Genetic and Nongenetic Risk Factors for Dementia

Dementia has been linked to senility since ancient times. Research shows that interventions promoting healthy nutrition, physical activity, and cognitive training can maintain cognitive function. Genetic and modifiable risk factors contribute to dementia development, but their interaction remains complex. Genetics play a significant role in determining an individual’s vulnerability to dementia, accounting for over half the variation in susceptibility. Researchers have focused on Alzheimer’s disease (AD) over the past three decades, with the first genetic insight into autosomal dominant forms of AD being the discovery of three genes: APP, PSEN1, and PSEN2. Next-generation sequencing has identified over 70 more common genetic variants associated with AD. Understanding the functional genomics of dementia risk loci will help uncover new targets for prevention and treatment. The 2020 Lancet Commission found that addressing 12 modifiable risk factors could prevent 40% of dementia cases, but the complex interaction between genetic predisposition and risk factors remains unexplored. This chapter examines the role of specific prominent genes in Alzheimer’s disease pathogenesis, as well as modifiable risk factors like education, hypertension, diabetes, physical activity, and hearing impairment.