Explanations for familial stroke aggregation include differential phenotypic expression of apolipoprotein (a) and apolipoprotein E, racial variations in the distribution of vascular disease, identification of the autosomal-dominant disorder cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, specific point mutations in the mitochondrial-related disorders, and identification of the clinical significance of hereditable coagulopathies.
This population-based study indicates that apolipoprotein E polymorphism is not a risk factor for ischemic stroke in subjects aged > or = 75 years (although it might possibly influence survival after stroke occurrence and be a risk factor for infrequent hemorrhagic stroke) and that approximately 10% of cognitive impairment in this age group is attributable to stroke.
However, analysis of apoE genotypes as a function of stroke subtype revealed that the apoE4 allele was significantly more common in those patients with macroangiopathy-associated CVD.
Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages > or = 80 years (94 events).
In a multiple logistic regression analysis, age (P<.03), positive family history (P<.04) and apoE (P<.002) independently contributed to a stroke history, with epsilon4 carriers exhibiting a higher estimated risk (odds ratio, 5.05).
A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]).
The link between stroke and AD is probably higher than expected by chance for the following reasons: (i) both pathologies share genetic risk factors such as the epsilon 4 allele of the apolipoprotein E gene; (ii) AD patients have changes in the brain vessels that may lead to either ischemic or hemorrhagic stroke or white matter changes or both; (iii) there is evidence of an increased risk of stroke in AD patients; (iv) there is evidence of a frequent association of AD and stroke at autopsy.
The relative risk of dementia among parents according to the APOE-epsilon 4 status of probands, was calculated using a Cox model adjusted for the educational level of parents and their history of stroke: RR = 1.21 (95% CI 0.90, 1.63).
Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype.
Apolipoprotein E (ApoE) genotype, quantitative measures of brain volume, WMH, and the presence of stroke on MRI were obtained from the 396 participants in the final examination.
These differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of Alzheimer's disease and to the poor outcome after head trauma and stroke associated with apoE4 in humans.
We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population.
Cox proportional hazards regression models were constructed to estimate the risk for dementia in terms of relative risks (RRs) for stroke and the APOE epsilon4 allele, with adjustment for age, sex, education, systolic blood pressure, antihypertensive medication use, and heart disease.
We investigated the association between apoE genotypes and stroke subtypes by a case-control study in Bangladesh for the first time among south Asian countries.
Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.
The authors hypothesized that divergent influences of the APOE epsilon4 allele on ischemic and hemorrhagic stroke survival might result from differences in coagulation profiles.
The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOEepsilon3epsilon4 genotype.
The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE epsilon4/4 and APOE epsilon3/3 alleles in early-onset (< or =65 years old) and late-onset (>65 years old) groups.
In the different specific predisposition gene combinations, however, both the APOE 4 and MTHFR 677T alleles could increase the relative risk of the given stroke subgroup.