DIFFERENTIAL FUNCTIONAL CONNECTIVITY OF POSTERIOR CINGULATE CORTEX IN THE DECLINE OF COGNITIVE RESERVE BETWEEN AMNESTIC MILD COGNITIVE IMPAIRMENT AND MILD ALZHEIMER’S DISEASE

Abstract

Previous studies have shown that compensatory mechanisms work in the trajectory of Alzheimer's disease (AD). However, brain regions recruited for compensation have been reported to vary according to the trajectory of AD. A cognitive reserve is known as the main source of compensatory mechanisms. Therefore, in this study, we investigated the correlation between the decline of cognitive reserve and the functional connectivity of posterior cingulate cortex (PCC) in the trajectory of AD. A total of 28 subjects, including 11 amnestic mild cognitive impairment (aMCI) subjects and 17 mild AD subjects completed the fMRI. The decline of cognitive reserve is measured by subtracting the premorbid IQ from the current IQ and dividing the result by the premorbid IQ. PCC connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuation in the PCC and those in all other brain regions. In addition, partial correlation analysis was done between the decline of cognitive reserve and PCC connectivity adjusting for age, gender, category of APOE gene, premorbid IQ. We explored the association between the fALFF (fractional amplitude of low frequency fluctuation) in significantly connected regions and cognitive impairments. Amnestic MCI subjects showed significant positive and negative correlation between PCC functional connectivity and the decline of IQ. However, mild AD subjects showed only significant positive correlation between PCC functional connectivity and the decline of IQ. In addition, significant correlations were not observed between fALFF values of significantly connected regions and cognitive impairment in AD subjects but in aMCI subjects. These findings suggest a differential functional connectivity of posterior cingulate cortex between aMCI and mild AD subjects may contribute differential compensatory mechanisms in the decline of cognitive reserve. Brain regions showing significant correlation between PCC functional connectivity and the decline of IQ, (A) aMCI group; (B) mild AD group. Visual inspection reveals the differential correlation pattern between aMCI group and mild AD group. The maps are the results of correlation analysis with corrected p<0.001 and cluster size>(A) 31 voxels; (B) 75 voxels, respectively. Red and blue denotes positive and negative functional connectivity. The color bar indicated the z-values. For the details of the involved regions, see Table 1. PCC, Posterior cingulate cortex. Correlation between the fractional amplitude of low frequency fluctuation(fALFF) in significantly connected regions and cognitive impairments. (A) Regions of positive correlation in aMCI. fALFF values in regions of mild AD group showed no significant correlation with cognitive impairments. Significantly connected regions are listed in Table 1. Cognitive impairments were assessed by the Korean version of Consortium to Establish a Registry for Alzheimer's disease. VF, verbal fluency; MMSE, Mini Mental Status Examination CP, constructional praxis. Correlation between the fractional amplitude of low frequency fluctuation(fALFF) in significantly connected regions and cognitive impairments. (B) Regions of negative correlation in aMCI. fALFF values in regions of mild AD group showed no significant correlation with cognitive impairments. Significantly connected regions are listed in Table 1. Cognitive impairments were assessed by the Korean version of Consortium to Establish a Registry for Alzheimer's disease. MMSE, Mini Mental Status Examination; BNT, 15-item Boston Naming Test; WLM, Word List Memory.