’s work is key for this investigation given that Metropolitan Mexico City residents show evidence of Alzheimer’s disease in 202/203 forensic autopsy cases age 25.36 ± 9.23 y, CSF Aβ1-42, BDNF, α-synuclein, and inflammatory markers are evolving in young urbanites showing underperformance in cognitive processes, and abnormal brainstem evoked potentials.…”

Section: Introductionmentioning

confidence: 99%

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young

Calderón‐Garcidueñas

Torres-Solorio

Kulesza

et al. 2020

Environmental Research

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To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM 2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg tests in 575 clinically healthy subjects, age 21.0±5.7y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3± 9.1y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM 2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM 2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM 2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.

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Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort

Cited by 15 publications

References 37 publications

Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

Gait Kinematic and Kinetic Characteristics of Older Adults With Mild Cognitive Impairment and Subjective Cognitive Decline: A Cross-Sectional Study

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young

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