Dementia in the elderly is a chronic syndrome with multiple causes that is already major public health burden and presents a clear therapeutic imperative to biomedical researchers. Given the time and expense of randomized clinical trials (RCTs) focused on preventing or delaying incident dementia, there is a critical public health need to validate therapies quickly and robustly to insure that the best possible candidates advance to RCTs. This application is a competitive renewal of Pharmaco- neuropathology of Brain Aging and Dementia that exploits the tremendous and unique resources of the Adult Changes in Thought Study, a large population-based longitudinal study of brain aging and incident dementia in older individuals, to identify potentially effective therapeutics for advancement to clinical trials. In this competitive renewal, we propose to determine the associations between the following mid- and late-life exposures or activities and neuropathologic, structural, and biochemical features of dementia in the elderly: """"""""cardioprotective"""""""" doses of aspirin, hormone replacement therapy in women, two subclasses of antihypertensive drugs with proposed neuroprotective actions (calcium channel blockers and angiotensin-converting enzyme inhibitors), and level of physical exercise. These observational data will provide a unique perspective on which commonly prescribed drugs or exercise suppress specific mechanisms of disease, thereby guiding research on comparative effectiveness and aiding in the selection of regimens to pursue in RCTs.

Public Health Relevance

Dementia in the elderly is a major and growing public health burden with a clear therapeutic imperative. There are several causes of dementia that can only be definitively diagnosed by autopsy. The goal of this project is to identify potentially effective, commonly used drugs or interventions that are associated with reduced risk of the changes of these different causes of dementia in brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG023801-07
Application #
8241022
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Anderson, Dallas
Project Start
2004-04-01
Project End
2016-02-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
7
Fiscal Year
2012
Total Cost
$321,438
Indirect Cost
$91,877
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Dublin, Sascha; Anderson, Melissa L; Heckbert, Susan R et al. (2014) Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort. J Gerontol A Biol Sci Med Sci 69:609-15
Montine, Thomas J; Sonnen, Joshua A; Montine, Kathleen S et al. (2012) Adult Changes in Thought study: dementia is an individually varying convergent syndrome with prevalent clinically silent diseases that may be modified by some commonly used therapeutics. Curr Alzheimer Res 9:718-23
Postupna, Nadia; Rose, Shannon E; Bird, Thomas D et al. (2012) Novel antibody capture assay for paraffin-embedded tissue detects wide-ranging amyloid beta and paired helical filament-tau accumulation in cognitively normal older adults. Brain Pathol 22:472-84
Back, Stephen A; Kroenke, Christopher D; Sherman, Larry S et al. (2011) White matter lesions defined by diffusion tensor imaging in older adults. Ann Neurol 70:465-76
Sonnen, Joshua A; Santa Cruz, Karen; Hemmy, Laura S et al. (2011) Ecology of the aging human brain. Arch Neurol 68:1049-56
Naj, Adam C; Jun, Gyungah; Beecham, Gary W et al. (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet 43:436-41
SantaCruz, Karen S; Sonnen, Joshua A; Pezhouh, Maryam Kherad et al. (2011) Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study. J Neuropathol Exp Neurol 70:832-40
Tsuang, Debby; Larson, Eric B; Li, Ge et al. (2010) Association between lifetime cigarette smoking and lewy body accumulation. Brain Pathol 20:412-8
Sonnen, J A; Larson, E B; Walker, R L et al. (2010) Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques. Neurology 75:1203-10
Sonnen, Joshua A; Postupna, Nadia; Larson, Eric B et al. (2010) Pathologic correlates of dementia in individuals with Lewy body disease. Brain Pathol 20:654-9

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