Dataset Information

Cognition and motor function: The gait and cognition pooled index.

ABSTRACT: BACKGROUND:There is a need for outcome measures with improved responsiveness to changes in pre-dementia populations. Both cognitive and motor function play important roles in neurodegeneration; motor function decline is detectable at early stages of cognitive decline. This proof of principle study used a Pooled Index approach to evaluate improved responsiveness of the predominant outcome measure (ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale) when assessment of motor function is added. METHODS:Candidate Pooled Index variables were selected based on theoretical importance and pairwise correlation coefficients. Kruskal-Wallis and Mann-Whitney U tests assessed baseline discrimination. Standardized response means assessed responsiveness to longitudinal change. RESULTS:Final selected variables for the Pooled Index include gait velocity, dual-task cost of gait velocity, and an ADAS-Cog-Proxy (statistical approximation of the ADAS-Cog using similar cognitive tests). The Pooled Index and ADAS-Cog-Proxy scores had similar ability to discriminate between pre-dementia syndromes. The Pooled Index demonstrated trends of similar or greater responsiveness to longitudinal decline than ADAS-Cog-Proxy scores. CONCLUSION:Adding motor function assessments to the ADAS-Cog may improve responsiveness in pre-dementia populations.

SUBMITTER: Kueper JK

PROVIDER: S-EPMC7485843 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cognition and motor function: The gait and cognition pooled index.

Kueper Jacqueline K JK Lizotte Daniel J DJ Montero-Odasso Manuel M Speechley Mark M

PloS one 20200911 9

<h4>Background</h4>There is a need for outcome measures with improved responsiveness to changes in pre-dementia populations. Both cognitive and motor function play important roles in neurodegeneration; motor function decline is detectable at early stages of cognitive decline. This proof of principle study used a Pooled Index approach to evaluate improved responsiveness of the predominant outcome measure (ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale) when assessment of motor ...[more]

PMID: 32915845

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Project description:Neurological dysfunction following viral infection varies among individuals, largely due to differences in their genetic backgrounds. Gait patterns, which can be evaluated using measures of coordination, balance, posture, muscle function, step-to-step variability, and other factors, are also influenced by genetic background. Accordingly, to some extent gait can be characteristic of an individual, even prior to changes in neurological function. Because neuromuscular aspects of gait are under a certain degree of genetic control, the hypothesis tested was that gait parameters could be predictive of neuromuscular dysfunction following viral infection. The Collaborative Cross (CC) mouse resource was utilized to model genetically diverse populations and the DigiGait treadmill system used to provide quantitative and objective measurements of 131 gait parameters in 142 mice from 23 CC and SJL/J strains. DigiGait measurements were taken prior to infection with the neurotropic virus Theiler's Murine Encephalomyelitis Virus (TMEV). Neurological phenotypes were recorded over 90 days post-infection (d.p.i.), and the cumulative frequency of the observation of these phenotypes was statistically associated with discrete baseline DigiGait measurements. These associations represented spatial and postural aspects of gait influenced by the 90 d.p.i. phenotype score. Furthermore, associations were found between these gait parameters with sex and outcomes considered to show resistance, resilience, or susceptibility to severe neurological symptoms after long-term infection. For example, higher pre-infection measurement values for the Paw Drag parameter corresponded with greater disease severity at 90 d.p.i. Quantitative trait loci significantly associated with these DigiGait parameters revealed potential relationships between 28 differentially expressed genes (DEGs) and different aspects of gait influenced by viral infection. Thus, these potential candidate genes and genetic variations may be predictive of long-term neurological dysfunction. Overall, these findings demonstrate the predictive/prognostic value of quantitative and objective pre-infection DigiGait measurements for viral-induced neuromuscular dysfunction.

Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze 23-month old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) were housed under standard conditions, 3 mice per cage, with food and water ad libitum. Mice were injected intraperitoneally with 5-Aminoimidazole-4-carboxamide-1-a-D-ribofuranoside (AICAR, Toronto Research Chemicals Inc., Canada) dissolved in saline, 500 mg/kg/day for 3 (ACR3), 7 (ACR7) or 14 (ACR14) days or saline vehicle, for 3 (CTR) days. Thirty-three days after the final injection animals were deeply anesthetized with isofluorane and perfused transcardially with 0.9% NaCl solution. The gastrocnemius muscle and Hippocampus were quickly removed, frozen on dry ice and stored at M-bM-^HM-^R80 M-BM-0C for RNA isolation and microarray analysis.

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Project description:BackgroundFreezing in the levodopa-medicated-state (ON-state) is a debilitating feature of Parkinson's disease without treatment options. Studies detailing the distinguishing features between people with freezing of gait that improves with levodopa and those whose freezing continues even on levodopa are lacking.ObjectiveTo characterize the gross motor, gait, and non-motor features of this phenotype.MethodsInstrumented continuous gait was collected in the levodopa-medicated-state in 105 patients: 43 non-freezers (no-FOG), 36 with freezing only OFF-levodopa (OFF-FOG) and 26 with freezing both ON- and OFF-levodopa (ONOFF-FOG). Evaluation of motor and non-motor disease features was undertaken using validated scales. A linear mixed model with age, sex, disease duration, and motor UPDRS scores as covariates was used to determine differences in spatiotemporal gait and non-motor disease features among the groups.ResultsCompared to OFF-FOG, the ONOFF-FOG group had greater disease severity (on the Unified Parkinson's disease Rating Scale) and worse cognition (on the Montreal Cognitive Assessment, Frontal Assessment Battery and Scales for Outcome in Parkinson's disease-Cognition scales) and quality of life (on the PDQ-39), but similar mood (on the Hamilton depression and anxiety scales) and sleep quality (on Epworth sleepiness scale and RBD questionnaire). For several gait features, differences between the ONOFF-OFF groups were at least as large and in the opposite direction as differences between OFF-no groups, controlling for disease severity. Variability in ONOFF-FOG was greater than in other groups. Using results from our study and others, a power analysis for a potential future study reveals sample sizes of at least 80 ONOFF and 80 OFF-FOG patients would be needed to detect clinically meaningful differences.ConclusionsIntra-patient variability in spatiotemporal gait features was much greater in ONOFF-FOG than in the other two groups. Our results suggest that multifactorial deficits may lead to ONOFF-FOG development.

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Cognition and motor function: The gait and cognition pooled index.

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Cognition and motor function: The gait and cognition pooled index.

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