Cognitive Reserve in Multiple Sclerosis Modulates Hippocampal Functional Connectivity and Protects from Memory Deficits (P6.124)

OBJECTIVE: We assessed the interaction between cognitive reserve, memory impairment and hippocampal resting state (RS) functional connectivity (FC) in multiple sclerosis (MS). BACKGROUND: The cognitive reserve hypothesis states that enriching experiences protect against dementia and cognitive decline. DESIGN/METHODS: RS fMRI, dual-echo and 3D T1-weighted scans were obtained from 87 MS patients and 49 matched healthy controls (HC). A cognitive reserve index (CRI) was calculated including education, premorbid leisure activity and IQ. Patients were classified in memory impaired (MI) and memory preserved (MP) based on their performance at memory tests of the Rao’s battery. Hippocampal masks were created with FIRST, coregistered to the fMRI scans (SPM8) and used as seed regions for RS FC analysis. Between-group differences of hippocampal RS FC and correlations between RS FC vs clinical, conventional MRI and neuropsychological/CRI variables were assessed using random-effect analyses. RESULTS: Twenty-two patients had MI. Hippocampal atrophy did not differ between MI and MP patients. Since the results obtained from the analysis of the R and L hippocampus were identical, we are reporting those obtained from the R one. Compared to controls and MP patients, MI patients had reduced hippocampal RS FC with the bilateral caudate nucleus, L superior parietal lobule and bilateral superior frontal gyrus; whereas compared to the other two groups MP patients had increased RS FC with the R cerebellum and R orbital gyrus. Higher CRI and higher scores in its three components were related to higher RS FC with the L orbital gyrus. The association between hippocampal RS FC and memory in MS patients was not influenced by global cognitive status, EDSS and whole brain volume, whereas several correlations were detected with hippocampal volume and T2 lesion volume. CONCLUSIONS: Cognitive reserve is likely to contribute to protect from memory decline in MS patients by modulating functional integrity of the hippocampus. Study Supported by: Italian Ministry of Health (GR-2008-1138784).