Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam study
The apolipoprotein E4 allele (APOEɛ4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOEɛ4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE) score at follow-up was studied as a function of APOEɛ4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOEɛ4 and for APOEɛ4 in the absence of atherosclerosis. APOEɛ4 carriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference −0.7 points; 95% confidence interval −1.1 to −0.2) relative to non-APOEɛ4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOEɛ4 and atherosclerosis are not independent, and that particularly APOEɛ4 carriers with atherosclerosis are at increased risk of cognitive decline.
KeywordsCognitive Decline Common Carotid Artery APOE Genotype Mini Mental State Examination Score Rotterdam Study
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- American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd rev ed. DSM-III-R. American Psychiatric Association, Washington DCGoogle Scholar
- Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nature Genet 7: 180–184PubMedCrossRefGoogle Scholar
- Kida E, Pluta R, Lossinsky AS, Golabek AA, Choi-Miura N-H, Wisniewski HM, Mossakowski MJ (1995) Complete cerebral ischemia with short-term survival in rat induced by cardiac arrest. II. Extracellular and intracellular accumulation of apolipoproteins E and J in the brain. Brain Res 674: 341–346PubMedCrossRefGoogle Scholar
- Netherlands Central Bureau of Statistics (1987) Standard classification of education SOI-1978. Netherlands Central Bureau of Statistics, VoorburgGoogle Scholar
- Pedro-Botet J, Senti M, Nogués X, Rubiés-Prat J, Roquer J, D’Olhaberriague L, Olivé J (1992) Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. Stroke 23: 1556–1562PubMedCrossRefGoogle Scholar
- Stern Y, Brandt J, Albert M, Jacobs DM, Liu X, Bell K, Marder K, Sano M, Albert S, Del-Castillo Castenada C, Bylsma F, Tycho B, Mayeux R (1997) The absence of an apolipoprotein ∈4 allele is associated with a more aggressive form of Alzheimer’s disease. Ann Neurol 41: 615–620PubMedCrossRefGoogle Scholar
- Van Swieten JC, Van den Hout JH, Van Ketel BA, Hijdra A, Wokke JH, Van Gijn J (1991) Periventricular lesions in the white matter on magnetic resonance imaging in the elderly: a morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain 114: 761–774PubMedCrossRefGoogle Scholar