Our purpose is to gain a better understanding of the causes of cognitive decline and dementia through the study of brain structures at death in approximately 280 autopsied men whose health, illnesses, cognitive functioning, genetic and physiologic constitution, and midlife exposures to a long list of personal and environmental factors have been prospectively defined through repeated interview and examination over a 30+ year interval. When added to similar data already collected with prior funding (from an NIA contract) the total number of autopsies available for analysis will be approximately 640. The subjects are Japanese-American men in Hawaii aged 78+ years at death who have participated in the Honolulu Heart Program since it began in 1965. The methods for defining structural features will include gross autopsy, microscopic examination, and MRI examination of the fixed brain before dissection. Prior to fixation, multiple samples of brain tissue and CSF will be removed and frozen for future study. The specific structural endpoints to be studied include densities of neurofibrillary tangles, senile plaques, neuritic plaques, and Lewy bodies; small vessel strokes, large vessel strokes, defined changes in arterial wall architecture (medium and small vessels); brain size/atrophy (segmented into gray and white matter), and volumes of specified brain regions (hippocampus, amygdala, mesial temporal lobe, total neocortex). Analyses will be focused on: (1) autopsy verification of clinical diagnoses of dementia, (2) development of """"""""new"""""""" neuropathologic criteria for vascular dementia, (3) identification of risk factors predicting Alzheimer's disease, vascular dementia, and the individual structural endpoints mentioned, and (4) inter-relationships among the structural endpoints as they reflect interacting processes involved ~n the pathogenesis of dementia. All methods used will allow comparisons with corresponding data generated by another study in European-ancestry women (the Nun Study). All information and materials will be archived for future research use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG017155-02
Application #
6372389
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Anderson, Dallas
Project Start
2000-06-01
Project End
2005-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
2
Fiscal Year
2001
Total Cost
$806,804
Indirect Cost
Name
Kuakini Medical Center
Department
Type
DUNS #
City
Honolulu
State
HI
Country
United States
Zip Code
96817
Abbott, R D; Nelson, J S; Ross, G W et al. (2017) Marinesco bodies and substantia nigra neuron density in Parkinson's disease. Neuropathol Appl Neurobiol 43:621-630
Abbott, Robert D; Ross, G Webster; Petrovitch, Helen et al. (2016) Midlife milk consumption and substantia nigra neuron density at death. Neurology 86:512-9
Gelber, Rebecca P; Redline, Susan; Ross, G Webster et al. (2015) Associations of brain lesions at autopsy with polysomnography features before death. Neurology 84:296-303
Ross, G Webster; Abbott, Robert D; Petrovitch, Helen et al. (2012) Pre-motor features of Parkinson's disease: the Honolulu-Asia Aging Study experience. Parkinsonism Relat Disord 18 Suppl 1:S199-202
Ross, G Webster; Duda, John E; Abbott, Robert D et al. (2012) Brain organochlorines and Lewy pathology: the Honolulu-Asia Aging Study. Mov Disord 27:1418-24
de Jong, L W; Wang, Y; White, L R et al. (2012) Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study. Neurobiol Aging 33:424.e1-10
Milber, Joshua M; Noorigian, Joseph V; Morley, James F et al. (2012) Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease. Neurology 79:2307-14
Abbott, Robert D; Ross, G Webster; Tanner, Caroline M et al. (2012) Late-life hemoglobin and the incidence of Parkinson's disease. Neurobiol Aging 33:914-20
Abbott, Robert D; Kadota, Aya; Miura, Katsuyuki et al. (2011) Impairments in activities of daily living in older Japanese men in hawaii and Japan. J Aging Res 2011:324592
Rocca, Walter A; Petersen, Ronald C; Knopman, David S et al. (2011) Trends in the incidence and prevalence of Alzheimer's disease, dementia, and cognitive impairment in the United States. Alzheimers Dement 7:80-93

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