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: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.

Dataset Information

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

Publications

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

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