Intensive ‘Brain Training’ Intervention Fails to Reduce Amyloid Pathologies or Cognitive Deficits in Transgenic Mouse Models of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is aprogressive neurodegenerative disorder that is the leading cause of dementia in the elderly. Amyloid-β protein (Aβ) depositions in both the brain parenchyma and the cerebral vasculature are recognized as important pathological components that contribute to the cognitive impairments found in individuals with AD. Because pharmacological options have been minimally effective in treating cognitive impairment to date, interest in the development of preventative lifestyle intervention strategies has increased in the field. One controversial strategy, cognitive-specific stimulation, has been studied previously in human participants and has been widely commercialized in the form of 'brain-training games.' In the present study, we developed ahighly controlled, isolated cognitive training intervention program for mice. Two transgenic mouse lines, one that develops Aβ deposition largely in brain parenchyma, and another in the cerebral microvasculature, progressed through aseries of domain-specific tasks for an average of 4months. Despite the high intensity and duration of the intervention, we found little evidence of positive benefits for AD amyloid pathologies and post-training cognitive testing in these two models. Taken together, these results support the current evidence in human studies that cognitive-specific stimulation does not lead to ameasurable reduction in AD pathology or an improvement in general brain health.