fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: risk factors for Alzheimer's disease.

In the present study, we used fMRI to examine the influence of age on two other known risk factors for Alzheimer's disease (AD), APOE genotype and parental history of AD (FH status), during episodic encoding (ENC) and metacognitive self-appraisal (SA) paradigms. These paradigms have previously been shown to evoke activity from brain regions that are implicated in AD. First we examined the effect of age across the adult lifespan (age 18-84 years) on cerebral activity in a large sample (n=231) of cognitively healthy individuals. Next we examined a subset (n=155) on whom APOE status and FH status were known. For ENC, we found that increasing age was associated with reduced activity in the ventral temporal lobes and hippocampus. Our analysis of risk factors suggested that FH and age exerted independent effects, but APOE interacted with age such that APOE e4 carriers exhibit age-related increases in activity in the hippocampus. For the metacognitive SA task, increasing age was found to be associated with reduced activity in the medial prefrontal cortex, and increased activity in the mesial temporal lobe, posterior orbital cortex and striatum. Neither AD risk factor significantly modified age-related changes in brain activity during SA. These results suggest that FH and aging are exerting independent effects in both tasks while APOE affected the relationship with age in the hippocampus in one of the two tasks given.