Genetics and environmental determinants of Alzheimer's disease and related dementias in older Africans: a narrative review.

The burden of Alzheimer's disease and related dementias (ADRD) is rising in Africa, yet research remains limited compared to high-income regions. This narrative review investigated the genetic and environmental determinants of ADRD in older African populations, with a focus on the apolipoprotein E (APOE) gene. Although APOE ε4 is a strong risk factor for Alzheimer's disease globally, its role in African populations appears less pronounced and variable, likely due to genetic diversity, evolutionary adaptations, and environmental interactions. We discussed the epidemiology of dementia in Africa, contrasting urban and rural patterns, and examined the distribution and effects of APOE alleles across African regions. Additionally, we reviewed how environmental exposures-including malaria, hypertension, HIV, heavy metals, pesticides, vitamin D deficiency, and air pollution-interact with APOE genotypes to influence cognitive decline. Critical challenges such as healthcare disparities, diagnostic inconsistencies, and underrepresentation in genomic studies were highlighted. Finally, we emphasized the need for longitudinal, multicenter research and initiatives like the African Dementia Consortium to bridge knowledge gaps and inform culturally tailored interventions for dementia prevention and care in Africa.