P3-169: Reduced default network functional connectivity and verbal learning in cognitively unimpaired late middle-aged and older adults: Exploratory findings from the arizona ApoE cohort study

Epidemiological studies have implicated that metabolic syndrome (defined as the presence of 3 out of 5 factors: abdominal obesity, elevated triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose) is associated with the risk of age-related cognitive decline and the clinical stages of Alzheimer's Disease (AD). In this study, we explored the possibility that the metabolic syndrome is associated with altered default mode network (DMN) functional connectivity, memory and learning in cognitively unimpaired late middle-aged and older adults with two, one and no copies of the apolipoprotein E (APOE4) allele, the major genetic risk factor for late-onset AD. Resting state functional connectivity magnetic resonance images (fcMRIs) and auditory verbal learning test (AVLT) long-term recall, immediate recall, and learning test scores were analyzed in 98 cognitively unimpaired 65±4 year old adults with a reported first degree family history of dementia, including 16 APOE4 homozygotes, 26 heterozygotes, and 56 non-carriers with similar ages, gender distributions, and educational levels. A DMN map was created from each person's fcMRI using the right angular gyrus as the seed region of interest. Metabolic syndrome was associated with reduced resting state functional connectivity of several DMN regions, including right precuneus, lateral parietal cortex, right and left hippocampal, lateral temporal, frontal and occipital cortex locations, and with increased connectivity in other DMN regions, including temporal, frontal, and occipital locations (P<0.001, uncorrected for multiple regional comparisons). It was also associated with reduced AVLT learning scores (P=0.03, uncorrected for the 3 AVLT comparisons). Functional connectivity, memory and learning findings were not significantly associated with APOE4 gene dose. While our findings should be considered exploratory, they support the possibility that metabolic syndrome is associated with age-related declines in learning and the risk for AD, and they illustrate how functional connectivity MRI can be used as a preclinical endophenotype of AD.