Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease. (JINS, 2012, 18, 1–11)

When compared with controls, both mild cognitive impairment (MCI) and dementia are each associated with impaired memory for future intentions, or prospective memory (PM). However, prior studies have failed to agree on whether there are group differences in PM function between those with MCI and dementia. Furthermore, the degree and nature of the impairment remains to be clarified, as does the degree to which this impairment is secondary to deficits in other aspects of cognition. In the present study, MCI (n = 48), dementia (n = 39), and control participants (n = 53) were compared on Virtual Week, a measure that closely represents the types of PM tasks that occur in everyday life. Both clinical groups exhibited impairment irrespective of the specific task demands, but the magnitude of this deficit was greater for those with dementia. After covarying for other key cognitive parameters, although the absolute magnitude of the deficit was reduced, significant impairment remained. These results indicate that individuals with MCI, and to a greater extent dementia, experience generalized difficulties with PM. It is suggested that, while other cognitive deficits contribute to these difficulties, there is something unique to prospective remembering that may be additionally disrupted in these groups. (JINS, 2010, 16, 318–325.)