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Gene Mutation Plus Stroke Increase Dementia Risk
Neurology
January 1, 2008
Patients who have experienced a stroke and who are also carriers of APOE4, the gene mutation associated with an increase risk of Alzheimer's disease, have a greater risk of dementia compared with individuals with just one - or none -- of these factors, according to a report in the medical journal Neurology.
The results of another study, also reported in Neurology, indicate that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of dementia in older adults, but only if they carry APOE4. NSAIDs include drugs such as aspirin, ibuprofen and naproxen.
Dr. Y. P. Jin, from the University of Western Ontario, London, and colleagues assessed the joint effect of stroke and APOE4 on dementia risk by analyzing data from 949 subjects who participated in phase 1 of the Canadian Study of Health and Aging (CSHA) and 1,413 who participated in phase 2.
In both groups, the prevalence of dementia was highest in subjects who had a stroke and were APOE4 carriers. For instance in CHSA-2, the presence of both factors was associated with a dementia prevalence of 57.6 percent, while individuals without either factor had a dementia prevalence of 23.3 percent.
The incidence of dementia in the time between CSHA-1 and CSHA-2, an average of 4.6 years, was 8.4 cases per 100 persons per year for individuals with stroke and APOE4 compared with 4.3 cases per 100 persons per year among those without either risk factor.
Compared with those without either risk factor, the dementia risk for those with stroke alone was 33 percent higher and for those with APOE4 alone, the dementia risk was increased by two-fold. Individuals with both factors had 2.5-times the dementia risk.
In the second study, Dr. P. P. Zandi, from Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues, examined the impact that NSAID use had on dementia risk in 3,229 subjects who participated in the Cardiovascular Health Cognition Study. The subjects, who were at least 65 years of age and dementia-free at the start of the study, were followed for 10 years.
Consistent with previous reports, NSAID use reduced the risk of Alzheimer's disease, but not vascular dementia (dementia caused by restriction of blood flow to the brain, which starves the brain tissue of oxygen). On further analysis, however, the risk reduction was confined to APOE4 carriers.
"These findings should provide important clues for studies of the underlying biology of dementia and Alzheimer's disease," Dr. Joseph Rogers and Dr. Marwan N. Sabbagh, from the Sun Health Research Institute in Sun City, Arizona, comment in a related editorial.
Regardless of how APOE4 increases the risk of Alzheimer's disease, the results of the first study suggest that it is "independent of the cerebrovascular and other changes that make stroke a risk factor for dementia," while those of the second suggest that it is "ameliorated by NSAIDs," the editorialists note.
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