Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis ( n = 27 probable/possible Alzheimer’s disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia.

While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele [ 1 ] failed to find any effect of the *E4 allele on cognitive performance at ages 20–24, 40–44 or 60–64 years. In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65–69 years. Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change. It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.