By Elizabeth Mormino, PhD, Stanford University, SWHR Interdisciplinary Network on Alzheimer’s Disease Member
The long course of Alzheimer’s disease: Put simply, Alzheimer’s disease (AD) can be conceptualized as two stages: a clinically silent stage, where brain pathologies are present, but symptoms are absent; and a symptomatic stage, where individuals show signs of dementia (this typically involves memory impairment as well as an inability to live independently). Although there is debate regarding what criteria should be used to classify the clinically silent stage, there is consensus in the field that the pathological drivers of AD, the brain accumulation of amyloid and tau proteins, begin decades before symptoms occur. We can measure these pathologies in humans by using either brain scans or lumbar puncture. Research studies have shown that individuals with no symptoms of dementia but who have evidence of AD pathology are at elevated risk for being diagnosed with AD during a later follow-up visit. These individuals with evidence of pathology but no symptoms are currently being targeted in prevention trials to determine if reducing pathology during the clinically silent stage prevents symptoms of dementia. Given the failure of multiple clinical trials in symptomatic AD patients, there is hope that targeting the disease as early as possible, even before symptoms are present, will be a successful strategy against AD.
Risk factors for AD: Despite the fact that over 5 million Americans currently live with AD, it is very difficult to predict who will develop the disease. The most established risk factors are older age and the presence of the APOE4 gene (possession of the APOE4 genotype is known to increase amyloid buildup in the brain). Interestingly, some work has suggested that women are more at risk for AD than men, even after accounting for women’s longer lifespans. However, a greater incidence of AD is not always identified in studies, suggesting that if women are at elevated risk of AD compared to men, the reasons are complex and multifactorial.
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