Family history of dementia and brain health in childhood and middle age: a prospective community-based study

Abstract Objectives We aimed to determine the association of family history of dementia with structural brain measures and cognitive performance in childhood and mid-life adulthood. Methods We studied 1,259 parents (mean age: 47.3 years, standard deviation: 4.7) and 866 of their children (mean age 9.9 years standard deviation: 0.5) of the population-based Generation R Study. Parents filled in a questionnaire on family history, and both parents and children underwent cognitive assessment and neuroimaging. Results Of all participants, 109 parents (8.6%) reported a parental family history of dementia and 73 children (8.4%) had a grandparental history of dementia with mean age of dementia diagnosis in those affected 75 years (± 7.3) We observed no associations of dementia family history with cognitive ability in either parents or their children, except for worse manual dexterity in parents with a parental history of dementia, compared to those without (mean difference [95%CI]: -1.28 [-2.26; -0.30]). In parents and children, subclinical brain health did not differ significantly by family history. Results were consistent across age, sex, and APOEgenotype. Discussion Family history of dementia was associated with worse manual dexterity in mid-life adulthood, but not with any other measures of cognitive ability or subclinical brain health in childhood and mid-life. These findings suggest that the association of family history with dementia risk is due chiefly to neurodegenerative rather than neurodevelopmental processes, and might first present with motor deficits.