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Nikolaos Scarmeas, MD; Eric Zarahn, PhD; Karen E. Anderson, MD; Lawrence S. Honig, MD, PhD; Aileen Park, BA; John Hilton, PhD; Joseph Flynn, BS; Harold A. Sackeim, PhD; Yaakov Stern, PhD

Arch Neurol. 2004;61:73-78.

Background  Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathological abnormalities so that he or she remains free of symptoms. Epidemiological data and evidence from positron emission tomography suggest that it may be mediated through education or IQ.

Objective  To investigate CR-mediated differential brain activation in Alzheimer disease (AD) subjects compared with healthy elderly persons.

Participants  Using radioactive water positron emission tomography, we scanned 12 AD patients and 17 healthy elderly persons while performing a serial recognition memory task for nonverbalizable shapes under 2 conditions: low demand, in which one shape was presented in each study trial, and titrated demand, in which the study list length was adjusted so that each subject recognized shapes at approximately 75% accuracy. Positron emission tomographic scan acquisition included the encoding and recognition phases. A CR factor score that summarized years of education, National Adult Reading Test estimated IQ, and Wechsler Adult Intelligence Scale–Revised vocabulary subtest score (explaining 71% of the total variance) was used as an index of CR. Voxel-wise, multiple regression analyses were performed with the "activation" difference (titrated demand–low demand) as the dependent variables and the CR factor score as the independent one. Brain regions where regression slopes differed between the 2 groups were identified.

Results  The slopes were significantly more positive for the AD patients in the left precentral gyrus and in the left hippocampus and significantly more negative in the right fusiform, right middle occipital, left superior occipital, and left middle temporal gyri.

Conclusion  Brain regions where systematic relationships (slopes) between subjects' education-IQ and brain activation differ as a function of disease status may mediate the differential ability to cope with (ie, delay or modify) clinical manifestations of AD.

From the Cognitive Neuroscience Division, Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Scarmeas, Zarahn, Honig, Hilton, and Stern, Ms Park, and Mr Flynn) and the Departments of Neurology (Drs Scarmeas, Honig, and Stern) and Psychiatry (Drs Sackeim and Stern), College of Physicians and Surgeons of Columbia University, New York, NY; and the Department of Psychiatry, University of Maryland, Baltimore (Dr Anderson).

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