STRUCTURAL ABNORMALITIES OF LIMBIC SYSTEM SERVE AS POTENTIAL BIOMARKERS FOR THE ONSET AND PROGRESSION OF MILD COGNITIVE IMPAIRMENT

With rapidly aging of population worldwide, Alzheimer's disease (AD) has been one of the most destructive diseases nowadays. As the consensus that clinical AD could hardly be inversed or cured, great importance has been attached to the early detection of AD. Mild cognitive impairment (MCI) came up as the early stage of AD, when cognitive impairment was able to be detected by neuropsychological tests. However, accumulating evidence suggested that MCI patients have already shown obvious brain structural damages, coming up with speculation that MCI could be the later phase of preclinical AD. To emphasize this, we analyzed serial anatomical imaging data from cognitively normal old community residents, who were followed for years and diagnosed as MCI or not. 76 participants from Beijing Aging Brain Rejuvenation Initiative (BABRI) projects, who aged 55 to 76 years old, had full neuropsychological profile and underwent at least twice high-resolution T1-weighted MRI scans, were included. During the follow-up, 13 progressed MCI (NC-p) and 59 remained cognitively intact (NC-s). After preprocessing data with longitudinal registration toolbox in SPM12, we conducted voxel-wise linear mixed effect (LME) analyses to address structural alterations in grey matter (GM) during MCI development and normal aging. Scan intervals were 2.2±0.4 and 2.3±0.6 years for NC-p and NC-s, respectively. After regressing out the baseline age (66.4±7.7 yrs. vs. 63.7±5.7 yrs.), gender ratio (3Male/10Female vs. 28Male/30Female) and years of education (11.9±3.6 yrs. vs. 10.9±2.6yrs.), inspections on baseline GM volume turned out that bilateral insula were significantly smaller in NC-p, and later examinations on the last scans identified similar, but wider regions around bilateral insula with lower volume (corrected p<0.05). Further LME analyses suggested that while NC-s showed more extensive atrophy during follow-up, mainly involving prefrontal and tempo-parietal cortices, atrophy of NC-p was limited to bilateral thalamus (corrected p<0.05); more importantly, besides overlapping of atrophy in right thalamus, accelerated GM loss was found in clusters involving left thalamus in NC-p (uncorrected p<0.005, Cluster Size>200). The significant smaller insula, as well as accelerated thalamus atrophy, in elders who progressed MCI later, implied that subcortical limbic structures could be potential biomarkers for detecting onset of cognitive impairment . Group Differences at baseline and last scans. regions showing GM atrophyi n NC-p (in green), NC-s (in blue), and group-interaction (in red).