Association of Life Activities With Cerebral Blood Flow in Alzheimer Disease: Implications for the Cognitive Reserve Hypothesis

Scarmeas, Nikolaos; Zarahn, Eric; Anderson, Karen E.; Habeck, Christian G.; Hilton, H. John; Flynn, Joseph; Marder, Karen; Bell, Karen L.; Moeller, James R.; Sackeim, Harold A.; Van Heertum, Ronald L.; Stern, Yaakov

Background: Regional cerebral blood flow (CBF), a good indirect index of cerebral pathologic changes in Alzheimer disease (AD), is more severely reduced in patients with higher educational attainment and IQ when controlling for clinical severity. This has been interpreted as suggesting that cognitive reserve allows these patients to cope better with the pathologic changes in AD. Objective: To evaluate whether premorbid engagement in various activities may also provide cognitive reserve. Design: We evaluated intellectual, social, and physical activities in 9 patients with early AD and 16 healthy elderly controls who underwent brain H₂^(15)O positron emission tomography. In voxelwise multiple regression analyses that controlled for age and clinical severity, we investigated the association between education, estimated premorbid IQ, and activities, and CBF. Results: In accordance with previous findings, we replicated an inverse association between education and CBF and IQ and CBF in patients with AD. In addition, there was a negative correlation between previous reported activity score and CBF in patients with AD. When both education and IQ were added as covariates in the same model, a higher activity score was still associated with more prominent CBF deficits. No significant associations were detected in the controls. Conclusions: At any given level of clinical disease severity, there is a greater degree of brain pathologic involvement in patients with AD who have more engagement in activities, even when education and IQ are taken into account. This may suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between brain damage and the clinical manifestation of AD.


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Taub Institute
American Medical Association
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February 1, 2016