Mid-Adulthood Cognitive Training Improves Performance in a Spatial Task but Does Not Ameliorate Hippocampal Pathology in a Mouse Model of Alzheimer's Disease

J Alzheimers Dis. 2023;93(2):683-704. doi: 10.3233/JAD-221185.

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.

Keywords: Aging; Alzheimer’s disease; amyloid-β; astrocytes; cognitive reserve; dementia; hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cognitive Training
  • Disease Models, Animal
  • Gliosis / pathology
  • Gliosis / therapy
  • Hippocampus / pathology
  • Humans
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Amyloid beta-Peptides