The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on cognitive impairment

Abstract

The Honolulu-Asia Aging Study (HAAS) is a longitudinal epidemiologic investigation of rates, risk factors, and neuropathologic abnormalities associated with cognitive decline and dementia in aged Japanese-American men. The project was established in 1991 and will be brought to closure in 2012. Age-specific rates of total dementia and the major specific types of dementia in HAAS participants are generally similar to those reported from other geographic, cultural, and ethnic populations. Risk factors for dementia in the HAAS include midlife hypertension and other factors previously shown to influence cardiovascular disease. The autopsy component of the project has yielded novel findings, the most illuminating of which is the demonstration of 5 important lesion types linked independently to cognitive impairment. While one of these--generalized atrophy--is strongly associated with both Alzheimer lesions and microinfarcts, it also occurs in the absence of these lesions and is independently correlated with dementia. Each lesion type is viewed as representing a distinct underlying pathogenic process. Their summed influences is an especially robust correlate of dementia in the months and years prior to death.

Fig. (1)

Cumulative analysis of variance, dependent variable: final CASI score before death. Percentages refer to percent of variance in the final CASI score explained by the model with entry of explanatory variables beginning at 12 o'clock with education and progressing sequentially clockwise.

Fig. (2)

Cumulative analysis of variance identical to Fig. (1), except with altered order of entry of the predictor variables with ‘atrophy’ entered after isocortical Lewy bodies, and before Alzheimer lesions.

Fig. (3)

Cumulative analysis of variance identical to Figs. (1) and (2), except for entry of ‘atrophy’ after education and prior to all other predictor variables.