This R21 application, entitled ?Primary prevention, life expectancy, and years lived with and without Alzheimer?s dementia in the United States,? is a new submission in response to PA-17-089. A recent 2-year double-blinded, randomized controlled trial, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), demonstrated that interventions on multiple domains, such as diet, exercise, and cognitive training contribute to an improved of cognitive functioning in older adults. Because there is no cure for Alzheimer?s dementia prevention has become the highest priority for investigators around the world. Therefore, several clinical trials around the world, including U.S POINTER in the United States, are focusing on primary prevention of Alzheimer?s dementia through modification of lifestyle factors. Positive findings from these clinical trials would have paramount importance for public health because, in the absence of treatment, these interventions will be prescribed as tools to prevent cognitive impairment in a vulnerable population of older adults. However, in addition to attenuating dementia risk, these lifestyle factors contribute to an increase in life expectancy. We have recently shown that adherence to a healthy lifestyle at age 50 is associated with a prolonged life expectancy by 12.2 and 14.0 years for men and women living in the United States. Given that age is the most critical risk factor for Alzheimer?s dementia (e.g., rates of Alzheimer?s dementia increases exponentially with increasing age), it raises the concern if these multidomain interventions could postpone Alzheimer?s dementia to later ages, but the overall years lived with the disease might not change. If that is the case, then health professionals, policy-makers, and stakeholders must be informed in time to plan future health care costs and health care needs adequately. To date, no efforts have been made to quantify the years of life an individual can expect to live with and without Alzheimer?s dementia according to the adherence to lifestyle factors. We will investigate the impact of multidomain lifestyle factors that include diet, exercise, and cognitive training on life expectancy with and without Alzheimer?s dementia based on data from 18 years of follow-up in the Chicago Health and Aging Project and 21 years of follow-up in the Memory and Aging Project. This foundational study has the potential: (1) to estimate the number of years that an individual will live with and without Alzheimer?s dementia during lifespan; (2) to evaluate whether postponing Alzheimer?s dementia onset through multidomain interventions could influence total years lived with Alzheimer?s dementia across the lifespan; (3) to determine whether genetic factors, including APOE e4 allele variation, impacts the role of lifestyle factors on prevention of Alzheimer?s dementia; (4) to evaluate the role of brain amyloid-beta and neuritic plaque on years lived with and without Alzheimer?s dementia to address the question of why some individuals do not experience Alzheimer?s dementia during lifespan despite the significant burden of pathology in the brain.
A combination of a healthy diet, physical activity, and stimulating cognitive activities has been proposed as a promising strategy to maintain a healthy brain, and postpone or even prevent Alzheimer?s dementia. Previous studies indicate that adherence to a healthy lifestyle is associated with prolonged life expectancy by 12.2 and 14.0 years for men and women living in the United States. This application proposes to investigate whether postponing Alzheimer?s dementia onset through modifiable lifestyle factors (e.g., diet, physical activity, and cognitive training) could influence total years lived with and without Alzheimer?s dementia across the lifespan, using data from extensive and well-characterized cohort studies, the Chicago Health and Aging Project and Rush Memory and Aging Project.
