Brain connectivity in late-life depression and aging revealed by network analysis.
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ABSTRACT:
SUBMITTER: Charlton RA
PROVIDER: S-EPMC4327993 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
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Project description:Prior studies have demonstrated dysfunctions within the core neurocognitive networks (the executive control [ECN], default mode [DMN] and salience [SN] networks) in late-life depression (LLD). Whether inter-network dysfunctional connectivity is present in LLD, and if such disruptions are associated with core symptom dimensions is unknown. A cross-sectional resting-state functional connectivity magnetic resonance imaging investigation was conducted of LLD (n = 39) and age- and gender-equated healthy comparison (HC) (n = 29) participants. Dual regression independent component analysis approach was used to identify components that represented the ECN, DMN and SN. The intrinsic inter-network connectivity was compared between LLD and HC participants and the relationship of inter-network connectivity abnormalities with dimensional measures was examined. Relative to HC participants, LLD subjects showed decreased inter-network connectivity between the bilateral ECN and default mode subcortical (thalamus, basal ganglia and ventral striatum) networks, and the left ECN and SN insula component; and increased inter-network connections between the left ECN and posterior DMN and salience (dorsal anterior cingulate) network components. Distinct inter-network connectivity abnormalities correlated with depression and anxiety severity, and executive dysfunction in LLD participants. LLD subjects also showed pronounced intra-network connectivity differences within the ECN, whereas fewer but significant DMN and SN disruptions were also detected. Investigating the intrinsic inter-network functional connectivity could provide a mechanistic framework to better understand the neural basis that underlies core symptom dimensions in LLD. Inter-network connectivity measures have the potential to be neuroimaging biomarkers of symptom dimensions comprising LLD, and may assist in developing symptom-specific treatment algorithms.
| S-EPMC5336398 | biostudies-literature
Project description:The clinical presentation of late-life depression is highly heterogeneous and likely influenced by the co-presence of somatic diseases. Using a network approach, this study aims to explore how depressive symptoms are interconnected with each other, as well as with different measures of somatic disease burden in older adults. We examined cross-sectional data on 2860 individuals aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, Stockholm. The severity of sixteen depressive symptoms was clinically assessed with the Comprehensive Psychopathological Rating Scale. We combined data from individual clinical assessment and health-registers to construct eight system-specific disease clusters (cardiovascular, neurological, gastrointestinal, metabolic, musculoskeletal, respiratory, sensory, and unclassified), along with a measure of overall somatic burden. The interconnection among depressive symptoms, and with disease clusters was explored through networks based on Spearman partial correlations. Bridge centrality index and network loadings were employed to identify depressive symptoms directly connecting disease clusters and depression. Sadness, pessimism, anxiety, and suicidal thoughts were the most interconnected symptoms of the depression network, while somatic symptoms of depression were less interconnected. In the network integrating depressive symptoms with disease clusters, suicidal thoughts, reduced appetite, and cognitive difficulties constituted the most consistent bridge connections. The same bridge symptoms emerged when considering an overall measure of somatic disease burden. Suicidal thoughts, reduced appetite, and cognitive difficulties may play a key role in the interconnection between late-life depression and somatic diseases. If confirmed in longitudinal studies, these bridging symptoms could constitute potential targets in the prevention of late-life depression.
| S-EPMC8557204 | biostudies-literature
Project description:BackgroundLate-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.MethodsParticipants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.ResultsIn primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.ConclusionsResponse to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.RegistrationClinicalTrials.gov NCT02332291.
| S-EPMC10250562 | biostudies-literature
Project description:Recent studies have shown that aging has a large impact on connectivity within and between functional networks. An open question is whether elderly still have the flexibility to adapt functional network connectivity (FNC) to the demands of the task at hand. To study this, we collected fMRI data in younger and older participants during resting state, a selective attention (SA) task and an n-back working memory task with varying levels of difficulty. Spatial independent component (IC) analysis was used to identify functional networks over all participants and all conditions. Dual regression was used to obtain participant and task specific time-courses per IC. Subsequently, functional connectivity was computed between all ICs in each of the tasks. Based on these functional connectivity matrices, a scaled version of the eigenvector centrality (SEC) was used to measure the total influence of each IC in the complete graph of ICs. The results demonstrated that elderly remain able to adapt FNC to task demands. However, there was an age-related shift in the impetus for FNC change. Older participants showed the maximal change in SEC patterns between resting state and the SA task. Young participants, showed the largest shift in SEC patterns between the less demanding SA task and the more demanding 2-back task. Our results suggest that increased FNC changes from resting state to low demanding tasks in elderly reflect recruitment of additional resources, compared with young adults. The lack of change between the low and high demanding tasks suggests that elderly reach a resource ceiling.
| S-EPMC6869581 | biostudies-literature
Project description:Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.
| S-EPMC3865521 | biostudies-literature
Project description:The present study investigated functional connectivity and white matter integrity of the fronto-parietal network (FPN) to reveal the neural mechanisms that underlie late-life depression (LLD). Fifty patients with LLD and 40 non-depressed controls were included in the study. A multi-parametric approach was used by applying independent component analysis (ICA) to estimate functional connectivity of the FPN and by applying tract-based spatial statistics to examine white-matter integrity in tracts to the FPN. Patients with LLD exhibited functional abnormalities in the right inferior frontal gyrus, middle frontal gyrus, and inferior parietal gyrus and lower white matter fractional anisotropy in the right inferior fronto-occipital fasciculus, anterior thalamic radiation, and uncinate fasciculus. Alterations of functional connectivity and white matter fractional anisotropy in these regions were negatively correlated with the severity of symptomatic anxiety in LLD patients. The right inferior frontal gyrus might be a crucial hub in transferring information between these abnormal regions. Significant correlations were found between anxiety symptoms and brain alterations, suggesting that impairments in the FPN network might be involved in symptomatic anxiety in elderly individuals with depression.
| S-EPMC7491145 | biostudies-literature
Project description:BackgroundThere is limited research examining the impact of risk and protective factors on late-life depression using large population-based datasets, particularly those examining differences among older migrants and non-migrants in Europe countries. Thus, the first aim was to analyze differences between migrants and non-migrants regarding socioeconomic status, depression, multimorbidity, healthy aging, and lifestyle behaviors. The second aim was to examine the impact of healthy aging on late-life depression in older migrants compared to their counterparts without a history of international migration in extensive and harmonized data from different population-based cohort studies.Materials and methodsWe analyzed cross-sectional, predominantly nationally representative, community-based data from European participants in the Aging Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) cohort. The descriptive analyses included sociodemographic variables, somatic comorbidities, multimorbidity, healthy aging, and lifestyle behaviors according to migration status. The effects of these variables on late-life depression were examined in a multivariate logistic regression model, including migration status and years since migration as predictors.ResultsData of 122,571 individuals aged ≥ 50 years were analyzed, of which 11,799 (9.60%) were migrants. The descriptive analyses indicated that compared to non-migrants, migrants showed a higher prevalence of diabetes (25.6%), hypertension (38.0%), coronary artery disease (49.4%), stroke (4.9%), and depression (31.1%). Healthy aging was also better in non-migrants (51.7; SD = 9.7) than in migrants (39.6; SD = 18.2). The results of the logistic regression showed that migration status [OR = 1.231 (CIs: 0.914-1.547)] and increased number of years since migration in the host country [OR = 0.003 (CIs: 0.001-0.005)] were associated with greater levels of depressive symptoms. Concerning health variables, multimorbidity was associated with higher levels of depressive symptoms [OR = 0.244 (CIs: 0.211-0.278)], whereas better healthy aging was associated with fewer depressive symptoms [OR = -0.100 (CIs: -0.102 to -0.098)]. The interaction between migration and healthy aging status was also significant [OR. = -0.019 (CIs: -0.025 to -0.014)].ConclusionMigrants reported higher risks for worse health outcomes compared to non-migrants. Significantly, worse healthy aging was associated with a greater risk of depressive symptoms in migrants than in non-migrants. Shedding light on migration and aging processes is essential for promoting a cross-cultural understanding of late-life depression in Europe.
| S-EPMC9680089 | biostudies-literature
Project description:BackgroundMajor depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved.MethodsThis is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function.DiscussionThe main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT.Trial registrationClinicalTrials.gov Identifier: NCT03849417 , 21/2/2019.
| S-EPMC7845114 | biostudies-literature
Project description:Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.
| S-EPMC5858586 | biostudies-literature
Project description:ObjectiveThis study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants.DesignCross-sectional study.ParticipantsWe included 111 older adults (80 with LLD and 31 comparison participants) in this study.MeasurementA panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein.ResultsParticipants with LLD showed a significantly increased SASP index compared with comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, sex, and cognitive performance (F(1,98) = 7.3, p = 0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r = 0.2, p = 0.03) and CIRS score (r = 0.27, p = 0.005), and negatively correlated with information processing speed (r = -0.34, p = 0.001), executive function (r = -0.27, p = 0.004) and global cognitive performance (r = -0.28, p = 0.007).ConclusionsTo the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD.
| S-EPMC5164865 | biostudies-literature