Brain age gap, dementia risk factors and cognition in middle age

Brain Age Gap has been associated with dementia in old age. Less is known relating brain age gap to dementia risk-factors or cognitive performance in middle-age. Cognitively healthy, middle-aged subjects from PREVENT-Dementia had comprehensive neuropsychological, neuroimaging and genetic assessments. Brain Ages were predicted from T1-weighted 3T MRI scans. Cognition was assessed using the COGNITO computerized test battery. 552 middle-aged participants (median [interquartile range] age 52.8 [8.7] years, 60.0% female) had baseline data, of whom 95 had amyloid PET data. Brain age gap in middle-age was associated with hypertension ( P = 0.007) and alcohol intake ( P = 0.008) but not apolipoprotein E epsilon 4 allele ( P = 0.14), amyloid centiloids ( P = 0.39) or cognitive performance ( P = 0.74). Brain age gap in middle-age is associated with modifiable dementia risk-factors, but not with genetic risk for Alzheimer's disease, amyloid deposition or cognitive performance. These results are important for understanding brain-age in middle-aged populations, which might be optimally targeted by future dementia-preventing therapies.