Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables.