Mn. Haan et al., The role of APOE epsilon 4 in modulating effects of other risk factors forcognitive decline in elderly persons, J AM MED A, 282(1), 1999, pp. 40-46
Citations number
59
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Context Cognitive decline in elderly persons is often an early predictor of
dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus m
ay contribute to substantial decline in cognitive function in the elderly.
These risks may be modified by gene-environment interactions between apolip
oprotein E (APOE) genotype and CVD risk factors or subclinical CVD.
Objectives To examine the association between subclinical CVD and decline i
n cognitive functioning in the elderly and to examine effect modification b
y the APOE genotype of the association between subclinical disease and cogn
itive decline.
Design The Cardiovascular Health Study, a population-based, prospective coh
ort study.
Setting and Population A total of 5888 randomly selected Medicare-eligible
participants from Sacramento County, California; Forsyth County, North Caro
lina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or old
er, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) a
nd who were followed up for 7 and 5 years, respectively.
Main Outcome Measures Change over time in scores on the Modified Mini-Menta
l State Examination and the Digit Symbol Substitution Test as a function of
APOE genotype, subclinical CVD, and diabetes mellitus.
Results Seventy percent of participants had no significant decline on the M
odified Mini-Mental State Examination. Systolic blood pressure, the ankle-a
rm brachial index, atherosclerosis of the internal carotid artery, diabetes
mellitus, and several diagnoses of prevalent CVD were significantly associ
ated with declines in scores on the Modified Mini-Mental State Examination
and the Digit Symbol Substitution Test. The rate of cognitive decline assoc
iated with peripheral vascular disease, atherosclerosis of the common and i
nternal carotid arteries, or diabetes mellitus was increased by the presenc
e of any APOE epsilon 4 allele.
Conclusions Most healthy elderly people did not experience cognitive declin
e. Measures of subclinical CVD were modest predictors of cognitive decline.
Those with any APOE epsilon 4 allele in combination with atherosclerosis,
peripheral vascular disease, or diabetes mellitus were at substantially hig
her risk of cognitive decline than those without the APOE epsilon 4 allele
or subclinical CVD. High levels of atherosclerosis increased cognitive decl
ine independently of APOE genotype.