Late-life Depression Research Articles

The N-3 polyunsaturated fatty acids supplementation to prevent depression recurrence in patients with late-life depression: A 52-week double-blind, placebo-controlled trial

BackgroundReports on the efficacy of omega-3 fatty acids (n-3 PUFAs) for the treatment of late-life depression (LLD) are mixed, and most studies focus on the modification of depressive symptoms rather than depression prevention. The aim of the present study was to investigate the efficacy of n-3 PUFAs in preventing depressive recurrence in patients with late-life depression. In addition, we investigated the effects of n-3 PUFAs on changes in depressive and anxiety symptoms and inflammatory markers in LLD. MethodsA 52-week, double-blind, randomized, controlled trial was conducted. We enrolled a total of 39 euthymic patients with LLD. They were randomized to receive either n-3 PUFAs (1.2 g per day of eicosapentaenoic acid and 1 g of docosahexaenoic acid) or placebo for 52 weeks. Recurrence of depression and severity of depression symptoms were assessed at baseline and weeks 4, 8, 16, 24, 32, 40, and 52. ResultsA total of 39 patients completed the trial with 19 in the n-3 PUFAs group and 20 in the placebo group. Cox proportional hazard regression indicated that n-3 PUFAs had significant protective effect on depression recurrence (Hazard Ratio: 0.295, 95 % Confidence Interval: 0.093–0.931, p value =0.037). But n-3 PUFAs intervention had no significant effect in reducing depressive or anxiety symptoms, inflammatory markers over the placebo group. LimitationThe results should be interpreted with consideration of the modest sample size. ConclusionThese findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD.

Interaction of the gut microbiota and brain functional connectivity in late-life depression.

Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC. The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.

Anxiety in late-life depression is associated with poorer performance across multiple cognitive domains.

Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains. Older adults with major depressive disorder (N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning. Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity. Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

Chemosensory anhedonia facilitates depressive symptoms and cognitive impairment in late-life depression.

Chemosensory anhedonia refers to the lack of hedonic ability to experience pleasure through the senses of smell and taste, which reduces the pleasure and comfort of food, and increases the risk of nutritional and immune deficiencies. However, there is no direct scientific evidence regarding chemosensory anhedonia in patients with late-life depression (LLD). The aim of this study was to investigate chemosensory anhedonia in patients with LLD, and its potential association with depressive symptoms and cognitive function. A total of 114 patients with LLD and 92 normal controls were included in this study. They experienced clinical assessment, Chemosensory Pleasure Scale assessment, 17-item Hamilton Depression Rating Scale assessment and cognitive assessments, which contain the Verbal Fluency Test. The associations between chemosensory pleasure and depressive symptoms or cognitive function in patients with LLD were explored using partial correlation analysis and mediation analysis. The Chemosensory Pleasure Scale scores were lower in the LLD group than in the normal control group, and were negatively correlated with the total scores and factors' scores (retardation, cognitive bias and anxiety/somatization) of the 17-item Hamilton Depression Rating Scale, and positively correlated with the Verbal Fluency Test scores. The scores for the Food and Imagination dimensions of the Chemosensory Pleasure Scale showed partial mediating effects on the differences in Cognitive bias (a factor of the 17-item Hamilton Depression Rating Scale) between patients with LLD and normal controls. Patients with LLD showed significant chemosensory anhedonia, and both depressive symptoms and cognitive impairment were associated with the severity of chemosensory anhedonia. Enhancing chemosensory pleasure in patients with LLD could potentially ameliorate their depressive symptoms. Geriatr Gerontol Int 2024; ••: ••-••.

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

BackgroundLate-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. ObjectiveThis study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. MethodsA 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. ResultsThe ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. ConclusionThe combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

Odor identification dysfunction in late-life depression with suicidal ideation

BackgroundSuicide is more prevalent among older adults compared to younger individuals. Late-life depression (LLD) poses the highest risk for suicide. However, early recognition of suicidal ideation is challenging. Dysfunction in odor identification (OI), a characteristic of LLD, may hold potential for early identification of suicidal ideation. This study aims to compare OI between LLD patients with suicidal ideation (LLD-S) and LLD patients without suicidal ideation (LLD-NS), and examine its relationship with cognitive function. MethodsA total of 262 LLD-NS patients, 63 LLD-S patients, and 316 healthy normal older adults (HOAs) underwent OI testing, standardized clinical interviews, and comprehensive neuropsychological assessments. Results(1) LLD-S patients exhibited lower OI scores and poorer cognitive performance (including global cognition, information processing speed, memory, language, executive function, and visuospatial ability) compared to LLD-NS patients and HOAs. (2) There were interactive effects between suicidal ideation and OI dysfunction, leading to lower scores in information processing speed and visuospatial ability. (3) OI dysfunction mediated the differences in cognition between the LLD-NS and LLD-S groups. LimitationsThe present study was a cross-sectional design. ConclusionsLLD-S patients had worse odor identification than LLD-NS patients and HOAs, suggesting that OI testing could be a valuable approach for identifying suicidal ideation in LLD and screening for suicide risk. The presence of both OI impairment and suicidal ideation was associated with poorer cognitive performance in LLD.

Adverse Childhood Experiences and Cognitive Change in Late-Life Depression

ObjectivesTo determine the relationship of adverse childhood experiences (ACEs) with change in cognitive performance over a 1-year period among older adults in treatment for depression. MethodsOlder depressed adults completed the ACEs questionnaire and the Consortium to Establish a Registry of Alzheimer's disease (CERAD) cognitive battery at baseline and were re-assessed with the CERAD 1 year later. ResultsChildhood physical abuse, sexual abuse, and verbal/emotional abuse, respectively, were reported by 25%, 17.5%, and 42% of participants. Total ACEs score was not associated with baseline cognitive performance or 1-year change. However, sexual abuse, physical abuse, and a measure of cumulative verbal/emotional, physical, and sexual abuse were inversely associated with 1-year change in total CERAD score. ConclusionsChildhood abuse may have long-term adverse effects, including placing depressed older adults at risk for progressive cognitive decline. ACEs should be considered in research and clinical management of depression in older adults.

A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary.

Brain Age Is Not a Significant Predictor of Relapse Risk in Late-Life Depression

BackgroundLate-life depression (LLD) has been associated cross-sectionally with lower brain structural volumes and accelerated brain aging compared with healthy control participants (HCs). There are few longitudinal studies on the neurobiological predictors of recurrence in LLD. We tested a machine learning brain age model and its prospective association with LLD recurrence risk. MethodsWe recruited individuals with LLD (n = 102) and HCs (n = 43) into a multisite, 2-year longitudinal study. Individuals with LLD were enrolled within 4 months of remission. Remitted participants with LLD underwent baseline neuroimaging and longitudinal clinical follow-up. Over 2 years, 43 participants with LLD relapsed and 59 stayed in remission. We used a previously developed machine learning brain age algorithm to compute brain age at baseline, and we evaluated brain age group differences (HC vs. LLD and HC vs. remitted LLD vs. relapsed LLD). We conducted a Cox proportional hazards model to evaluate whether baseline brain age predicted time to relapse. ResultsWe found that brain age did not significantly differ between the HC and LLD groups or between the HC, remitted LLD, and relapsed LLD groups. Brain age did not significantly predict time to relapse. ConclusionsIn contrast to our hypothesis, we found that brain age did not differ between control participants without depression and individuals with remitted LLD, and brain age was not associated with subsequent recurrence. This is in contrast to existing literature which has identified baseline brain age differences in late life but consistent with work that has shown no differences between people who do and do not relapse on gross structural measures.

Lifestyle factors, physical health, and life satisfaction under different changes in depressive symptoms among Chinese community-dwelling older adults: A longitudinal analysis.

The study aims to investigate the long-term impact of lifestyle-related factors and physical health on life satisfaction and depressive symptoms among Chinese community-dwelling older adults. Using data from the China Health and Retirement Longitudinal Study (CHARLS), the analytic sample of this study included 1,068 older adults who had participated in the surveys in both 2011 and 2018. Multivariate regression was employed to analyze both cross-sectional and longitudinal relationships between lifestyle-related factors, physical health, and subjective well-being - specifically depressive symptoms and life satisfaction. Additionally, the model tested how these factors correlate with life satisfaction across different groups of depressive symptom changes among older adults, categorized as not at risk of depression, intermittent depression, and chronic depression. Multimorbidity was significantly related to baseline and follow-up depressive risk in older adults. Shorter sleep duration was associated with baseline depression risk. Current alcohol drinkers reported significantly more severe depressive symptoms than non-drinkers. At baseline, current smokers were more likely to have a lower degree of life satisfaction than nonsmokers. Among older adults with chronic depression at the 7-year follow-up, former smokers tended to have lower life satisfaction than nonsmokers. Our findings identified drinking alcohol and having a shorter sleep duration as modifiable lifestyle-related risk factors for late-life depression and smoking as a detrimental factor for life satisfaction in older Chinese adults. Multimorbidity was a significant predictor of more depressive symptoms. Our findings have implications for future psychosocial interventions that target the alleviation of depressive symptoms and the promotion of life satisfaction in older Chinese people based on their different long-term mental and physical health conditions.

Choice intention for the national volume-based procurement drug and its associated factors: a cross-sectional study on patients with late-life depression in China

BackgroundThe national volume-based procurement (NVBP) policy has significantly decreased prices and increased the accessibility of NVBP drugs. Nevertheless, issues such as heightened adverse reactions and suboptimal efficacy have arisen. Concerns regarding the quality of low-cost medications and the absence of long-term research have been widely recognized. This has led to caution among patients with late-life depression (LLD) due to their delicate health and the severity of their condition. This study evaluated the choice intention for NVBP drugs and associated factors in older patients with LLD.MethodsA weighted sample of 408 participants between December 2022 and March 2023 were included. Data were collected via face-to-face interviews and questionnaires. To identify significant associated factors of choice intention, a multilevel logistic regression model was employed.ResultsOver half (53.68%) of older patients with LLD intended to choose NVBP drugs. Associated factors included self-assessed poor economy, higher out-of-pocket expenses, monthly household income exceeding CNY 6000, absence of other non-communicable chronic diseases, ordinary registration, urban employee medical insurance, no requirements for brand-name drugs, adverse reactions after using NVBP drugs, and rejection of physicians’ recommendation for NVBP drugs. The interaction effect between the real economic condition and patients self-assessed economy significantly influences choice intention for NVBP drugs. Among 124 patients with self-assessed poor economy, 75 showed a higher intention to use NVBP drugs. In these patients, age, medical insurance reimbursement, and brand awareness were significantly associated with choice intention.ConclusionEconomic factors, physical conditions, medical needs, and physician recommendations significantly influenced the choice intention for NVBP drugs. The choice intention can be improved by strengthening physician-patient communication, increasing the scope and proportion of medical insurance reimbursement, improving substitution studies, and conducting post-marketing re-evaluations of NVBP drugs.

Fast-acting antidepressant-like effects of ketamine in aged male rats

BackgroundThe aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces the efficacy of classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates to be explored in the context of aging, especially given the lack of previous research on its efficacy for this age period. Thus, the aim of the present study was to characterize ketamine’s effects in older rats.MethodsThe fast-acting (30 min) and repeated (7 days) antidepressant-like effects of ketamine (5 mg/kg, ip) were evaluated in 14-month-old single-housed rats through the forced-swim and novelty-suppressed feeding tests. In parallel, the modulation of neurotrophic-related proteins (i.e., mBDNF, mTOR, GSK3) was assessed in brain regions affected by the aging process, prefrontal cortex and hippocampus, as well as possible changes in hippocampal cell proliferation.ResultsAcute ketamine induced a fast-acting antidepressant-like response in male aged rats, as observed by a reduced immobility in the forced-swim test, in parallel with a region-specific increase in mBDNF protein content in prefrontal cortex. However, repeated ketamine failed to induce antidepressant-like efficacy, but decreased mBDNF protein content in prefrontal cortex. The rate of hippocampal cell proliferation and/or other markers evaluated was not modulated by either paradigm of ketamine.ConclusionsThese results complement prior data supporting a fast-acting antidepressant-like effect of ketamine in rats, to further extend its efficacy to older ages. Future studies are needed to further clarify the lack of response after the repeated treatment as well as its potential adverse effects in aging.

Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models and tractometry

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

Experts Advise How to Maximize Treatment of Late-Life Depression

Experts Advise How to Maximize Treatment of Late-Life Depression

Poor Sleep is Common in Treatment-Resistant Late-life Depression and Associated With Poorer Antidepressant Response: Findings From the OPTIMUM Clinical Trial

BackgroundAdults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep. MethodsSecondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the beginning (week-0) and end (week-10) of treatment. The analyses examined whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep during depression treatment. ResultsAbout half (51%, n = 323) of participants reported insufficient sleep at baseline. Both persistent insufficient sleep (25%, n = 158) and worsened sleep (10%, n = 62) during treatment were associated with antidepressant nonresponse. Participants who maintained sufficient sleep (26%, n = 164) or who improved their sleep (n = 25%, n = 158) were three times more likely to experience a depression response than those with persistent insufficient sleep or worsened sleep. ConclusionInsufficient sleep is common in TRLLD and it is associated with poorer treatment response to antidepressants.

Exploring the relationship between social activities and financial risk aversion in adults aged 50 + with depression caseness

BackgroundRisk aversion due to depression is common among older adults, and social participation is associated with improved mental health and a lower risk of late-life depression. However, little is known about the connection between participation in social activities and risky financial decisions among adults with depression. Thus, we aim to examine the connection between participation in social activities and taking financial risks and investing in risky financial assets (with high-return potential) in such individuals, differentiated by age and gender. The study also focuses on analyzing the percentage of investors within each social activity, their attendance frequency, and motivation.MethodsThe data was obtained from the Survey of Health, Ageing and Retirement in Europe (SHARE) database Wave 2 (2006–2010). The study included 8,769 individuals aged 50 + with depression caseness, from 15 European countries and Israel who answered the question on participation in social activities and reported financial risk-taking intentions or behaviors (investing in stocks or shares, mutual funds or managed investment accounts, and both). The study utilized Pearson chi-square, odds ratios, Z, and hierarchical logistic regression tests.ResultsThe odds for taking financial risks and investing in risky financial assets were higher for those participating in social activities compared to those who did not, on both intentional (by 173%) and behavioral (by 240–397%) levels. Such social activities (attended at least once a week, without financial motivation) have been shown to be primarily represented by educational or training courses — where 33% of participants invested in risky financial assets. The connection persisted after controlling for gender, age, marital status, children, income.ConclusionsBy overcoming the subjects’ financial risk aversion, participation in social activities may help improve mental health in individuals aged 50 + with depression caseness. This has important implications for policymakers in healthcare, who by updating healthcare policies can fund and facilitate participation in social activities. As a result, the national healthcare system may benefit from lower hospitalization-related expenses, and generate higher cash flows into the country’s economy using the population’s renewed interest in investing available funds. These results are relevant in the wake of COVID-19 that increased loneliness and depression rates.

Prevalence and factors associated with depression among the elderly in rural areas of central India: a mixed method study

Background: The global demographic shift towards an aging population has raised concerns about the mental health of the elderly, particularly in rural areas. This study sought to tackle this issue by quantitatively evaluating the prevalence of geriatric depression in rural areas of central India and qualitatively investigating the factors that contribute to late-life depression. Methods: This mixed-method study conducted in the rural areas of central India aimed to assess the prevalence of depression among the elderly and explore gender-specific factors contributing to late-life depression. Results: Quantitative data were collected from 308 elderly individuals aged 60 years and above, revealing a high prevalence of depressive symptoms (75.6%). Factors significantly associated with depression included female gender, age over 70 years, lower educational attainment, financial dependency, and comorbidities. Qualitative analysis through focus group discussions highlighted gender-specific perceptions of depression risk factors, emphasizing the need for tailored interventions. Conclusions: The findings underscore the urgent need for targeted mental health interventions addressing socio-economic disparities and gender-specific challenges in rural elderly populations. A nuanced, gender-sensitive approach is crucial for promoting well-being and reducing the burden of depression among the elderly in rural central India.

Efficacy and Side Effects of Mixed-Strategy Electroconvulsive Therapy: A Proof-of-Concept Randomized Clinical Trial on Late Life Depression.

Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects. This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center

BackgroundDepression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD.MethodsWe conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data.ResultsThe initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD.ConclusionsOur analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

The predictive validity of a Brain Care Score for late-life depression and a composite outcome of dementia, stroke, and late-life depression: data from the UK Biobank cohort.

The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression. The BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth. A total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%). These data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide.