Late-life Depression Research Articles

From starvation to depression: unveiling the link between the great famine and late-life depression

BackgroundThe Great Famine in China from 1959 to 1961 is recognized as one of the most severe social and public health disasters of the 20th century, with profound long-term impacts on the health of survivors, particularly on their mental health. Early-life malnutrition and psychological trauma are considered to contribute to a range of health issues in adulthood, including depression.ObjectiveThis study aims to explore how the experience of the Chinese Great Famine from 1959 to 1961 affects the risk of depressive symptoms among the elderly. Using a mechanism analysis, the study investigates the roles of social support, socioeconomic status, and intergenerational support in this process.MethodsUsing micro-level individual data from the China Health and Retirement Longitudinal Survey (CHARLS), combined with province-level excess mortality data, this study employs a cohort-based difference-in-differences model to identify the causal effects of the famine experience on depression levels among the elderly.ResultsThe study reveals that experiencing the Great Famine significantly increases the risk of depression among the elderly. This effect is more pronounced among rural residents, those who experienced the famine during adolescence, and in regions less influenced by Confucian culture. The mechanism analysis indicates that diminished social support, lower socioeconomic status, and insufficient intergenerational support are the primary pathways through which the famine experience influences depression levels in the elderly.ConclusionsThe experience of the Great Famine has exerted a long-term and profound impact on the mental health of the elderly in China, particularly in terms of depression. The findings provide new perspectives on understanding the long-term effects of major historical events on health and offer important empirical evidence for the development of mental health intervention policies for the elderly.

Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies

Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies

Prediction of electroconvulsive therapy response and remission in late-life depression: a review

Electroconvulsive therapy is an effective and well-tolerated antidepressant treatment for the elderly population. The place of electroconvulsive therapy in the treatment sequence for depression in the elderly is currently not well established. This review aims to identify the factors that contribute to a positive response and remission in elderly patients with depression undergoing electroconvulsive therapy treatment. We searched five bibliographic databases (Medline ALL Ovid, Embase.com, APA PsycInfo Ovid, Cochrane Library Wiley and Web of Science Core Collection) for articles published between 1995 and June 2023. Of the 2149 articles screened, 19 were included in the review. No significant associations were found between remission and/or response and salivary cortisol, baseline hippocampal and white matter hyperintensities, total amyloid load or global cortical atrophy. The reviewed articles did not show a significant difference in remission between unilateral and bilateral electroconvulsive therapy treatment. Other interesting findings are that moderately elevated levels of CRP and S100B levels, lower retardation scores, poorer performance on the word reading task at baseline and longer post-ictal reorientation time may be associated with higher remission and/or response rates. Medial temporal atrophy can be associated with lower Montgomery-Åsberg Depression Rating Scale (MADRS) decrease after electroconvulsive therapy. Finally, elderly patients had higher rates of electroconvulsive therapy response; retardation and psychotic features may mediate this association. Incorporation of this data into clinical practice may facilitate a personalised approach to electroconvulsive therapy. However, research on this topic is scarce and there are few studies that focus specifically on older people.

Characteristics of Severe Late-Life Depression in the Prodromal Phase of Neurodegenerative Dementia

ObjectiveLate-life depression (LLD) is associated with neurodegenerative disease. The clinical characteristics of patients with LLD who develop neurodegenerative dementia or mild cognitive impairment (MCI) have not been thoroughly investigated. There has also been evidence that the severity of depression affects the transition to dementia. However, the clinical characteristics of the most severely depressed patients who receive the electroconvulsive therapy (ECT) and subsequently transition to a diagnosis of neurodegenerative disease remain unclear. MethodWe conducted a retrospective chart review of patients who received ECT between April 2012 and September 2022 at our academic hospital. We compared the clinical characteristics of individuals who transitioned to a diagnosis of neurodegenerative diseases and those whose diagnoses remained stable over a follow-up period of more than one year. ResultsOf the 94 patients who underwent ECT, 12 (13%) were diagnosed with neurodegenerative disease 20 months after their last ECT session. These patients had an older age of onset (p = 0.01) , fewer melancholic features (p = 0.03) , and fewer family histories of psychiatric disorders (p = 0.01) than those whose diagnoses did not change. ConclusionsIt is clinically important to consider the potential transition of older individuals with severe depression to neurodegenerative dementia or MCI, especially in cases characterized by an older age of onset, lack of melancholic features, or absence of a family history of psychiatric disorders.

Brain inflammaging in the pathogenesis of late-life depression.

Late-life depression (LLD) is a prevalent mental disorder among older adults. Previous studies revealed that many pathologic factors are associated with the onset and development of LLD. However, the precise mechanisms that cause LLD remain elusive. Aging induces chronic inflammatory changes mediated by alterations of immune responses. The chronic systemic inflammation termed "inflammaging" is linked to the etiology of aging-related disorders. Aged microglia induce senescence-associated secretory phenotype (SASP) and transition to M1-phenotype, cause neuroinflammation, and diminish neuroprotective effects. In addition, there is an age-dependent loss of blood-brain barrier (BBB) integrity. As the BBB breakdown can lead to invasion of immune cells into brain parenchyma, peripheral immunosenescence may cause microglial activation and neuroinflammation. Therefore, it is suggested that these mechanisms related to brain inflammaging may be involved in the pathogenesis of LLD. In this review, we described the role of brain inflammaging in LLD. Pharmacologic approaches to prevent brain inflammaging appears to be a promising strategy for treating LLD.

Brain Health Outcomes in Sexual and Gender Minority Groups: Results From the All of Us Research Program.

Sexual and gender minority (SGM) groups have been historically underrepresented in neurologic research, and their brain health disparities are unknown. We aim to evaluate whether SGM persons are at higher risk of adverse brain health outcomes compared with cisgender straight (non-SGM) individuals. We conducted a cross-sectional study in the All of Us Research Program, a US population-based study, including all participants with information on gender identity and sexual orientation. We used baseline questionnaires to identify sexual minority (lesbian, gay, bisexual, diverse sexual orientation; nonstraight sexual orientation) and gender minority (gender diverse and transgender; gender identity different from sex assigned at birth) participants. The primary outcome was a composite of stroke, dementia, and late-life depression, assessed using electronic health record data and self-report. Secondarily, we evaluated each disease separately. Furthermore, we evaluated all subgroups of gender and sexual minorities stratified by sex assigned at birth. We used multivariable logistic regression (adjusted for age, sex assigned at birth, race/ethnicity, cardiovascular risk factors, other relevant comorbidities, and neighborhood deprivation index) to assess the relationship between SGM groups and the outcomes. Of 413,457 US adults enrolled between May 31, 2017, and June 30, 2022, we included 393,041 participants with available information on sexual orientation and gender identity (mean age 51 [SD 17] years), of whom 39,632 (10%) belonged to SGM groups. Of them, 38,528 (97%) belonged to a sexual minority and 4,431 (11%) to a gender minority. Compared with non-SGM, SGM persons had 15% higher odds of the brain health composite outcome (odds ratio [OR] 1.15, 95% CI 1.08-1.22). In secondary analyses, these results persisted across sexual and gender minorities separately (all 95% CIs > 1). Assessing individual diseases, all SGM groups had higher odds of dementia (SGM vs non-SGM: OR 1.14, 95% CI 1.00-1.29) and late-life depression (SGM vs non-SGM: OR 1.27, 95% CI 1.17-1.38) and transgender women had higher odds of stroke (OR 1.68, 95% CI 1.04-2.70). In a large US population study, SGM persons had higher odds of adverse brain health outcomes. Further research should explore structural causes of inequity to advance inclusive and diverse neurologic care.

Effects of open-skill and closed-skill exercise on subthreshold depression in female adolescents: A randomized controlled trial

BackgroundSubthreshold depression (SD) affects a significant proportion of adolescent females, posing a risk of major depression in later life. This study examines the effects of open-skill exercise (OSE) and closed-skill exercise (CSE) on SD, executive function (EF), and emotional states in female adolescents. MethodsA double-blind randomized controlled trial involved 95 female adolescents (mean age = 16.73 ± 0.42 years) with SD symptoms. Participants were assigned to OSE, CSE, or control (CON) groups and underwent an 8-week exercise program. Primary outcomes were assessed using the Beck Depression Inventory (BDI-13) and the Center for Epidemiological Studies Depression Scale (CES-D), with secondary outcomes including EF tasks and emotional assessments. Differences were examined using generalized linear mixed models with intention-to-treat and multiple imputation. ResultsBoth OSE and CSE significantly reduced depressive symptoms, with CSE showing greater improvement. EF assessments showed enhanced cognitive flexibility and working memory in both exercise groups at 4 weeks, and superior inhibitory control and cognitive flexibility in the CSE group at 8 weeks. Emotional assessments indicated a notable reduction in negative emotions in the CSE group after 8 weeks. ConclusionsBoth OSE and CSE reduce SD symptoms in female adolescents, with CSE providing more sustained benefits for EF and emotional states. Further research on exercise interventions for mental health is warranted.Trial registration number: ChiCTR2400081139

Amyloid deposition and its association with depressive symptoms and cognitive functions in late-life depression: a longitudinal study using amyloid-β PET images and neuropsychological measurements

BackgroundAlthough depression is linked to an increased risk of dementia, the association between late-onset depression (LOD) and amyloid burden remains unclear. This study aimed to determine amyloid deposition in patients with LOD compared to healthy controls (HC) using amyloid-beta (Aβ) positron emission tomography (PET) images and neuropsychological assessments.MethodsForty patients first diagnosed with major depressive disorder after the age of 60 (LOD) and twenty-one healthy volunteers (HC) were enrolled. Depression and anxiety were evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale. Cognitive function was assessed using the Korean versions of the Mini-Mental Status Examination, Montreal Cognitive Assessment, and Seoul Neuropsychological Screening Battery at baseline and 3-month follow-up. 18F-florbetapir PET images were co-registered with T1-weighted magnetic resonance images.ResultsThere was no significant difference in Aβ deposition between LOD and HC groups. No significant correlation between Aβ burden and depressive symptom severity was found in LOD patients. Higher somatic anxiety was correlated with lower Aβ burden in multiple brain regions, including the left inferior frontal lobe (p = 0.009), right anterior cingulate (p = 0.003), and right superior frontal lobe (p = 0.009). Despite cognitive recovery in areas such as attention (Digit Span Forward, p = 0.026), memory (Auditory Verbal Learning Test Recall Total, p = 0.010; Rey Complex Figure Test Delayed Recall, p = 0.039), and frontal executive function (Contrasting Program, p = 0.033) after three months of antidepressant treatment, cognitive improvement showed no association with amyloid deposition.ConclusionsThese findings suggest distinct mechanisms may underlie amyloid deposition in neurodegenerative changes associated with depression. While amyloid burden in specific brain regions negatively correlated with somatic anxiety, it showed no significant correlation with the severity of depression or overall cognitive function.

The Associations Between Social Support From Adult Children (SSAC) and the Risk of Later-Life Depression (LLD) Among Rural Older Individuals: A Longitudinal Study Based on 2011 to 2018 China Health and Retirement Longitudinal Study Data.

This study was designed to investigate the implications of perceived social support from adult children (SSAC) on the incidence of later-life depression (LLD) among rural older adults in China. A total of 1762 participants without depressive symptoms and aged ≥60years at baseline were recruited from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study (CHARLS) and followed up until 2018. After following-up for 2-7years (average 4.6years), a total of 746 participants (43.2%) were identified with LLD and the overall incidence of LLD was 128.5 per 1000 person-years. Univariate and multiple Cox regression analysis consistently indicated that receiving living care support was the sole form of SSAC that may significantly reduce the risk of LLD in rural older adults in China (HR: 0.81, 95% CI: 0.70-0.95, p = .008). These results may be of assistance in comprehensively understanding the role of SSAC in the mental health of older adults.

The mediating effect of problem-focused coping on the relationship between emotional clarity and mental health among older adults.

Individuals who can recognize emotions well are better able to identify and accept their feelings and manage them. This study examined the mediation of problem-focused coping in the pathway through which emotional clarity predicts higher life satisfaction and lower depression in older adults. In total, 150 older adults (75 male and 75 female, aged 60-69 years, with a mean of 64.53 [SD = 2.49]) participated in a face-to-face survey, answering questions on emotional clarity, problem-focused coping, life satisfaction, and depression. Emotional clarity was associated with higher life satisfaction and lower depression in older adults. People who were aware of their emotions well were in better emotional condition. Mediation analysis revealed that problem-focused coping mediated the positive relationship between emotional clarity and life satisfaction and the negative relationship between emotional clarity and depression. Older adults who understand their own emotions tend to deal with emotional events in a problem-focused manner, leading to high life satisfaction and low depression. This study identifies cognitive conditions for increasing life satisfaction and preventing depression in later life and offers suggestions for personal and social efforts to maintain mental health.

Association between sleep duration from midlife to late life and the risk of depressive symptoms: the Singapore Chinese Health Study.

The prospective association between sleep duration and the development of late-life depressive symptomology is unclear. To investigate sleep duration from midlife to late life in relation to risk of depressive symptoms in late life. A total of 14 361 participants from the Singapore Chinese Health Study were included in the present study. Daily sleep duration was self-reported at baseline (mean age of 52.4 years; 1993-98), follow-up 2 (mean age of 65.2 years; 2006-10) and follow-up 3 (mean age of 72.5 years; 2014-16) interviews. Depressive symptoms were evaluated using the Geriatric Depression Scale at follow-up 3 interviews. Modified Poisson regression models were performed to estimate relative risks and 95% confidence intervals of late-life depressive symptoms in relation to sleep duration at baseline and the two follow-up interviews. Compared with sleeping 7 h per day, a short sleep duration of ≤5 h per day at baseline (i.e. midlife) was related to a higher risk of depressive symptoms (relative risk 1.10, 95% CI 1.06-1.15), and this risk was not affected by subsequent prolongation of sleep. Conversely, a long sleep duration of ≥9 h per day at baseline was not related to risk of depressive symptoms. At follow-up 3 (i.e. late life), both short sleep (relative risk 1.20, 95% CI 1.16-1.25) and long sleep (relative risk 1.12, 95% CI 1.07-1.18) duration were cross-sectionally associated with depressive symptoms. Short sleep duration in midlife, regardless of subsequent prolongation, is associated with an increased risk of depression in late life. Contrariwise, both short and long sleep duration in late life co-occur with depressive symptoms.

Is Common Denominator Lead to Misdiagnosis of Dementia and Late-Life Depression

Significant cognitive impairments are found in late life depression. This situation brings to mind the question of what are the common and distinct mechanisms of late life depression and dementia. In this review, neural and psychological mechanism are discussed within the scope of denominator and hallmark for both disorders. It is searched several databases e.g. MEDLINE, Web of Science Core Collection from 1974 to 2024 by using variant terms for the focal epilepsy subtypes and social cognition constructs. The pathology of dementia was correlated with late-life depression Studies indicate that depression may be an etiological factor for dementia as well as an increased risk. Also, many life-related stressors can lead to results such as increased reactive oxygen species, inflammatory responses, suppression of neurogenesis, and apical dendritic atrophy and altered functional connectivity in the medial prefrontal cortex. Based on this, it is possible to say that psychological stress factors increase the incidence of the disease in the development of dementia, just like in depression. Late depression should not be labeled as dementia because of they share similar symptoms and should be evaluated clinically correct so that it is not misdiagnosed. Besides, it is substantial to comprehend the relationship between the aging population and the risk of depression and dementia for current and future studies, especially in terms of prevention and treatment.

Efficacy of problem-solving therapy in treating late-life depression with potential cognitive impairment: a systematic review and meta-analysis.

Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings. The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital. CRD42023473782.

The Cognitive Profile of Older Adults With Treatment-Resistant Depression: An Analysis of the OPTIMUM Randomized Controlled Trial

ObjectiveMajor depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy. DesignSecondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD. SettingFive outpatient academic medical centers (4 US, 1 Canada). ParticipantsAbout 369 participants aged 60 and older from the OPTIMUM study. MeasurementsBaseline scores on individual tasks and composite scores from the NIH Toolbox-Cognition Battery were transformed into demographically-adjusted T-scores and compared to published norms. Impairments in the set shifting and inhibitory control tasks were investigated as predictors of depressive symptom change following treatment using ANCOVA models. ResultsParticipants had low performance on tasks evaluating inhibitory control, processing speed, verbal/nonverbal memory, and the fluid composite, but normative performance on working memory and set shifting. Participants had high estimated premorbid IQ (superior Performance on oral reading recognition). Age and physical comorbidity negatively associated with processing speed. Impairments in set shifting predicted less improvement in depressive symptoms; impairments in inhibitory control did not. ConclusionsParticipants with TR-LLD presented with broad cognitive deficits relative to healthy norms. Given poorer outcomes following standard pharmacotherapy associated with impaired set shifting, future research needs to identify alternative treatment strategies.

Gait speed, handgrip strength, and their combination, and risk of depression in later life: Evidence from a prospective study of community-dwelling older adults

ObjectiveThis study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults. MethodsA secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders. ResultA total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11–1.29 and 1.14; 1.06–1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16–1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression. LimitationsAlthough the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression. ConclusionLow physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life.

Socioeconomic status and depression in later life: longitudinal mediation effects of activities of daily living

BackgroundSocioeconomic status (SES) is associated with both depression and activities of daily living (ADL and IADL). However, the role of ADL as a biological mechanism in the relationship between SES and late-life depression, examined through longitudinal data, remains understudied. This study explored the longitudinal mediation effects of basic ADL or IADL on the SES-depression link in older adults.MethodsData from the China Health and Retirement Longitudinal Study (N = 4104) were utilized. Mediation analysis was performed using parallel process latent growth curve modeling.ResultsThe average age of participants was 57.76 years, and 55.7% being females. Significant linear growth over time was observed in ADL, IADL, and depression. Adjusting for covariates, SES was positively linked to the initial levels (intercepts) of ADL (βiADL=-0.100[-0.143, -0.057]), IADL (βiIADL=-0.140[-0.185, -0.095]), and depression (βiDEP=-0.103[-0.158, -0.048]). However, SES showed no significant correlation with the rate of change (slopes) in ADL, IADL, or depression (P > 0.05). The intercepts of ADL (βiDEP = 0.566[0.503, 0.629]) and IADL (βiDEP = 0.607[0.544, 0.670]) were positively correlated with the depression intercept but negatively with the depression slope. Conversely, the slopes of ADL and IADL were positively associated with the depression slope. These results suggest a negative indirect relationship between SES and the initial level of depression, but a positive indirect relationship with the rate of increase in depression through ADL (or IADL) intercept.ConclusionsHigher SES is associated with a lower initial risk of depression and ADL difficulties. However, this same higher SES may relate to a faster increase in ADL difficulties and depression among middle-aged and older adults. The findings underscore the need for increased governmental healthcare funding and improved healthcare accessibility. Additionally, maintaining adequate sleep and physical activity can help prevent disability and reduce depression risk later in life, particularly among older adults with lower SES.

Nine Neuroimaging-AI Endophenotypes Unravel Disease Heterogeneity and Partial Overlap across Four Brain Disorders: A Dimensional Neuroanatomical Representation.

Disease heterogeneity poses a significant challenge for precision diagnostics. Recent work leveraging artificial intelligence has offered promise to dissect this heterogeneity by identifying complex intermediate brain phenotypes, herein called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine such DNEs derived from independent yet harmonized studies on Alzheimer's disease (AD1-2)1, autism spectrum disorder (ASD1-3)2, late-life depression (LLD1-2)3, and schizophrenia (SCZ1-2)4, in the general population of 39,178 participants in the UK Biobank study. Phenome-wide associations revealed prominent associations between the nine DNEs and phenotypes related to the brain and other human organ systems. This phenotypic landscape aligns with the SNP-phenotype genome-wide associations, revealing 31 genomic loci associated with the nine DNEs (Bonferroni corrected P-value < 5×10-8/9). The DNEs exhibited significant genetic correlations, colocalization, and causal relationships with multiple human organ systems and chronic diseases. A causal effect (odds ratio=1.25 [1.11, 1.40], P-value=8.72×10-4) was established from AD2, characterized by focal medial temporal lobe atrophy, to AD. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors, and chronic diseases. All results are publicly available at https://labs-laboratory.com/medicine/.

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.