A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality

Abstract

Objectives-To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. Methods-A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. Results-At the age of 85, carriers of the apoE 4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE 4 allele was associated with mixed Alzheimer's diseasemulti-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE 4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE 4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE 4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The 2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multiinfarct dementia during the follow up (OR 2.9; p<0.05). Conclusions-Neither the apoE 4 allele nor white matter lesions are suYcient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia substantially.(J Neurol Neurosurg Psychiatry 1998;64:37-43)

Incidence of Dementia in Relation to Stroke and the Apolipoprotein E ε4 Allele in the Very Old

“…[23][24][25][26][27][28] In the present longitudinal study, the APOE ⑀4 allele did not significantly increase the risk of dementia with stroke, in disagreement with a previous casecontrol study. 11 It has been shown that the APOE ⑀4 allele is related to early death, 52 especially in those with good cognition.…”

“…11,17,19 -28 In some studies, the APOE ⑀4 allele has been associated with increased risk of vascular dementia, 11,17,20 -22 but other studies have failed to confirm this association. [23][24][25][26][27][28] Finally, an ethnic variation of the APOE effect on dementia has been reported. The APOE ⑀4 allele is not a significant risk factor for AD among blacks and Hispanics.…”

Genetic Determinants of White Matter Hyperintensities on Brain Scans

“…14 -36,48 Eleven compared the numbers of individuals in lower and upper WMH grades between genotype groups ( Figure 1A), 14,16,17,22,23,25,29,30,33 3 compared mean grade ( Figure 1B), 15,21,24 and 4 compared mean volume ( Figure 1C). 20,28,34 Random-effects meta-analyses comparing 4ϩ with 4Ϫ genotypes found no evidence of association between APOE and WMH (graded WMH dichotomous pooled OR, 0.97; 95% CI, 0.78 -1.21; graded WMH continuous pooled standardized mean difference: 0.30, 95% CI, Ϫ0.02-0.62; WMH volume pooled standardized mean difference: 0.15, 95%CI Ϫ0.04 to 0.33).…”

Familial Alzheimer disease in Latinos

“…Although APOE genotype was not considered, data from the Cache County Study (30) support the findings of increased stroke-associated risk of AD in the presence of vascular risk factors. The presence of APOE-ε4 has been shown to be a risk factor for dementia with stroke in two population-based casecontrol studies (31,32).…”