Lifestyle activities in mid-life contribute to cognitive reserve in middle-aged individuals at risk for late-life Alzheimer's disease, independent of education and occupation

It is now acknowledged that Alzheimers disease (AD) neuropathology starts decades before the onset of clinical symptoms, but it remains unknown whether modifiable lifestyle factors can protect against these incipient AD processes, early, in mid-life. Cognitive reserve can explain cognitive preservation in some older adults despite ageing or dementia symptoms, but it is not known whether it can protect against neurodegeneration in mid-life. We asked whether modifiable lifestyle activities contribute to cognitive reserve in mid-life, and whether it can offset the risk of AD in individuals who are cognitively healthy. Cognition, structural, and functional brain health measures were assessed at baseline and two years follow-up, in a cohort of middle-aged participants (N = 210; 40-59 years). Mid-life activities were measured using the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities and known risk factors for sporadic late-onset AD (i.e., the Cardiovascular Risk Factors Aging and Dementia [CAIDE] score) on measures of cognition and brain health. Multivariable linear regression found that mid-life activities made a unique contribution to cognition, independent of education and occupation. Crucially, mid-life activities moderated the relationship between cognitive ability (verbal and visuospatial functions, and conjunctive short-term memory binding) and brain health. Cognitive ability of people with higher mid-life activities, particularly those with high dementia risk scores, was less dependent on their brain functional architecture. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously been associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. These findings suggest that modifiable activities contribute uniquely to cognitive reserve in midlife, and may offset the risk of AD. The modifiability of these activities supports their targeting by public health initiatives aimed at dementia prevention.