IC‐P‐038: DIFFERENTIAL LONGITUDINAL POSTERIOR CINGULATE CORTEX CONNECTIVITY TRAJECTORIES IN NORMAL AGING, MCI AND AD

The default mode network (DMN) changes with Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal aging, but these changes are not well characterized. The posterior cingulate cortex (PCC) is a critical hub in the DMN. Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we modeled longitudinal change in PCC connectivity in three subject groups: healthy controls (HC), MCI, and AD, and tested whether connectivity changes were linear or quadratic with time. The HC group had no evidence of Aβ accumulation (N=56, 25 male, 75.7±6.23 years). The MCI group pooled all MCI and significant memory concern subjects with no signs of dementia (N=127, 59 male, 72.6±7.14 years). The AD group fulfilled the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA, now known as the Alzheimer's Association) criteria for probable AD (N=34, 16 male, 74.2±7.47 years). We processed resting state fMRI images using a workflow that represents best practices for removal of noise, censoring motion outliers. We measured individual connectivity to a 10mm sphere in the PCC (2,-52,28) and transformed the Pearson correlations using a Fisher Z-transformation. We used neuropointillist (http://ibic.github.io/neuropointillist/) to fit a mixed effects growth model in R to each voxel, comparing linear and quadratic forms of longitudinal change. Data were cluster corrected for multiple comparisons at p=.05, α=.05. Figure 1 shows our results. A linear model was superior to a quadratic model for all groups across the brain. All three groups showed decreased connectivity with age of the PCC to the medial frontal wall. However, we found increased connectivity to the dorsal attention network only in the MCI group. Longitudinal Change in Functional Connectivity to the PCC in Normal Aging, MCI, and AD Groups. In the normal aging group (Figure 1A), connectivity decreased (blue) in the sensorimotor cortex and increased (red-yellow) in the putamen and lateral occipital cortex. In the MCI group (Figure 1B), connectivity increased in the dorsal attention network and decreased in the medial frontal wall. In the AD group (Figure 1C), connectivity increased in the premotor cortex/ cingulate gyrus and decreased in the medial frontal cortex. We identified distinct regions of the brain that increased and decreased in connectivity to the PCC with age in the three subgroups. These differences likely represent the different pathophysiological processes occurring in normal aging, MCI, and AD. Longitudinal analysis of resting state fMRI has great power and promise to highlight pathophysiological impact on brain systems.