Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

Abstract

Background: Late Life Depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the Default Mode Network (DMN), the Cognitive Control Network (CCN), and the Salience Network (SN). However these findings often derive from small samples and it is not well understood how network findings relate to clinical and cognitive symptomatology. Methods: We studied 100 older adults (n=79 with LLD, n=21 nondepressed) and collected resting state functional MRI, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and SN) as seeds in seed-to-voxel analysis. We compared connectivity between depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. Results: LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ 2 =22.33, P<0.001). No significant group differences in connectivity were found for the CCN or SN. However, in the LLD group increased CCN connectivity was associated with increased depression severity (Wald χ 2 >20.14, p<0.001), greater anhedonia (Wald χ 2 =7.02,

Accelerated brain aging predicts impaired cognitive performance and greater disability in geriatric but not midlife adult depression

“…Two of the geriatric studies used identical neuropsychological test batteries and so were included in analyses examining cognitive performance. As previously published 20 , 33 , for the geriatric cohort, tests in each domain included: Episodic Memory (CoA = 0.75): Word List Memory Recall (immediate and delayed), Paragraph Recall test, Constructional Praxis test (delayed), Benton Visual Retention Test; Executive Function (CoA = 0.66): COWA test (letters: C, F, L), Trail Making B time (reverse scored), Stroop test color-word interference condition, Mattis Dementia Rating Scale, Initiation-Perseveration subscale; Processing Speed (CoA = 0.74): Symbol-Digit Modality Test, Trail-Making A time (reverse scored), Stroop color naming condition; Working Memory (CoA = 0.71): Digit Span forward, Digit Span backward, and Ascending Digits from the Wechsler Memory Scale. …”

“…All study participants provided written informed consent. Data from the adult cohort has previously been reported 28 , 29 and we have also reported cognitive data from the geriatric cohort 20 .…”

“…The examination of brain aging may have particular utility in older populations and late-life depression, or geriatric MDD. Geriatric MDD is associated with cerebrovascular pathology 17 , higher risk for dementia 18 , and greater medical morbidity 19 that may contribute to impairment in multiple cognitive domains 20 and accelerated brain aging. For example, diabetes mellitus, a risk factor both for cerebrovascular disease, dementia, and depression, is also associated with an increased brain-age gap 21 .…”

Persistent Intrinsic Functional Network Connectivity Alterations in Middle-Aged and Older Women With Remitted Depression

“…First-and second-level analyses were conducted using standard methods in the Conn Toolbox (34). We selected canonical network regions for each intrinsic functional network to use as key network seed regions of interest: 1) a DMN seed [PCC (50)], 2) bilateral ECN seeds [dlPFC (23)], 3) bilateral SN seeds [anterior insula (23)], and bilateral hippocampal seeds (51) ( Table 1).…”

“…The SN is activated in response to various salient stimuli (33) and facilitates switching between the DMN and ECN to shift attention from internal states to external stimuli (34). In MDD, SN regions are generally overresponsive to affective challenges, particularly negatively valenced stimuli (35).…”