People aged 90 years and older (the oldest-old) are the fastest growing segment of the U.S. population and suffer from high rates of dementia, a disease involving memory and other thinking problems associated with functional loss. Dementia is associated with poor health outcomes and high health care costs, as well as a heavy burden on caregivers, the health care system, and society. Identification and treatment of modifiable risk factors of dementia is essential to ease the coming public health crisis particularly in the rapidly growing age group of the oldest-old. It has been suggested that high cholesterol, effectively treated with statin medications, may be a modifiable risk factor of dementia. It is unclear if high cholesterol and statin use is protective or detrimental towards developing dementia in people aged 90 years and older. The 90+ Study is a large population-based longitudinal study of aging and dementia in the oldest-old. Recently, we found that statin use in the oldest-old is significantly associated with a 33% to 57% decrease in development of dementia over an average of three years, regardless of reported history of high cholesterol. Statins may be acting on dementia risk through a variety of mechanisms beyond cholesterol-lowering, including impaired production of the abnormal beta amyloid plaques associated with dementia and protection against vascular events. Thus, the goal of the proposed research plan is to extend our previous findings and evaluate four possible explanations for the association between statin use and decreased dementia risk in the oldest-old, using data collected by The 90+ Study. It is possible that one, some, or all mechanism may play an explanatory role. First, we will evaluate if the competing risk of mortality accounts for the association between statin use and decreased dementia risk (Aim 1), which if true would suggest that statin use is not the true explanation behind the previous finding. We will then examine whether blood cholesterol levels measured at age 90+ account for the association between statin use and decreased dementia risk (Aim 2), which if true would suggest that statins are actin by cholesterol-lowering. We will use autopsy data to determine if statin use is associated with dementia-associated neuropathology (amyloid vs vascular), and if so whether neuropathology accounts for the association between statin use and decreased dementia risk (Aim 3). Last, we will use brain imaging (florbetapir amyloid PET and structural MRI and) to evaluate if statin use is associated with dementia- associated neuropathology in living participants and if so, what type of neuropathology (amyloid measured on PET or vascular measured on MRI) (Aim 4). Understanding how statin use benefits dementia risk in the oldest-old may have important public health implications for the management of cardiovascular risk factors in relation to brain health in this rapidly growing segment of the population.
People aged 90 and older (the oldest-old) are the fastest growing segment of the United States population, and suffer from the highest rates of dementia. This proposal seeks to explore potential explanations for how statin cholesterol-lowering drugs are related to lower dementia risk in the oldest-old. Understanding these explanations could potentially aid in discovering methods to prevent or delaying dementia in our oldest-old citizens, which would have an enormous public health impact in terms of quality of life, health care costs, and caregiver burden.
| Nolen, Shantell C; Evans, Marcella A; Fischer, Avital et al. (2017) Cancer-Incidence, prevalence and mortality in the oldest-old. A comprehensive review. Mech Ageing Dev 164:113-126 |
