Cognitive Reserve Gets More Backing as Dementia Hedge

STOCKHOLM, Oct. 2 -- A healthy cognitive reserve, deposited over a lifetime of learning, appears to protect the better-educated patients from dementia, investigators here suggested.

Among nearly 1,500 adults followed for more than 20 years, those who had at least six years of formal education had a significantly lower risk for any form of dementia and for Alzheimer's disease than adults who had five years of schooling or less, reported Tiia Ngandu, M.D., Ph.D., of the Karolinska Institute, and colleagues.

When they controlled for lifestyle choices such as poor diet or smoking that might contribute to dementia risk, the investigators found that education, or lack of it, remained a strong predictor of cognitive decline, they reported in the Oct. 2 issue of Neurology.

"Our results provide further firm evidence that the low educational level is related to the increased risk of dementia and Alzheimer's disease," they wrote. "We found that the association was independent of a wide range of other vascular and lifestyle related risk factors, and thereby provided evidence against the brain battering hypothesis. Educated persons may have greater cognitive reserve that leads to a postponement of the clinical manifestation of dementia."

The authors noted that many but not all cohort studies that have examined the question have detected an association between level of education and dementia risk, and three basic hypotheses suggesting an explanation for the link have emerged.

The brain reserve hypothesis, for examples, holds that people with higher levels have greater cognitive reserves, and therefore need to experience a higher degree of pathologic changes before dementia becomes evident, they noted.

"This brain reserve could be innate or due to early life factors, and high education would be a consequence of greater reserve," they wrote. "The concept of cognitive reserve adds a functional component to this hypothesis: higher reserve could be a more efficient use of existing networks, and it could be a result of both innate factors and lifelong mental stimulation."

Alternatively, better-educated people may exercise more and eat better than poorly educated people, and therefore be better protected from dementia risk factors such as cerebrovascular infarcts (the brain-battering hypothesis).

A third hypothesis suggests that diagnostic bias may play a role, because more highly schooled patients may score higher on dementia screening tests looking at cognitive ability, the authors noted.

The investigators looked at data on those who took part in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study.

Participants of the CAIDE study came from two towns in eastern Finland. They were chosen at random from population-based samples studied in a survey starting in 1972, with follow-up every five years. In the current study, the authors examined information on 1,449 men and women ranging in age from 65 to 79 who participated in a re-examination in 1998.

They found that compared with people with only five or fewer years of formal education, those who had six to eight years of schooling had an odds ratio for dementia of 0.57 (95% confidence interval 0.29 to 1.13), whereas those with nine years of education or more had an odds ratio of 0.16 (95% CI 0.06 to 0.41).

Similarly, compared with the least well educated group, participants with six to eight years of education had an odds ratio for Alzheimer's disease of 0.49 (95% CI 0.24 to 1.00) and those with nine or more years had an odds ratio of 0.15 (0.05 to 0.40).

In analyses controlling for possible confounders, including demographics and socioeconomic, vascular and lifestyle factors, the authors found that the associations between education and both all-cause dementia and Alzheimer's disease remained, with women and men being equally affected.

In addition, controlling for the presence of the apoliporotein E4 (ApoE4) allele, a known risk factor for early-onset Alzheimer's disease, did not modify the association. However, "among the ApoE4 noncarriers the risk of dementia was 0.44 (95% CI 0.16 to 1.17) for people with medium education, and 0.05 (0.01 to 0.38) for high education compared with that for low education in the model with full adjustments," the authors noted.

"As vascular factors contribute to the risk of dementia and AD, one of our hypotheses was that these factors could at least partly explain the effect of education on dementia," the authors wrote. "However, adjusting for midlife vascular and lifestyle related risk factors did not change the association between education and dementia."

They noted that in a model that included late-life comorbidities, the association between education and dementia was slightly weakened.

"People with low education also more often had stroke, myocardial infarction, diabetes, and more depressive symptoms," they wrote. "Thus, partly the effect of education could be mediated via these factors, or low education might lead to frailty and thereby increase the risk of both dementing and other late-life disorders."

The large population sample and high-degree of retention (72% of the original sample) are both strengths of the study, the authors said, but they did note a few limitations.

For example, the analyses are based on a sample of participants who survived until the 1998 reexamination, but "it is known that persons with low education also have higher mortality. If those who died between the examinations also were more often demented, then our results would underestimate the true association between education and dementia," they wrote.

They also were unable to determine whether factors that reflect brain maturation could account for at least some of the association between education and dementia (as suggested by the brain reserve hypothesis), because they lacked data on childhood IQ, socioeconomic status of parents, or maximal brain volume, the authors added.