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  • Title: Mid-Adulthood Cognitive Training Improves Performance in a Spatial Task but Does Not Ameliorate Hippocampal Pathology in a Mouse Model of Alzheimer's Disease.
    Author: Williams E, Mutlu-Smith M, Alex A, Chin XW, Spires-Jones T, Wang SH.
    Journal: J Alzheimers Dis; 2023; 93(2):683-704. PubMed ID: 37066912.
    Abstract:
    BACKGROUND: Prior experience in early life has been shown to improve performance in aging and mice with Alzheimer's disease (AD) pathology. However, whether cognitive training at a later life stage would benefit subsequent cognition and reduce pathology in AD mice needs to be better understood. OBJECTIVE: This study aimed to verify if behavioral training in mid-adulthood would improve subsequent cognition and reduce AD pathology and astrogliosis. METHODS: Mixed-sex APP/PS1 and wildtype littermate mice received a battery of behavioral training, composed of spontaneous alternation in the Y-maze, novel object recognition and location tasks, and spatial training in the water maze, or handling only at 7 months of age. The impact of AD genotype and prior training on subsequent learning and memory of aforementioned tasks were assessed at 9 months. RESULTS: APP/PS1 mice made more errors than wildtype littermates in the radial-arm water maze (RAWM) task. Prior training prevented this impairment in APP/PS1 mice. Prior training also contributed to better efficiency in finding the escape platform in both APP/PS1 mice and wildtype littermates. Short-term and long-term memory of this RAWM task, of a reversal task, and of a transfer task were comparable among APP/PS1 and wildtype mice, with or without prior training. Amyloid pathology and astrogliosis in the hippocampus were also comparable between the APP/PS1 groups. CONCLUSION: These data suggest that cognitive training in mid-adulthood improves subsequent accuracy in AD mice and efficiency in all mice in the spatial task. Cognitive training in mid-adulthood provides no clear benefit on memory or on amyloid pathology in midlife.
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