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

Article type: Research Article

Authors: Williams, Elizabeth^{a; 1} | Mutlu-Smith, Menekşe^{a; 1} | Alex, Ashli^{a; 2} | Chin, Xi Wei^{a; 2} | Spires-Jones, Tara^b | Wang, Szu-Han^{a; *}

Affiliations: [a] Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK | [b] Centre for Discovery Brain Sciences, UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK

Correspondence: [*] Correspondence to: Szu-Han Wang, Centre for Clinical Brain Sciences, The University of Edinburgh, 49 Little France Crescent, Edinburgh BioQuarter, Edinburgh, EH16 4SB, UK. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] These authors contributed equally to this work.

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

DOI: 10.3233/JAD-221185

Journal: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 683-704, 2023