P1-295: Longitudinal functional MRI demonstrates loss of hippocampal activation associated with clinical decline in nondemented older subjects

Our previous cross-sectional functional MRI (fMRI) research has demonstrated hippocampal dysfunction in MCI subjects, suggesting there may be a phase of paradoxically increased hippocampal activation in early stages of MCI, while more impaired MCI subjects demonstrate decreased hippocampal activation similar to clinical AD patients. In this study, we utilized longitudinal fMRI studies over 2 years to investigate whether clinical decline is associated with increased activation at baseline and loss of hippocampal function over time. Fifty-one nondemented older subjects (CDR 0=21; CDR 0.5=30; age 74.8 +/-5.4) underwent clinical assessments and fMRI during an associative memory paradigm at baseline and at 2-years. MRI data were acquired on a 3T Siemens Trio and were analyzed in SPM2 with whole brain activation maps and hippocampal regions-of-interest (ROI). At 2-year follow-up, 15 subjects were classified as Stable CDR 0 (no change in CDR Sum of Box); 12 as Stable CDR 0.5 (no change in SB); 11 as Slow-Decliners (CDR 0/0.5 SB change =.5) and 13 as Fast-Decliners (CDR 0/0.5 SB change of 1). Fast-Decliners also demonstrated a significant decline in verbal memory performance (p = 0.024). Repeated measures whole brain and ROI analyses demonstrated no change over 2 years in Stable CDR 0, minimal change in Stable CDR 0.5 and Slow-Decliners, but a significant decrease in hippocampal activation in Fast-Decliners (p<0.001). Across all 51 subjects, change in CDR-SB correlated change in hippocampal activation (R=-.34; p=.014. Interestingly, greater baseline hippocampal activation was associated with greater decline on CDR-SB (R=.37; p=.008) and greater loss of hippocampal signal (R=.70; p<0.001). Preliminary volumetric analyses did not demonstrate a significant contribution of atrophy to the observed fMRI findings.