Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: The ARIC MRI Study

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
Alzheimer's & dementia: the journal of the Alzheimer's Association (Impact Factor: 12.41). 04/2009; 5(3):207-14. DOI: 10.1016/j.jalz.2009.01.027
Source: PubMed


Strokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited.
We describe the relationships of APOE genotype, stroke, and vascular risk factors with cognitive change over a 14-year follow-up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age.
Participants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990-1992 and 2004-2006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990-1992. Incident stroke was recorded over the 14 years of follow-up.
There were 1130 participants (mean age, 59 +/- 4.3 [SD] years; 62% women; 52% African-American) with longitudinal data. In multivariate, random-effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE epsilon4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not. For DWR, stroke and APOE epsilon4 genotype were independent predictors of decline (both P < .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all P < .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found.
The vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE epsilon4 genotype independently contribute to cognitive decline in late middle age and early elderly years.

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    • "Among individual risk factors, only diabetes was associated independently with cognitive decline. Although this association has not been found in some studies [21], the observed relation between diabetes and cognitive decline in our study is supported by a number of studies reporting associations of diabetes with longitudinal changes on magnetic resonance imaging markers of vascular brain injury [17], incident cognitive impairment and cognitive decline [13] [36] [37], and incident dementia [38]. There is compelling evidence for a causal relationship between alterations in glycemic control and subsequent brain ischemic and atrophic changes [39]. "
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    ABSTRACT: Background: Stroke is associated with an increased risk of dementia. However, it is unclear whether risk of stroke in those free of stroke, particularly in nonelderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in mid life is associated with cognitive decline over 10 years of follow-up. Methods: We studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP), which incorporates age, sex, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over 10 years. Longitudinal associations between FSRP and its components were tested using mixed-effects models, and rates of cognitive change over 10 years were estimated. Results: Higher stroke risk was associated with faster decline in verbal fluency, vocabulary, and global cognition. For example, for global cognition there was a greater decline in the highest FSRP quartile (-0.25 of a standard deviation; 95% confidence interval: -0.28 to -0.21) compared with the lowest risk quartile (P = .03). No association was observed for memory and reasoning. Of the individual components of FSRP, only diabetes mellitus was associated independently with faster cognitive decline (β = -0.06; 95% confidence interval, -0.01 to 0.003; P = .03). Conclusion: Elevated stroke risk at midlife is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.
    Full-text · Article · Nov 2012 · Alzheimer's & dementia: the journal of the Alzheimer's Association
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