P2–372: Decline in cognitive performance and metabolism in a medial brain network during aging in healthy controls

Background: The brain metabolic and cognitive changes occurring in the healthy elderly require further study (e.g., A. Martin et al., 1991; J. Moeller et al., 1996; S. Schultz et al., 1999). Defining these alterations is necessary to distinguish healthy individuals from those with early AD/MCI. In particular, it is unknown whether any declines in cognition relate to specific foci of age-related decline in brain metabolism. Objective(s): To identify brain metabolic changes that correlate with aging and with measures of cognitive performance. Methods: A cohort of healthy subjects from young adulthood to the elderly were recruited for a normative database. The subjects had laboratory and physical examination; cognitive screening with the Minnesota Cognitive Acuity Screen (MNCAS; Knopman et al., 2000); clinical MRI; APOE genotyping; and FDG PET during the eyes closed, resting state. PET data were processed with 3D SSP (S. Minoshima et al., 1995) and in-house software. PET data were not otherwise corrected for structural atrophy so that observed changes may reflect a combination of decreased metabolism or structural atrophy. Results: Several regions of the brain showed significant negative correlations of metabolism with age. The major areas included doral medial prefrontal and anterior cingulate; subgenual cingulate/basal forebrain; and dorsomedial thalamus (Fig. 1; color scale displays correlations between -1 and 0). There were also less extensive regions in various lateral hemisphere areas. Decline in cognitive measures correlated with foci in medial but not lateral regions. Conclusions: Medial brain regions known to be interconnected anatomically and to participate in executive function show age-related metabolic declines that correlate with decreases in several cognitive measures. These areas provide a background over which MCI/AD occur; they are typically removed by age regression in PET studies of MCI/AD. These findings bear upon the biology of normal aging and offer biological substrates to target age-related cognitive decline.