The overall goal of this project is to deepen our understanding of aging processes and the aging brain in a community-based population. Our projects are thematically linked to an overarching hypothesis based on previous results from our own studies and the literature: that microinfarcts are key pathophysiological processes in late life brain dysfunction.
Aims 1 &2 will test hypotheses regarding 4 late-life brain outcomes: 1) Development of dementia and AD;2) Trajectories of global cognitive decline incorporating sophisticated modern psychometric analyses;3) Standard microscopic neuropathological measures;and 4) Novel biochemical neuropathological markers, including soluble A(S oligomers, markers of regional oxidative damage, and inflammatory markers.
Aim 1. Exploit unique clinical records to test hypotheses about the association between mid- and late-life micro- and macro-vascular conditions and late-life brain outcomes.
Aim 1 will take advantage of the >117,000 person-years of medical record data available from the cohort.
Aim la. Test hypotheses related to type 2 diabetes (DM). We will identify the independent and joint contributions of mid-life and late-life insulin resistance and hyperglycemia on late-life brain outcomes to determine whether these outcomes are best explained by insulin resistance, hyperglycemia, or both.
Aim lb. Test hypotheses related to renal disease. We will determine whether mid-life and late-life renal function is associated with greater risk for late-life brain outcomes.
Aim 1 c. Test hypotheses related to atrial fibrillation (AF). We will determine whether AF is associated with higher risk for late-life brain outcomes, whether increased persistence and duration of AF convey additional increased risk, and the extent to which anticoagulation ameliorates risks associated with AF.
Aim 2. Exploit unique ACT study research data to test hypotheses about the association between late-life measures of physical performance, frailty, and late-life brain outcomes. We will follow-up our preliminary finding that timed walk during life is associated with the presence of microinfarcts among autopsied participants to more fully test the hypotheses that decrements in timed walk and the development of frailty precede late-life brain outcomes.
Aim 3. Continue to serve as a valuable scientific resource and improve infrastructure to facilitate external use of ACT data.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AG006781-26S1
Application #
8890942
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7 (M2))
Program Officer
Anderson, Dallas
Project Start
1986-09-30
Project End
2015-08-31
Budget Start
2014-08-15
Budget End
2015-08-31
Support Year
26
Fiscal Year
2014
Total Cost
$652,628
Indirect Cost
$166,245
Name
Group Health Cooperative
Department
Type
DUNS #
078198520
City
Seattle
State
WA
Country
United States
Zip Code
98101
Beecham, Gary W; Hamilton, Kara; Naj, Adam C et al. (2014) Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias. PLoS Genet 10:e1004606
Escott-Price, Valentina; Bellenguez, CĂ©line; Wang, Li-San et al. (2014) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS One 9:e94661
Nelson, Peter T; Estus, Steven; Abner, Erin L et al. (2014) ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology. Acta Neuropathol 127:825-43
Postupna, Nadia O; Keene, C Dirk; Latimer, Caitlin et al. (2014) Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to Lewy body and Alzheimer's disease. Lab Invest 94:1161-72
Gross, Alden L; Sherva, Richard; Mukherjee, Shubhabrata et al. (2014) Calibrating longitudinal cognition in Alzheimer's disease across diverse test batteries and datasets. Neuroepidemiology 43:194-205
Ennis, Stephanie K; Larson, Eric B; Grothaus, Louis et al. (2014) Association of living alone and hospitalization among community-dwelling elders with and without dementia. J Gen Intern Med 29:1451-9
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
Benitez, Bruno A; Jin, Sheng Chih; Guerreiro, Rita et al. (2014) Missense variant in TREML2 protects against Alzheimer's disease. Neurobiol Aging 35:1510.e19-26
Brenowitz, Willa D; Hubbard, Rebecca A; Crane, Paul K et al. (2014) Longitudinal associations between self-rated health and performance-based physical function in a population-based cohort of older adults. PLoS One 9:e111761
Kim, Jong Hun; Song, Pamela; Lim, Hyunsun et al. (2014) Gene-based rare allele analysis identified a risk gene of Alzheimer's disease. PLoS One 9:e107983

Showing the most recent 10 out of 169 publications