Rates of decline distinguish Alzheimer's disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function

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.