Late-life Depression Research Articles

Depression, Vascular Burden, and Dementia Prevalence in Late Middle-Aged and Older Black Adults.

Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume. Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia. Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals. Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors.

Long-term effects of childhood difficulties on depressive symptoms among older adults: Role of adulthood income and income satisfaction.

This study examines how childhood difficulties are associated with late-life depression. Using the concept of agency within the structure of the life course perspective, this study investigates how subjective income satisfaction in adulthood plays a role in the relationship between adulthood objective income and late-life depressive symptoms among older adults who have experienced childhood difficulties. Using data from two waves (2006, 2021) of the Korean Welfare Panel Study (N = 1822), we identified respondents with and without childhood difficulties, and performed a series of hierarchical zero-inflated Poisson regression models. Childhood difficulties (β, 0.07; 95% confidence interval [CI], 0.04-0.11), adulthood low income (β, 0.17; 95% CI, 0.13-0.21), and low income satisfaction (β, 0.16; 95% CI, 0.12-0.21) are associated with an increased level of depressive symptoms in late life. In the context of the association between objective income level and late-life depressive symptoms, the buffering effect of income satisfaction in adulthood was found among the respondents who had experienced childhood difficulties (β, 0.22; 95% CI, 0.09-0.34). Childhood difficulties are a critical risk factor impacting late-life psychological well-being. How an individual subjectively evaluates his or her economic status in adulthood plays a major role in mitigating the negative impact of childhood difficulties on late-life health inequality. Interventions to reduce the risk of childhood difficulties and their negative long-lasting impact may alleviate individuals' exposure to depression in late life. Geriatr Gerontol Int 2024; 24: 246-252.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Sex differences in plasma proteomic markers in late-life depression

Previous studies have shown significant sex-specific differences in major depressive disorder (MDD) in multiple biological parameters. Most studies focused on young and middle-aged adults, and there is a paucity of information about sex-specific biological differences in older adults with depression (aka, late-life depression (LLD)). To address this gap, this study aimed to evaluate sex-specific biological abnormalities in a large group of individuals with LLD using an untargeted proteomic analysis. We quantified 344 plasma proteins using a multiplex assay in 430 individuals with LLD and 140 healthy comparisons (HC) (age range between 60 and 85 years old for both groups). Sixty-six signaling proteins were differentially expressed in LLD (both sexes). Thirty-three proteins were uniquely associated with LLD in females, while six proteins were uniquely associated with LLD in males. The main biological processes affected by these proteins in females were related to immunoinflammatory control. In contrast, despite the smaller number of associated proteins, males showed dysregulations in a broader range of biological pathways, including immune regulation pathways, cell cycle control, and metabolic control. Sex has a significant impact on biomarker changes in LLD. Despite some overlap in differentially expressed biomarkers, males and females show different patterns of biomarkers changes, and males with LLD exhibit abnormalities in a larger set of biological processes compared to females. Our findings can provide novel targets for sex-specific interventions in LLD.

The Long Arm of Childhood Bullying Victimization: Associations with Social Isolation, Gender Differences and Depression in Later Life.

The association between childhood bullying victimization and depression has been well-explored among young adults, but little is known about whether this relationship persists into later life stages, specifically during middle-aged and older phases. Moreover, the intricate mechanisms underpinning this association and the potential existence of gender differences within this context remain inadequately elucidated. To address this gap in knowledge, this study aims to investigate the association between childhood bullying victimization and depression in later life, with a focus on exploring the mediating role of social isolation and the moderating roles of gender. A nationally representative sample of 5,070 individuals (mean age = 61.02, SD = 9.48; male = 55%) was drawn from the China Health and Retirement Longitudinal Study. By employing the bootstrapping analysis method, the mediating role of social isolation was examined, and the moderating role of gender was tested through the generation of interaction items. The results reveal a significant association between childhood bullying victimization and severe depression in later life. Additionally, social isolation plays a mediating role in this association between childhood bullying victimization and social isolation, and the association between social isolation and depression, as well as the relationship between social isolation and depression, are both moderated by gender, presenting stronger effects for female groups than for male groups. However, no moderating role of gender is found in terms of the direct association between childhood bullying victimization and depression. These findings highlight the fact that childhood bullying is not only a problem in the immediate term but also a concern that affects individuals across entire life course. This study has implications for healthcare in proactively investigating, diagnosing, and treating depression by inquiring about childhood bullying victimization experiences. Furthermore, intervention policies that aim to reduce social isolation may be particularly beneficial in mitigating the negative associations, especially for female individuals.

Gut Microbiota Dysbiosis and Inflammation Dysfunction in Late-Life Depression: An Observational Cross-Sectional Analysis.

There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD.

Abstract WMP19: A Brain Care Score for Risk of Late-Life Depression: Data From the UK Biobank Cohort

Introduction: The 21-point Brain Care Score (BCS), developed via a modified Delphi process with practitioners and patients, is a novel instrument designed to motivate behavioral and lifestyle changes, ultimately aiming to decrease incidence of dementia and stroke (Fig 1). Whether or not BCS components are associated with longitudinal changes in mood disorders is not clear. For this study, we tested the hypothesis that the BCS also significantly correlates to late-life depression incidence in the UK Biobank (UKB). Design / Methods: The BCS was derived from UKB participants (using both the hospital and general practitioners cohort) aged 40-69 years, at baseline (2006-2010). After excluding patients with prevalent psychiatric disorders, we performed multivariable Cox proportional hazard regression models between the BCS and risk of incident late-life depression, adjusting for sex and stratified by age groups (&lt;50, 50-59, &gt;59 years). Results: The total BCS (median: 12; IQR:11-14) was derived for 416,370/502,408 (83%) UKB participants with complete data (mean age: 57; females: 54%). After exclusion of 50,395 participants who had mood or psychiatric disorders other than depression, a total of 365,975 participants were included in our analysis. In total, 6,628 incident cases of late-life depression were documented during the median follow-up period of 13 years. Each five-point increase in BCS was associated with a 59% (HR: 0.41, 95% CI: -0.03-0.85) decreased incidence of late-life depression among UKB participants aged &lt;50, 35% (HR: 0.65, 95% CI: 0.57-0.74) among those aged 50-59; and 28% (HR: 0.72, 95% CI: 0.65-0.79) lower risk among those aged &gt;59). Conclusions: In addition to its associations with dementia and stroke incidence, the BCS strongly correlates with late-life depression incidence in the UK Biobank. Additional research is needed to understand the association between BCS elements and late life depression in additional, diverse cohorts.

Abstract WMP21: Life's Essential 8 and Brain Health Clinical Outcomes in Middle-Aged Adults

Background: Mounting evidence points to a connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association’s Life’s Essential 8 (LE8) constitute a research and public health construct capturing key determinants of cardiovascular health. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to brain health. Methods: We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU). We excluded participants with stroke, dementia, or late-life depression (LLD) at baseline. The exposure of interest was the LE8 score, a validated tool that captures the LE8 components (blood pressure, glucose, and cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories. The outcome of interest was a composite of stroke, dementia, or LLD. We evaluated the associations of interest via multivariable Cox proportional hazard models. Results: The discovery stage included 334,505 UKB participants (mean age 56, 47% female), in whom the unadjusted risk of the composite outcome of interest was 471 (0.7%), 2,224 (1.1%) and 1,143 (1.7%) in participants with optimal, intermediate, and poor cardiovascular health (p&lt;0.001). This association remained significant in multivariable Cox models (optimal versus poor cardiovascular health OR 2.14; 95% CI 1.92 - 2.39; p&lt;0.001). The replication stage included 92,551 AoU participants (mean age 57, 59% female), in whom the unadjusted risk of the composite outcome was 547 (3%), 3,451 (6.2%) and 1,833 (10%) in participants with optimal, intermediate, and poor cardiovascular health (p&lt;0.001). This association remained significant in multivariable Cox models (optimal versus poor cardiovascular health OR 2.20; 95% CI 1.99 - 2.42; p&lt;0.001). Conclusions and Relevance: Among middle-aged UKB and AoU participants, poorer LE8 cardiovascular health profiles were strongly associated with a higher risk of developing a composite endpoint that captures the most important diseases related to brain health. These findings support the utilization of this endpoint in clinical trials focused on brain health.

Age-related subtypes of late life depression and mortality: Aprospective clinical cohort study.

Late Life Depression (LLD) is associated with increased mortality rates, but it remains unclear which depressed patients are at increased risk. This study examined the mortality risk of previously identified subgroups of depressed older patients based on age-related clinical features (the presence of physical and cognitive frailty). A six-year follow-up of a clinical cohort study including 375 depressed older patients and 132 non-depressed persons (NESDO). Depressed patients were diagnosed with the Composite International Diagnostic Interview (CIDI) according to DSM-IV criteria and classified by latent profile analysis on depressive symptom severity, cognitive domains and physical frailty. We estimated the hazard rate of mortality for the four depressed subgroups compared to non-depressed persons by applying Cox-regression analyses. Models were adjusted for age, sex and education as confounders and for explanatory variables per pathway in separate models: somatic burden, lifestyle characteristics, vascular burden or inflammation markers. A total of 61/375 (16.3%) depressed patients and 8/132 (6.1%) non-depressed persons died during the 6-year follow-up. Two of the four subgroups (n=186/375 (50%) of the depressed sample) had a higher hazard rate (HR) for mortality compared to non-depressed participants, that is, frail-depressed patients (HR=5.25, [95%-CI: 2.13-13.0]) and pure mild depressed patients (HR=3.32 [95%-CI: 1.46-7.58]) adjusted for confounders. Adding possible underlying pathways did not explain these associations. Age-related features (the presence of physical and cognitive frailty) contribute to the increased mortality risk in late-life depression. Future studies in depressed older patients should study the additional value of a clinical geriatric assessment and integrated treatment aimed to at reduce frailty and ameliorate their mortality risk.

Abstract HUP2: Brain Health Outcomes in Sexual and Gender Minority Groups

Background: There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals. Methods: We conducted a cross-sectional study in the All of Us Research Program, a population study focused on health disparities enrolling 1 million Americans. We used baseline questionnaires to identify participants from sexual minorities (non-straight e.g., gay, lesbian, bisexual) and gender minorities (gender identity different from sex assigned at birth). We further divided gender minorities into gender diverse (e.g., non-binary) and transgender. The primary outcome was a composite of stroke, dementia, and late-life depression. In secondary analyses, we analyzed SGM subgroups and diseases separately. We used multivariate logistic regression to assess the link between SGM groups and brain health outcomes. Results: We included 393,041 participants (mean age 51, female sex at birth 62%), of whom 39,632 (10%) belonged to SGM groups. Of these, 4,431 (1%) belonged to a gender minority (2,212 [50%] gender diverse and 2,219 [50%] transgender) and 38,528 (10%) to a sexual minority. Full results are shown in the Figure. Compared to non-SGM, SGM individuals had 19% higher odds of the brain health composite outcome (OR 1.19, 95%CI 1.13-1.25). These results were consistent across all SGM subgroups (p&lt;0.05). When assessing individual diseases, all SGM groups had higher odds of late-life depression, all SGM except transgender persons had higher odds of dementia, and gender minority groups had higher odds of stroke. Conclusion: In a large US population study, SGM individuals had a higher rate of adverse brain health outcomes. Further research should explore the structural causes of inequity to advance inclusive and diverse neurological care.

Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5years among a clinical cohort with remitted major depressive disorder (MDD). The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p=0.009) and memory (p=0.041) could predict subsequent progression to dementia within 5years among patients with MDD. This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5years.

Abstract 69: Epigenetic Age and Brain Health Events: Findings From the Health and Retirement Study

Introduction: It is increasingly recognized that chronological age provides an incomplete assessment of true biological age. Epigenetic clocks use DNA methylation data to estimate biological age more accurately. We hypothesize that brain health events (BHe) lead to epigenetic age acceleration and that, conversely, accelerated epigenetic age leads to higher risk of BHe. Methods: We conducted a 3-stage epigenetic study within the Health and Retirement Study (Figure). In 2016, participants provided blood samples and methylation and genomic data was generated. Epigenetic age was calculated as the average of thirteen epigenetic clocks that used different combinations of methylation data. BHe was a composite of stroke, dementia and late-life depression. Stage 1 entailed testing for association between BHe prior to 2016 (exposure) and epigenetic age (outcome). Stage 2 entailed testing for association between epigenetic age (exposure) and BHe occurring after 2016 (outcome). Stage 3 entailed testing for causal associations using Mendelian Randomization (MR). Results: Results are summarized in the Figure. Out of 4,018 participants with epigenomic data, 2,221 (55%) had a history of BHe before 2016. A history of BHe was associated with an older epigenetic age (beta 0.05, SE 0.01; p&lt;0.01). Of the 3,047 study participants with available follow-up data, 1,018 (33%) developed a BHe over a mean follow up of 4 years. Epigenetic age acceleration was associated with higher odds of BHe (OR 1.57, [1.22-2.01]). Causal associations estimated via MR analyses confirmed both results. Conclusion: A history of BHe was associated with epigenetic age acceleration and, conversely, epigenetic age acceleration was linked to a higher risk of brain health events. MR analyses suggest that these associations are causal. These results indicate that more nuanced strategies for ascertaining biological age are needed in stroke research and point to epigenetic clocks as a promising tool for this purpose.

Abstract 71: Brain Health Outcomes in Sexual and Gender Minority Groups

Background: There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals. Methods: We conducted a cross-sectional study in the All of Us Research Program, a population study focused on health disparities enrolling 1 million Americans. We used baseline questionnaires to identify participants from sexual minorities (non-straight e.g., gay, lesbian, bisexual) and gender minorities (gender identity different from sex assigned at birth). We further divided gender minorities into gender diverse (e.g., non-binary) and transgender. The primary outcome was a composite of stroke, dementia, and late-life depression. In secondary analyses, we analyzed SGM subgroups and diseases separately. We used multivariate logistic regression to assess the link between SGM groups and brain health outcomes. Results: We included 393,041 participants (mean age 51, female sex at birth 62%), of whom 39,632 (10%) belonged to SGM groups. Of these, 4,431 (1%) belonged to a gender minority (2,212 [50%] gender diverse and 2,219 [50%] transgender) and 38,528 (10%) to a sexual minority. Full results are shown in the Figure. Compared to non-SGM, SGM individuals had 19% higher odds of the brain health composite outcome (OR 1.19, 95%CI 1.13-1.25). These results were consistent across all SGM subgroups (p&lt;0.05). When assessing individual diseases, all SGM groups had higher odds of late-life depression, all SGM except transgender persons had higher odds of dementia, and gender minority groups had higher odds of stroke. Conclusion: In a large US population study, SGM individuals had a higher rate of adverse brain health outcomes. Further research should explore the structural causes of inequity to advance inclusive and diverse neurological care.

Prognosis of Late-Life Depression: Clinical and Immunological Characteristics

Prognosis of Late-Life Depression: Clinical and Immunological Characteristics

Geriatric depression and anxiety screening via deep learning using activity tracking and sleep data.

Geriatric depression and anxiety have been identified as mood disorders commonly associated with the onset of dementia. Currently, the diagnosis of geriatric depression and anxiety relies on self-reported assessments for primary screening purposes, which is uncomfortable for older adults and can be prone to misreporting. When a more precise diagnosis is needed, additional methods such as in-depth interviews or functional magnetic resonance imaging are used. However, these methods can not only be time-consuming and costly but also require systematic and cost-effective approaches. The main objective of this study was to investigate the feasibility of training an end-to-end deep learning (DL) model by directly inputting time-series activity tracking and sleep data obtained from consumer-grade wrist-worn activity trackers to identify comorbid depression and anxiety. To enhance accuracy, the input of the DL model consisted of step counts and sleep stages as time series data, along with minimal depression and anxiety assessment scores as non-time-series data. The basic structure of the DL model was designed to process mixed-input data and perform multi-label-based classification for depression and anxiety. Various DL models, including the convolutional neural network (CNN) and long short-term memory (LSTM), were applied to process the time-series data, and model selection was conducted by comparing the performances of the hyperparameters. This study achieved significant results in the multi-label classification of depression and anxiety, with a Hamming loss score of 0.0946 in the Residual Network (ResNet), by applying a mixed-input DL model based on activity tracking data. The comparison of hyper-parameter performance and the development of various DL models, such as CNN, LSTM, and ResNet contributed to the optimization of time series data processing and achievement of meaningful results. This study can be considered as the first to develop a mixed-input DL model based on activity tracking data for the multi-label identification of late-life depression and anxiety. The findings of the study demonstrate the feasibility and potential of using consumer-grade wrist-worn activity trackers in conjunction with DL models to improve the identification of comorbid mental health conditions in older adults. The study also established a multi-label classification framework for identifying the complex symptoms of depression and anxiety.

Lifetime adversity predicts depression, anxiety, and cognitive impairment in a nationally representative sample of older adults in the United States.

Although life stress and adversity are well-known risk factors for mental health problems and cognitive impairment among older adults, limited research has comprehensively examined the impact of both childhood and adulthood adversity on psychiatric and cognitive impairment symptoms over a prolonged period. To address this issue, we investigated how lifetime adversity exposure is related to symptoms of depression, anxiety, and cognitive impairment in a nationally representative, longitudinal sample of older adults in the United States. We analyzed data from the Health and Retirement Study (1992-2016). The sample included 3496 individuals (59.9% female), aged ≥64 years old (Mage = 76.0 ± 7.6 years in 2016). We used the individual-level panel data and ordinary least squares regressions to estimate associations between childhood and adulthood adversities, and later-life depression, anxiety, and cognitive impairment. Many participants experienced a significant early life (38%) or adulthood (79%) stressor. Moreover, experiencing one childhood adversity (vs. none) was associated with a 17.4% increased risk of adulthood adversity. Finally, as hypothesized, childhood adversity exposure was related to experiencing more depression and anxiety symptoms in later life, whereas adulthood stressor exposure predicted more cognitive impairment as well as more depression and anxiety symptoms. These findings demonstrate significant associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in older adults. Screening for lifetime stressors may thus help healthcare professionals and policymakers identify individuals who could potentially benefit from interventions designed to reduce stress and enhance resilience.

Never Too Late: Safety and Efficacy of Deep TMS for Late-Life Depression

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-established treatment for major depressive disorder (MDD). Deep TMS utilizes specially designed H-Coils to stimulate the deep and broad cerebral regions associated with the reward system. The improved depth penetration of Deep TMS may be particularly important in late-life patients who often experience brain atrophy. The aim of this phase IV open-label study was to evaluate the safety and efficacy of Deep TMS in patients with late-life MDD. Data were collected from 247 patients with MDD aged 60–91 at 16 sites who had received at least 20 Deep TMS sessions for MDD. The outcome measures included self-assessment questionnaires (Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory-II (BDI-II)) and clinician-based scales (21-item Hamilton Depression Rating Scale (HDRS-21)). Following 30 sessions of Deep TMS, there was a 79.4% response and 60.3% remission rate on the most rated scale. The outcomes on the PHQ-9 were similar (76.6% response and 54.7% remission rate). The highest remission and response rates were observed with the HDRS physician-rated scale after 30 sessions (89% response and a 78% remission rate). After 20 sessions, there was a 73% response and 73% remission rate on the HDRS. Consistent with prior studies, the median onset of response was 14 sessions (20 days). The median onset of remission was 15 sessions (23 days). The treatment was well tolerated, with no reported serious adverse events. These high response and remission rates in patients with treatment-resistant late-life depression suggest that Deep TMS is a safe, well-tolerated and effective treatment for this expanded age range of older adults.

Childhood neighbourhood quality, peer relationships, and trajectory of depressive symptoms among middle-aged and older Chinese adults.

This study aimed to examine childhood neighbourhood quality, peer relationships, and trajectories of depressive symptoms among middle-aged and older Chinese adults. The data came from the longitudinal dataset from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018). Depressive symptoms were measured repeatedly using the ten-item Centre for Epidemiologic Studies Depression Scale (CES-D-10). Latent growth modelling was used to capture the trajectory of depressive symptoms by childhood neighbourhood quality, and peer relationships. The mean level of depressive symptoms increased gradually in the follow-up period. Poorer childhood neighbourhood quality, and peer relationships were significantly associated with higher levels of depression in later life (β = 0.18 and β = 0.28 for aged 45-59, p < 0.001; β = 0.16 and β = 0.33 for aged 60 and over, p < 0.001) at baseline and a faster increase in depressive symptoms with age for childhood neighbourhood quality (β = 0.03, p < 0.01 for aged 45-59; β = 0.05, p < 0.01 for aged 60 and over). For males and females, poorer childhood neighbourhood quality, and peer relationships predicted higher levels of depression at baseline (β = 0.17 and β = 0.36 for males, p < 0.001; β = 0.16 and β = 0.27 for females, p < 0.001), and only neighbourhood quality was associated with a higher rate of change in depression during follow-up (β = 0.03, and β = 0.04, p < 0.05, respectively). Poorer childhood neighbourhood quality was associated with the slope of change in depressive symptoms. Efforts towards improving childhood living conditions may help to prevent the detrimental health effects of such early life disadvantages.

Frontal-striatal tract integrity and depression in older adults with and without multiple sclerosis.

Lower white matter integrity of frontal-subcortical circuitry has been associated with late-life depression in normally aging older adults and with the presence of multiple sclerosis (MS). Frontal-striatal white matter tracts involved in executive, cognitive, emotion, and motor function may underlie depression in older adults with MS. The present study examined the association between depression score and frontal-striatal white matter integrity in older adults with MS and controls. Older adults with MS (OAMS) (n = 67, mean age = 64.55 ± 3.89) and controls (n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Depression was assessed through the 30-item Geriatric Depression Scale. Fractional anisotropy (FA) was extracted from two bilateral tracts: dorsolateral prefrontal cortex to putamen nucleus (DLPFC-pn) and dorsolateral prefrontal cortex to caudate nucleus (DLPFC-cn). OAMS reported significantly worse (i.e., higher) depression symptoms (β = .357, p < .001) compared to healthy controls. Adjusted moderation analyses revealed, via group by FA interactions, significantly stronger associations between FA of the left DLPFC-pn tract and total depression (B = - 61.70, p = .011) among OAMS compared to controls. Conditional effects revealed that lower FA of the left DLPFC-pn was significantly associated with worse (i.e., higher) depression symptoms (b = - 38.0, p = .028) only among OAMS. The other three tracts were not significant in moderation models. We provided first evidence that lower white matter integrity of the left DLPFC-pn tract was related to worse depression in older adults with MS.

Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial

BackgroundLate-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. MethodsA 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. ResultsA total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LimitationsSample size is small with only marginal clinical effect. ConclusionThese findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.