Evidence for Structural and Functional Alterations of Frontal-Executive and Corticolimbic Circuits in Late-Life Depression and Relationship to Mild Cognitive Impairment and Dementia: A Systematic Review

Abstract

Depression is a risk factor for developing Alzheimer's disease and Related Dementia (ADRD). We conducted a systematic review between 2008 and October 2018, to evaluate the evidence for a conceptual mechanistic model linking depression and ADRD, focusing on frontal-executive and corticolimbic circuits. We focused on two neuroimaging modalities: diffusion-weighted imaging measuring white matter tract disruptions and resting-state functional MRI measuring alterations in network dynamics in late-life depression (LLD), mild cognitive impairment (MCI), and LLD+MCI vs. healthy control (HC) individuals. Our data synthesis revealed that in some but not all studies, impairment of both frontal-executive and corticolimbic circuits, as well as impairment of global brain topology was present in LLD, MCI, and LLD+MCI vs. HC groups. Further, posterior midline regions (posterior cingulate cortex and precuneus) appeared to have the most structural and functional alterations in all patient groups. Future cohort and longitudinal studies are required to address the heterogeneity of findings, and to clarify which subgroups of people with LLD are at highest risk for developing MCI and ADRD.

Autoregressive cross‐lagged modelling of the relationship between social activity, depressive symptoms, and cognitive function in Korean elderly

“…One systematic review argued that there may be etiopathological mechanisms (e.g. a vascular pathway) that link elderly depression to cognitive impairment 15 . In addition, previous studies have indicated that deficits in attention, memory, and executive function appear during major depressive episodes 16,17 …”

Depression in Alzheimer's Disease: A Delphi Consensus on Etiology, Risk Factors, and Clinical Management

“…In their voxel-based morphometry analysis, Karavasilis et al suggested that Alzheimer and depression comorbidities may be characterized by a specific pattern of gray matter loss that coincides with anatomical regions of the sensorimotor system and the right thalamus (71). In the same line, and as discussed earlier on, Rashidi-Ranjbar et al's work focused on two neuroimaging techniques, namely diffusionweighted imaging measuring white matter tract disruptions and resting-state functional MRI, to provide important clues on both functional and structural abnormalities shared by patients with late-life depression and/or MCI (38). Other studies show that [18F]-fluorodeoxyglucose (FDG) and amyloid-PET techniques allow in vivo assessment of regional glucose metabolism and betaamyloid plaque deposition, respectively, and their association with cognitive, behavioral, and physical performance in MCI and AD (72,73).…”

“…As mentioned earlier, both disturbances appear to be linked through common neurobiological mechanisms (32,(36)(37)(38)(39), but it is still unclear whether depression is an etiological factor, a prodromal symptom, a coincidental finding or a secondary effect of dementia (12,27,28). Thus, manifestations of depression may not precede cognitive decline but arise in the presence of clinically overt dementia (46,47).…”

“…Whether depressive symptom trajectory influences the progression of AD and other dementias has not been fully elucidated, and data from different authors have led to contradictory conclusions (32)(33)(34)(35). However, there is mounting evidence to support common etiological mechanisms between depression and neurodegenerative pathologies (32,(36)(37)(38), therefore it seems plausible to suspect on an additive effect…”

“…Genetic variations and neurobiological factors such as cerebrovascular disease, proinflammatory cytokines, cortisol and increased amyloid production, and accumulation may confer comorbidity risk (28,37,39). From a structural and functional point of view, a recent systematic review by Rashidi-Ranjbar et al concluded that overlapping alterations in both frontal-executive and corticolimbic circuits, as well as alterations of global brain topology can be observed in many studies analyzing late-life depression and mild cognitive impairment patient samples (38). There are also doubts as to whether antidepressants can reverse the deleterious effects of depression on dementia due to the scarcity of specifically driven studies.…”