COGNITIVE TEST DISPERSION AND FUNCTIONAL CONNECTIVITY IN OLDER ADULTS WITH MAJOR DEPRESSION

Abstract

Introduction Performance variability across a battery of cognitive tests, otherwise known as dispersion, has been shown to be predictive of an increased risk of developing Mild Cognitive Impairment (MCI) and Alzheimer's disease. We previously found that test dispersion in older adults with major depression was: 1) correlated with white matter disease on structural MRI and 2) predictive of worsening on memory test performance one year later (even when controlling for baseline memory test performance and other relevant clinical and demographic factors). There is little evidence regarding fMRI and dispersion and the underlying functional connectivity impact that increased dispersion may have on neural networks. The goal of the current study was to explore the relationship between cognitive dispersion and resting-state activity measured by amplitude of low-frequency fluctuation (ALFF) and functional connectivity in non-demented older adults diagnosed with major depression. We hypothesized that dispersion would be correlated with resting-state activity as well as functional connectivity in neural networks related to executive functioning and memory. Methods Subjects included 61 older adults with major depression (MD) who had participated in the NBOLD study at UConn Health. Inclusion criteria included age 60+ and a formal diagnosis of major depression. Those with dementia or other significant neuropsychiatric disorders were excluded from the study. Dispersion was defined as the spread of scores on a comprehensive neuropsychological battery, calculated as the coefficient of variation, or standard deviation of z-scores divided by the group mean z-scores. 7-min resting state fMRI data was acquired from 3T Siemens scanner. DPABI software was used to conduct preprocessing and ALFF calculation. Significant clusters that showed ALFF correlation between ALFF and dispersion (p Results Subject demographics were as follows; age (Mean=71.8yrs, SD=±7.3yrs), 27.9% male, MADRS (Mean=18.2, SD=±6.2). ALFF in the posterior cingulate cortex (PCC) and left hippocampal cortex (LHC) were negatively correlated with dispersion while ALFF of the dorsolateral prefrontal cortex (dlPFC) was positively correlated with dispersion. Using these regions as ROIs, we found functional connectivity between the dlPFC seed and left inferior parietal cortex ((angular gyrus), peak -58, -56, 24; cluster size 110; p=.00196), the executive network, was positively correlated with cognitive dispersion. Conclusions Dispersion is negatively correlated with ALFF in brain areas related to memory (hippocampus and PCC), but positively related to ALFF in the dlPFC, a key region of executive functioning and attention. Functional connectivity of the executive network was also positively correlated with dispersion, suggesting possible deficits in resting activity of the memory system, and compensatory increase of resting activity and connectivity of the executive system in MD subjects with high dispersion. Future studies may continue to look at anatomical relationships with cognitive dispersion and performance on neuropsychological tests in those with MD, as well as further explore the impact that dispersion has on neural networks. This research was funded by: Data and research that was reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, and UL1GM118970; by NIMH grant R01 MH108578; and by the Leo and Anne Albert Charitable Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.