Stroke and APOE4 work together to increase dementia risk

Last Updated: 2008-01-10 10:46:06 -0400 (Reuters Health)

NEW YORK (Reuters Health) – Patients who have experienced a stroke and are also carriers of APOE4 are at increased risk for dementia compared with subjects with just one of these factors or neither, according to a report in the January 1st issue of Neurology.

The results of another study, reported in the same issue, indicate that NSAID use can reduce the risk of dementia in older adults, but only if they carry APOE4.

Dr. Y. P. Jin, from the University of Western Ontario in London, Canada, 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 1413 who participated in phase 2.

In both cohorts, the prevalence of dementia was highest in subjects with both stroke and APOE4 carriage.

The incidence of dementia in the median 4.6-year follow-up between CSHA-1 and CSHA-2 was 8.4 cases per 100 person-years among those with stroke and APOE4 compared with 4.3 per 100 person-years among the subjects having neither risk factor.

Hazard ratios for incident dementia with stroke alone, APOE4 carriage alone, and the presence of both were 1.33, 2.06, and 2.57, respectively, compared to the absence of both factors.

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 3229 subjects who participated in the Cardiovascular Health Cognition Study. The subjects, who were at least 65 years of age and dementia-free at baseline, were followed for 10 years.

Consistent with previous reports, NSAID use reduced the risk of Alzheimer’s disease, but not vascular dementia. On further analysis, however, the risk reduction was confined to carriers of APOE4 (adjusted hazard ratio = 0.34). There was no evidence that NSAIDs reported to selectively reduce amyloid-beta peptide 42, a more pathogenic amyloid variant, offered an advantage over other NSAIDs.

"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.

Neurology 2008;70:9-24.