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From Rush Alzheimer’s Disease Center and Rush Institute for Healthy Aging (Drs. Bennett, Wilson, Schneider, Evans, Mendes de Leon, Barnes, and Bienias) and Departments of Neurological Sciences (Drs. Bennett, Wilson, Schneider, Evans, and Barnes), Psychology (Drs. Wilson and Barnes), Pathology (Dr. Schneider), Internal Medicine (Drs. Evans, Mendes de Leon, and Bienias), and Preventive Medicine (Dr. Mendes de Leon), Rush Presbyterian-St. Luke’s Medical Center, Chicago, IL; and the Center for Neurobiology and Behavior (Dr. Arnold), University of Pennsylvania, Philadelphia.
Address correspondence and reprint requests to Dr. David A. Bennett, Rush Alzheimer’s Disease Center, 1645 W. Jackson, Suite 675, Chicago, IL 60612; e-mail: dbennett{at}rush.edu
Objective: To test the hypothesis that years of formal education modifies the relation of AD pathology to level of cognitive function.
Methods: A total of 130 older Catholic clergy participating in the Religious Orders Study underwent annual cognitive function testing and brain autopsy at the time of death. Individual cognitive function tests were z-scored and averaged to yield a global measure of cognitive function and summary measures of five different cognitive abilities. Neuritic and diffuse plaques and neurofibrillary tangles were counted in separate 1 mm2 areas of maximal density. Counts were converted to standard scores by dividing by their SD, and combined to yield a global AD pathology score and summary scores of each postmortem index. Linear regression was used to examine the relation of education and AD pathology scores to level of cognitive function proximate to death, controlling for age and sex. Subsequent analyses tested the interaction between education and each AD pathology score to determine whether education modified the relation of AD pathology to level of cognitive function. Additional analyses examined these associations on five specific cognitive abilities.
Results: Both years of formal education (regression coefficient = 0.073, p = 0.0001) and the global AD pathology score (regression coefficient = -0.689, p < 0.0001) were related to level of cognitive function. When an interaction term between education and AD pathology was added to the model, the association between a unit of AD pathology and level of cognitive function was 0.088 (p = 0.0078) standard unit less for each year of education than the level predicted from the model without the interaction term. Whereas neuritic plaques, diffuse plaques, and neurofibrillary tangles were all strongly related to cognitive function, education only modified the relation of neuritic plaques (p = 0.002) and diffuse plaques (p = 0.03) to cognition, but not neurofibrillary tangles. In analyses examining five different cognitive abilities, the interaction between education and the neuritic plaque score was strongest for perceptual speed and weakest for episodic memory.
Conclusions: These data provide strong evidence that the relation between senile plaques and level of cognitive function differs by years of formal education.
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