INTERACTIVE INFLUENCE OF DEPRESSION AND APOE-E4 ALLELE ON THE DEFAULT MODE NETWORK IN SUBJECTIVE COGNITIVE IMPAIRMENT

Abstract

Functional connectivity in resting state network may represent a subtle deficit of brain function in the very early or presymptomatic stage of Alzheimer's disease (AD). Subjective cognitive impairment (SCI) as a preclinical stage of AD may demonstrate the functional compensation for brain declines. Depression may be manifested as an early symptom of AD. This study aimed to investigate the effect of depression on the resting state functional connectivity in SCI with and without APOE e4 allele. We consecutively recruited patients aged 55 and older who came to the memory clinic with subjective cognitive complaints but performed normally on neuropsychological tests (z > -1 in verbal delayed recall and z > -1.5 in the other cognitive tests). The final sample (n=180, mean age of 65.6 (SD 6.9) years, 127 females and 53 males) consisted of 134 APOE e4 noncarriers (e3/e3) and 46 carriers (e3/e4 or e4/e4). 21.1% of patients had depression. Presence of depression was defined by the total score > 17 in the Korean version of Geriatric depression scale. Resting state fMRI data were acquired using 3T MRI. Degrees of functional connectivity in four resting state networks (default mode network (DMN), executive control network, dorsal attention network, salience network) were calculated using the mean positive correlation coefficients between brain voxels and the seed in each network. Among four resting state networks, only DMN was associated with depression. SCI patients with depression had the decreased DMN connectivity compared to those without depression. Although the overall interaction effect was not statistically significant, the degree of the reduction in DMN connectivity tended to differ between APOE e4 noncarriers and carriers. Whereas in APOE e4 noncarriers depressive patients had significantly decreased connectivity compared to nondepressive patients, the difference was not significant in carriers. Depression in SCI altered the functional connectivity of DMN. However, this effect was evident only in APOE e4 noncarriers. While APOE e4 carriers with depression also had decreased functional connectivity, the degree of decrease was small. This may indicate APOE e4 carriers might develop the partial compensation process for their subtle changes in the brain.