IC-P-015: Age-related decline in hippocampal and ventral temporal lobe activation during episodic encoding

Abstract

Increasing age is a major risk factor for Alzheimer's disease (AD). Previous studies have reported age–related volumetric decline in medial temporal lobe (MTL) structures that display pathological changes in AD. Recent evidence suggests that young individuals display significantly greater functional activation in the MTL relative to elderly individuals during episodic encoding. To date, few studies have included middle–aged individuals (i.e., 35–60 years) to determine whether these individuals also display reduced hippocampal activation during episodic encoding relative to younger individuals. The present study used functional MRI to test the hypothesis that there would be an age–related decline in MTL activation during episodic encoding in 142 individuals between 19 and 83 years of age using a task sensitive to reduced hippocampal activation in individuals with mild cognitive impairment (MCI). Participants were divided into 6 different groups: 19–24 years (n = 27), 25–36 years (n = 21), 40–49 years (n = 22), 50 – 59 years (n = 37), 60–69 years (n = 19), and 70 years or greater (n = 16). Individuals with psychiatric/neurological disease were excluded, and all participants received a detailed neuropsychological evaluation to exclude subjects with cognitive impairments. We found a linear, parametric decline in right hippocampal and bilateral ventral temporal cortex activation during episodic encoding as a function of increasing age (FDR–corrected p < 0.05). In contrast, a similar pattern was not observed in the left MTL as a function of increasing age. Furthermore, no brain regions displayed a significant parametric increase in activation as a function of increasing age. These results suggest that increasing age is associated with a decline in medial and ventral temporal lobe activation during memory encoding, despite intact cognitive function on standardized neuropsychological measures. Since increasing age is a major risk factor for AD, hippocampal activation paradigms might be useful in studying individuals with risk factors for AD (e.g., MCI, APOE ε4 allele, or parental–history of AD). More studies that better characterize changes in hippocampal activation across the entire age spectrum are needed before fMRI is to be used in the early diagnosis of MCI or AD.