Search

Aims: Increasing age is the strongest risk factor for Alzheimer's disease (AD). Yet, departure from normal age-related decline for established markers of AD including memory, cognitive decline and brain function deficits, has not been quantified. Methods: We examined the cross-sectional estimates of the "rate of decline" in cognitive performance and psychophysiological measures of brain function over age in AD, preclinical (subjective memory complaint-SMC, Mild Cognitive Impairment-MCI) and healthy groups. Correlations between memory performance and indices of brain function were also conducted. Results: The rate of cognitive decline increased between groups: AD showed advanced decline, and SMC/MCI groups represented intermediate stages of decline relative to normal aging expectations. In AD, advanced EEG alterations (excessive slow-wave/reduced fast-wave EEG, decreased working memory P450 component) were observed over age, which were coupled with memory decline. By contrast, MCI group showed less severe cognitive changes but specific decreases in the working memory N300 component and slow-wave (delta) EEG, associated with decline in memory. Discussion and Integrative Significance: While the cognitive data suggests a continuum of deterioration associated with increasing symptom severity across groups, integration with brain function measures points to possible distinct compensatory strategies in MCI and AD groups. An integrative approach offers the potential for objective markers of the critical turning point, with age as a potential factor, from mild memory problems to disease.

Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis.