Repeated multi-domain, but not single-domain, cognitive training prevents cognitive decline and amyloid pathology found in the APP^NL-G-F mouse model of Alzheimer disease

Abstract

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may prevent/ or delay the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate this protective effect, APPNL-G-F/NL-G-F mice at 3 months of age were exposed to repeated, single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, 9 & 12 months of age. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for cognitive training groups and control group. After completion of behavioral testing, mice were sacrificed, and their brains were assessed for pathology. AppNL-G-F mice given multi-domain cognitive training compared to APPNL-G-F control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. There were mild reductions in microglosis in the brain of APPNL-G-F mice with singledomain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.