Age is the primary risk factor for the development of Alzheimer’s disease (AD). Genetic factors may influence the development at a very early age. However, the etiology is unknown in the majority of patients and is likely due to a combination of both genetic and environmental factors. Only approximately 2% of Alzheimer’s cases are due to classical autosomal dominant genetic transmission. Three genes have been identified. These genes share a common biochemical pathway that leads to abnormal production of amyloid beta (a protein that accumulates in the brain of Alzheimer’s patients). ApoE, which plays an important role in cholesterol transport in the body, is a genetic factor that may influence amyloid toxicity and the age of onset of symptoms related to Alzheimer’s. Commercial testing for ApoE genotyping is available but not recommended in routine clinical practice as detection of the ApoE genotype is neither necessary nor sufficient to confirm a diagnosis.
Other potential midlife contributors to Alzheimer’s neuropathological changes include a history of head injury, obesity, insulin resistance (i.e., type 2 diabetes), hypertension, hyperlipidemia and obstructive sleep apnea. The clinical expression of disease may also be influenced by socioeconomic status as it relates to environmental enrichment and nutritional status. Prospective studies have confirmed the association between a higher risk of developing Alzheimer’s disease and subjects with lower educational attainment. Along these lines a recent study revealed that lifelong bilingualism appears to enhance cognitive reserve and delays the onset of symptoms of dementia. Specifically, patients who speak one language that were followed in this study became symptomatic at 72 years of age while those that were bilingual first became symptomatic at 78 years of age. Physical exercise in midlife has also been associated with reduced risk for the development of Alzheimer’s disease independent of other risk factors. Theoretically “cognitive exercise” may also reduce the risk for developing AD.
James W. Kozelka, M.D., Ph.D.
Board Certified Neurologist