The combination of antidepressant and antipsychotic medication is an effective treatment for major depressive disorder with psychotic features ('psychotic depression'). The present study aims to identify sociodemographic and clinical predictors of remission of psychotic depression treated with combination pharmacotherapy and determine the accuracy of prediction models.

Two hundred and sixty-nine participants aged 18 to 85 years with psychotic depression were acutely treated with protocolized sertraline plus olanzapine for up to 12 weeks. Three cross-validated machine learning models were implemented to predict remission based on 74 sociodemographic and clinical variables measured at acute baseline. The optimal model for each method was selected by the average fold C-index. Based on the performance of each method, grouped elastic net (cox) regression was chosen to examine the association of each predictor with remission of psychotic depression.

Of the 269 participants, 145 (53.9 %) experienced full remission of the depressive episode and psychotic features. Multivariable models had 65.1 % to 67.4 % accuracy in predicting remission. In the grouped elastic net (cox) regression model, longer duration of index episode, somatic or tactile hallucinations, higher burden of comorbid physical problems, and single or divorced marital status were independent predictors of longer time to remission. A higher number of lifetime depressive episodes and peripheral vascular or cardiovascular disease were predictors of shorter time to remission.

Future research needs to determine whether the addition of biomarkers to clinical and sociodemographic variables can improve model accuracy in predicting remission of pharmacologically-treated psychotic depression.

Early-onset depression (EOD) and late-onset depression (LOD) are prevalent subtypes of major depressive disorder (MDD), but the clinical distinction between EOD and LOD remains blurred due to nonspecific symptoms and lack of biomarkers. This study aims to elucidate the characteristics in cognitive function and biochemical metabolism of EOD and LOD, and to identify biological factors influencing age of onset (AOO).

Seventy patients with MDD (40 with EOD and 30 with LOD) and sixty-eight age-matched healthy controls (HC) were included in this study. Participants were evaluated for clinical features, cognitive function, and serum trace elements levels. Proton magnetic resonance spectroscopy (1H-MRS) was employed to quantify neurometabolites levels, including N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr).

Patients with LOD experienced more episodes and severe depressive symptoms than those with EOD (p = 0.025, p < 0.001). EOD patients performed significantly worse than LOD patients on social cognition (p = 0.005), while LOD patients performed worse than EOD patients on reasoning and problem solving (p = 0.005). Additionally, LOD patients displayed higher ceruloplasmin (Cp) levels compared to EOD patients (p = 0.004), but no difference was found in neurometabolic levels between EOD and LOD. Multiple linear regression indicated a positive correlation between serum Cp levels and AOO of depression (p < 0.001), while bilateral thalamic NAA/Cr showed a negative correlation with AOO (p = 0.012, p = 0.016).

Patients with EOD were characterized by social cognition impairments, while patients with LOD were marked by reasoning and problem-solving deficits. Serum Cp levels demonstrated an AOO-related effect and served as a positive predictor for the AOO of depression. Furthermore, a negative correlation has been established between bilateral thalamic NAA/Cr and the AOO of MDD.

The limited sample size and the challenge in distinguishing whether observed results are attributed to age or AOO effects.

Vascular depression (VaDep), which was proposed over two decades ago, is a distinct subtype of depression primarily observed in patients with stroke and cerebral small-vessel disease and is characterized by white matter hyperintensities; however, the lack of standardized diagnostic criteria and consensus limits its clinical application. This review explores the pathological conditions and vascular risk factors that may precipitate VaDep, particularly in relation to stroke and cerebral small-vessel disease. VaDep is distinguished by unique pathophysiological mechanisms and treatment responses. We categorize these mechanisms into three groups: 1) macroscopic mechanisms, including vascular aging, cerebral hypoperfusion, blood-brain barrier disruption, and neural circuit dysfunction; 2) microscopic mechanisms, involving the inflammatory response, hypothalamic-pituitary-adrenal axis dysregulation, impaired monoamine synthesis, and mitochondrial dysfunction; and 3) undetermined mechanisms, such as microbiota-gut-brain axis dysbiosis. These insights support VaDep as a distinct depression subtype, differentiating it from late-life depression and major depressive disorder. Treatment is challenging, as patients with VaDep often exhibit resistance to conventional antidepressants. Addressing vascular risk factors and protecting vascular integrity are essential for effective management. Future research should validate these mechanisms and develop novel diagnostic and therapeutic approaches to improve VaDep outcomes.

BackgroundDepressive comorbidity in neurodegeneration has been shown to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, its pathophysiology is not completely understood.ObjectiveHere, we characterize aberrant functional resting state networks (RSNs) characterizing depressive comorbidity in both AD and MCI.MethodsWe conducted a systematic literature review on Scopus, PubMed, and Web of Science to extract experiments that compared resting state scans of depressed and non-depressed MCI or AD patients. We employed Activation Likelihood Estimation (ALE) meta-analysis on eligible studies resulting from the search, to describe regions of significant co-activation across studies.ResultsThe systematic search resulted in 17 experiments, with 303 participants in total. The ALE yielded 10 clusters of significant co-activation distributed in the five major RSNs and across cortico-basal ganglia-thalamic circuits.ConclusionsDepressive comorbidity in neurodegeneration presents signature aberrant resting-state fluctuations. Understanding these within- and between-network alterations may be useful for future diagnostic and therapeutic applications.

ObjectiveChanges in angiogenesis have been shown to contribute to cognitive decline and dementia. We aimed to identify angiogenesis blood markers associated with cognitive performance in older adults with mild cognitive impairment (MCI), remitted major depressive disorder (rMDD), or both (rMDD + MCI) who are at risk for dementia.MethodWe analyzed data from participants with MCI, rMDD, or rMDD + MCI in the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression study. Elastic net regression was used to select variables associated with cognitive performance among 19 angiogenesis markers and 6 covariates. Linear regressions were used to determine which of the selected angiogenesis markers were associated with cognitive performance, controlling for the selected covariates. Significant angiogenesis markers were independently analyzed without other angiogenesis markers, controlling for covariates, with subgroup analyses in those with and without rMDD.ResultsAngiogenin was the only selected marker associated with cognitive performance (β = 0.28, Padj = 0.03, f² = .02) when controlling for other selected markers (endothelial cell-specific molecule 1, e-selectin, interleukin-33 [IL-33], oncostatin M, platelet-derived growth factor-AB, IL-33 receptor, and tissue inhibitor of metalloproteinases-1) and selected covariates (age, education, apolipoprotein E ε4 status, diagnosis, and cardiovascular risk factors). When independently analyzed, angiogenin remained positively associated with cognitive performance (β = 0.21, P = 0.01, f² =.02), controlling for the covariates. In subgroup analyses, angiogenin was also associated with cognition in rMDD and rMDD + MCI participants (β =0.50, SE = 0.14, P < 0.001, f² = 0.08) and in MCI-only participants (β= 0.20, SE = 0.09, P = 0.02, f² = 0.02).ConclusionThe association of angiogenin with cognitive performance highlights a potentially novel biological pathway that could influence cognition in older adults at risk for dementia. Angiogenin may protect against cognitive decline, opening new avenues for innovative preventive, or therapeutic interventions.

White matter hyperintensities (WMHs) are associated with late-life depression (LLD) and are considered a hallmark of MRI-defined vascular depression. However, their impact on depression recurrence in LLD is less well known.

We investigated this relationship using data from a 2-year multi-site, longitudinal study, where baseline WMH volumes were obtained using 3 T FLAIR magnetic resonance imaging (MRI) from 145 participants, of which 102 had remitted LLD and 43 were control participants. We analyzed the effect of baseline WMH volume on LLD relapse over 2 years using regression and adjusting for total intracranial volume, age, sex, race, education, and study site. We performed survival analyses using a Cox proportional hazard model to determine whether baseline WMH volume was associated with time to relapse in LLD.

We found that participants with LLD had greater WMH volume at baseline than control participants, but not if accounting for peripheral cardiovascular disease. Participants with LLD who relapsed within 8 months of baseline had larger WMH volume than control participants but did not statistically differ from those that remained remitted; this effect was lost when expanding to participants that relapsed at any point in the 2-year study. WMH burden was not associated with time to relapse, suggesting greater WMH volumes are not indicative of faster relapse rates in LLD.

Our results show that WMH burden may play a role in the early - but not the delayed - relapse of LLD, and they underscore the intricate dynamic of the biological markers underlying LLD treatment response and relapse.

To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

A retrospective cohort study.

A population-based study using the Texas Medicare data.

11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, had consistent diabetes medication intake, were not diagnosed with depression or prescribed antidepressants during the 2-year look-back period and received regular care from Medicare providers.

The main outcome was a new episode of depression, identified by a new depression diagnosis during the follow-up period.

A total of 59 057 T2D patients (mean (SD) age, 75.4 (6.4) years; 30 798 (52.1%) female) were followed up to 96 months. Of these, 22.5% patients had a new episode of depression at the 5-year follow-up. Compared with the metformin-only group, patients in the non-metformin-containing regimens had a higher risk of new episode depression (HR: 1.17, 95% CI 1.05 to 1.30 for DPP4i-only; HR: 1.06, 95% CI 1.01 to 1.12 for SU-only), but there was no significant difference among patients receiving metformin-containing combination therapy. Metformin/TZD and metformin/SU/DPP4i combination treatments had a lower risk of new episodes of depression than metformin-only (HR: 0.88, 95% CI 0.78 to 0.99 and HR: 0.83, 95% CI 0.71 to 0.98 separately). The same direction of association was observed in sensitivity analyses.

This retrospective cohort study found that T2D patients treated with metformin/TZD and metformin/SU/DPP4i had the lowest risk of new episodes of depression. These findings suggest that certain combinations of metformin with other antidiabetic medications may be associated with a reduced risk of new-onset depression. Therefore, it could be beneficial to incorporate depression risk evaluation into routine diabetes care and consider it in the decision-making process for diabetes medication types, especially when deprescribing metformin.

A substantial body of evidence indicates that stroke is a primary cause of death and disability on a global scale. The presence of post-stroke depression has been demonstrated to exert a substantial influence on the prognosis of stroke patients, underscoring the imperative for the identification and early prevention of post-stroke depression. The objective of this study was to examine the association between cardiac history and post-stroke depression (PSD) in Chinese stroke patients, with the aim of identifying high-risk groups, promoting early intervention strategies, and enhancing patient prognosis. This study was based on data from the 2020 China Health and Retirement Longitudinal Study (CHARLS), which included 933 respondents with a history of stroke. Univariate and multivariate logistic regression analyses were used to assess the effects of cardiac history and other variables on post-stroke depression (PSD). The results indicated a correlation between cardiac history and post-stroke depression (PSD). In addition, the data showed that gender, activities of daily living (ADLs), cognitive functioning, and life satisfaction also had an effect on post-stroke depression (PSD). The findings presented here indicate that patients with a history of cardiac disease are more likely to develop post-stroke depression. This provides valuable insights into the clinical management of stroke patients and the prevention of post-stroke depression. The emotional health assessment of such patients should be emphasized in clinical management, and appropriate psychological support and interventions should be provided to improve their overall prognosis.

Late-life depression (LLD) is associated with white matter (WM) alterations. Current evidence indicates amyloid PET tracers as sensitive and reliable markers for evaluating normal-appearing WM (NAWM) on magnetic resonance imaging (MRI), showing an association between lower uptake and Alzheimer's disease pathology and higher uptake with age-related changes. Utilizing this novel and reliable technique, we aimed to distinguish two hypothetical models for neurobiology of LLD: the pathological neurodegenerative model and the accelerated aging model.

In this monocentric cross-sectional study, a total of 103 participants, including 61 patients with LLD (age 73.8±7.0 years, 41 female) and 42 healthy controls (age 72.5±7.6 years, 28 female), underwent PET imaging with 18F-flutemetamol, MRI, and clinical assessment. T2-weighted fluid-attenuated inversion recovery (FLAIR) images were segmented into WM hyperintensities (WMH) and NAWM.

18F-flutemetamol standardized uptake value ratio (SUVR) in WMH was significantly lower than that in NAWM (t=7.8, df=102, p<0.001). Compared to healthy controls, patients with LLD exhibited higher 18F-flutemetamol SUVR in both NAWM (p<0.001, Cohen's d=0.91) and WMH (p=0.005, d=0.56), even after controlling for age and 18F-flutemetamol SUVR in cortical gray matter.

Our result of elevated 18F-flutemetamol uptake in NAWM does not align with the pathological neurodegenerative aging pattern observed in Alzheimer's disease but is in line with patterns of age-related changes. This distinction is crucial for the development of future targeted treatments.

Depressive symptoms are prevalent among those aged 90 and above, the oldest old, but studies examining associations with neuroimaging markers of brain health are sparse. Therefore, we tested the association between depressive symptoms and neuroimaging outcomes, and assessed whether these associations differ by gender. This cross-sectional study used data from 225 participants with imaging data from the LifeAfter90 study (mean [SD] age=93.1 [2.2] years, 56 % female, 22 % African American/Black, 25 % Asian, 18 % Hispanic/Latino, 28 % White, 7 % multiracial/other). Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS), and neuroimaging markers were collected via 3T magnetic resonance imaging and amyloid positron emission tomography (PET) scans. Average GDS score was 2.6 ± 2.3. Greater GDS scores were associated with lower total (β=-0.06; 95 % CI -0.12,>-0.01; p = 0.04) and right (β=-0.07; 95 % CI -0.13,-0.01; p = 0.02) hippocampal volumes. While GDS-by-gender interactions were not significant (p's interaction>0.05), estimates of GDS with lower total and right hippocampal volume were stronger among women compared with men in gender-stratified models. GDS was not associated with other measures of cortical volume, amyloid PET, nor white matter integrity. In a racially and ethnically diverse cohort, greater depressive symptoms were cross-sectionally associated with lower hippocampal volume among participants aged 90+.

Recent evidence from clinical and animal studies with anti-inflammatory agents in depression is conflicting. One possible reason is the heterogeneity of baseline inflammation levels. Since older adults are generally associated with chronic low-grade inflammation and depression is one of the most common mental disorders in this population, this meta-analysis aimed to evaluate the therapeutic and preventative effects of anti-inflammatory interventions for depression among older adults. PubMed, Cochrane Library, Embase, and PsycINFO were searched for randomized controlled trials (RCTs) up to November 18, 2024. The primary outcomes were mean change scores of depression scores and incidences of depression after treatment. Pooled standard mean differences (SMDs) and odds ratios (ORs) including 95% confidence intervals (95% CI) were calculated. Of 3116 screened articles, 31 RCTs met the inclusion criteria, with 25 studies investigating efficacy and 7 studies investigating the incidence following anti-inflammatory treatment. Anti-inflammatory interventions were statistically significantly more effective than placebo in reducing depressive scores for older adults with depression (SMD = -0.57, 95% CI = -0.98 to -0.15, p = 0.008). Sub-group analyses supported the use of omega-3 fatty acids (SMD = -0.14, 95% CI = -0.27 to -0.02, p = 0.03) and botanical drug or dietary intervention (SMD = -0.86, 95% CI = -1.58 to -0.13, p = 0.02) among older participants. While limited by substantial heterogeneity among included studies, these results reveal the moderate beneficial effects of anti-inflammatory interventions for the treatment and prevention of depression among older adults. Future high-quality RCTs are warranted to determine which anti-inflammatory interventions are most preferential for older patients with depression.

Depression is a serious health problem worldwide and is often associated with disability and reduced quality of life. In aging societies, early recognition of depression in older adults is highly relevant. Therefore, this study investigated the prevalence of depressive symptoms in individuals aged 50 and older with the aim to identify those at risk for major depression.

We performed a retrospective cross-sectional study with data from 1000BRAINS to assess depressive symptoms in a sample of 1017 healthy adults aged 50 and older. The prevalence and dimension of depressive symptoms were measured by the Beck Depression Inventory II, and differences between demographic, clinical, and lifestyle-associated variables and the prevalence of depressive symptoms were analyzed.

Depressive symptoms were present in 21.3 % of the participants and were minimal in 14.2 %, mild in 4.5 %, moderate in 1.8 %, and severe in 0.8 %. The prevalence of depressive symptoms was highest in the age group 50 to 59 years, and the prevalence of severe depressive symptoms decreased with increasing age. A positive family history of depression, cognitive impairment, medication intake, and polyneuropathy were associated with significantly higher levels of depressive symptoms.

The retrospective cross-sectional design and evaluation of depressive symptoms by a self-rating instrument may limit the generalizability of the results.

This study supports earlier findings of a higher prevalence of depressive symptoms among older adults. The group aged 50 to 59 appears to be particularly affected. Additionally, poor physical health, greater cognitive impairment, and sex-specific factors appear to contribute to depressive symptomatology.

Previous observational studies showed associations between obstructive sleep apnea (OSA) and depression and other negative moods. However, the causality has not been determined. Single nucleotide polymorphisms were identified as instrumental variables by screening from genome-wide association studies. Bidirectional two-sample mendelian randomization (MR) was applied to assess the potential causal relationship between OSA and depression, subjective well-being, negative moods. Inverse variance weighting (IVW) method and weight median were chosen as the main methods to estimate possible causal effects. MR-Egger, MR pleiotropy residual sum and outlier and leave-one-out analysis methods, were used as sensitivity analysis methods to ensure robust results. MR analyses indicated significantly causal association of OSA on depression (OR = 1.22, P = .010) and major depressive disorder (OR = 1.02, P = .006). Furthermore, genetically predicted OSA was negatively associated with subjective well-being (βIVW = -0.06, P = .009), and was positively associated with negative moods including depressed affect (OR = 1.04, P = .012), irritable mood (P = .006), feeling lonely (P = .011), feeling fed-up (P = .005) and mood swings (P = .017). There is no reverse effect of the above psychiatric traits on OSA. Genetic predisposition to OSA causally increased depression and major depressive disorder. Consistently, OSA has causal impacts on both subjective well-being, representing positive emotions, and negative moods.

The purpose of this investigation was to verify the association between mental health (MH) indicators with walking capacity in patients with PAD.

Two hundred and forty-six patients with PAD and claudication symptoms participated in this study. Physical function was assessed objectively with the 6-min walk test (6MWT) and subjectively using the Walking Impairment Questionnaire (WIQ). MH was assessed by the World Health Organization Quality of Life-Bref (WHOQOL-Bref) (six questions were selected - 1, 2, 10, 16, 19, and 26). Patients were divided into tertile groups according to their composite z-score for mental health (Low MH, Middle MH, and High MH).

The High MH group presented higher scores (p < 0.05) for the WIQ (distance = 26.8 ± 25.6, speed = 25.4 ± 17.3, and stairs = 33.6 ± 27.5), claudication onset distance (161.6 ± 83.6 m), and total walking distance (352.9 ± 79.6 m) compared to Low MH (WIQ distance = 14.8 ± 16.2, 17.7 ± 13.0, and stairs = 22.7 ± 20.7). Additionally, the High MH group presented a longer claudication onset distance (115.5 ± 70.5 m), and total walking distance in 6MWT (306.6 ± 83.2 m), and higher scores in the total walking distance compared to Middle MH (309.5 ± 93.6 m) (p < 0.05).

In patients with PAD, MH was positively associated with walking capacity. Based on these results, treatments that can improve mental health, through different mechanisms, can also positively influence the ability of these patients to walk.

Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia.

Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.

Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.

In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.

Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Inflammation is a leading biological risk factor contributing to unfavorable outcomes of major depressive disorder (MDD). Both inflammation and depression are associated with similar alterations in brain structure, indicating that brain structural alterations could serve as a mediating factor in the adverse influence of inflammation on clinical outcomes in MDD. Nonetheless, longitudinal research has yet to confirm this hypothesis. Therefore, this study aimed at elucidating the relationships between peripheral inflammatory cytokines, gray matter volume (GMV) alterations, and antidepressant response in MDD. We studied 104 MDD patients treated with selective serotonin reuptake inhibitors and 85 healthy controls (HCs). Antidepressant response was assessed after 8-week antidepressant treatment by changes in 17-item Hamilton Depression Rating Scale (HAMD-17) scores. The GMV alterations were investigated using a voxel-based morphometry analysis. Inflammatory cytokines were measured using flow cytometry. Partial correlations were used to explore the relationships between inflammatory cytokines, GMV alterations, and antidepressant response. Compared to HCs, MDD patients showed reduced GMVs primarily in the frontal-limbic area, right insula, and right superior temporal gyrus. Furthermore, the alterations in GMVs, particularly in the right middle frontal gyrus and the left anterior cingulate gyrus, were associated with ΔHAMD-17 and inflammatory cytokines. Additionally, GMV alterations in the right middle frontal gyrus mediated the negative relationship between interleukin -1β and ΔHAMD-17. This study contributes to understanding the effect of inflammation on the brain and their relationships with antidepressant response, offering a potential explanation for the connection between inflammatory status and treatment efficacy.

Physical activity could be associated with psychological symptoms in young people with major depressive disorder (MDD). Using actigraphy and ecological momentary assessment (EMA), we investigated the associations between physical activity and stress, anxiety and positive and negative affect in young people with MDD.

Actigraphy and EMA were collected daily in 40 young participants (aged 16-25 years) with MDD over 8 weeks. Multi-level linear mixed models were used to examine within- and between-person daily associations between physical activity and symptoms of stress, depression and positive and negative affect.

Participants with at least 14 days of complete data were included in the analysis (n participants = 22; total days = 598). Typical (defined as average across the assessment period) vigorous physical activity was significantly associated with lower daily stress (β[95% CI] = -0.152 [-0.298, -0.007], p = 0.041) and higher daily positive affect (0.526 [0.061, 0.992], p = 0.028). Variability in daily light (0.004 [0.001, 0.006], p = 0.010) and moderate physical activity (0.004 [0.001, 0.007], p = 0.009) were positively associated with daily stress. Variability in daily light (0.003 [0.001, 0.006], p = 0.018) and moderate physical activity (0.004 [0.001, 0.007], p = 0.011) were positively associated with daily anxiety.

Various intensities of daily physical activities were associated with symptoms of stress, anxiety and positive affect in young people with MDD. Future research on larger samples should validate the causal and daily associations between physical activity and psychological symptoms to promote evidence-based behavioural strategies to improve psychological symptoms in young people with MDD.

The goal of this paper is to introduce the hypothesis that white matter (WM) and vascular injury are long-term consequences of repetitive head impacts (RHI) that result in a novel T2 fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging pattern. A non-systematic literature review of autopsy and FLAIR studies of RHI-exposed adults was first conducted as a foundation for our hypothesis. A case series of RHI-exposed participants is presented to illustrate the unique FLAIR WM hyperintensities (WMH) pattern. Current literature shows a direct link between RHI and later-life WM/vascular neuropathologies, and that FLAIR WMH are associated with RHI, independent of modifiable vascular risk factors. Initial observations suggest a distinctive pattern of WMH in RHI-exposed participants, termed RHI-associated WMH (RHI-WMH). RHI-WMH defining features are as follows: (1) small, punctate, non-confluent, (2) spherical, and (3) proximal to the gray matter. Our hypothesis serves as a call for research to empirically validate RHI-WMH and clarify their biological and clinical correlates. HIGHLIGHTS: Repetitive head impacts (RHI) have been associated with later-life white matter (WM) and vascular neuropathologies. T2 FLAIR MRI of RHI-exposed participants reveals a potentially unique WM hyperintensity (WMH) pattern that is termed RHI-associated WMH (RHI-WMH). RHI-WMH are characterized as (1) small, punctate, and non-confluent, (2) spherical, and (3) proximal to the gray matter at an area anatomically susceptible to impact injury, such as the depths of the cortical sulci.

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.

Somatic symptom disorder (SSD) exacerbates subjective cognitive decline (SCD). This association can be significantly impacted by the mental well-being of the SSD patients. However, the underlying mechanisms remain obscure.

A total of 525 elderly patients, who visited the Department of Neurology of Fujian Medical University Union Hospital between October 2017 and August 2024, and the Department of Neurology of Quanzhou First Hospital Affiliated to Fujian Medical University between August 2022 and August 2024, were included in the study. Data of sociodemographics, medical history, somatic symptom disorder, subjective cognitive decline, depression, and anxiety were analyzed by simple, serial and moderated mediation models to evaluate the impact of depression and anxiety on the linkage between SSD and SCD.

SSD significantly affected SCD. Simple mediation analysis showed that depression and anxiety significantly mediated the association between SSD and SCD (βdepression = 0.079, 95% CI: 0.030 to 0.132; βanxiety = 0.058, 95% CI: 0.031 to 0.093). Serial mediation analyses indicated that the worsening of SSD exacerbates anxiety, in turn aggravating depressive symptoms and SCD (β b  = 0.044, 95% CI: 0.026 to 0.069). Moderated mediation model revealed that the depressive symptoms-conferred mediation of the correlation between SSD and SCD was moderated by anxiety symptoms (β = -0.073, 95% CI: -0.131 to -0.014).

These findings provided new insights into possible avenues for prevention and intervention of SCD through SSD-based treatments with a multifaceted approach to psychiatric disorders.

Late-life depression (LLD) is characterized by medial temporal lobe (MTL) abnormalities. Although gray matter (GM) and white matter (WM) differences in LLD have been reported, few studies have investigated them concurrently. Moreover, the impact of aetiological factors, such as neurodegenerative and cerebrovascular burden, on tissue differences remains elusive.

This prospective cross-sectional study involved 72 participants, including 33 patients with LLD (mean age 72.2 years, 23 female) and 39 healthy controls (HCs) (mean age 70.6 years, 24 female), who underwent clinical and positron emission tomography (PET)-magnetic resonance imaging (MRI) assessments. High-resolution 3D T1-weighted and T2-weighted FLAIR images were used to assess MTL GM volumes and white matter hyperintensities (WMHs), a proxy for cerebrovascular burden. Diffusion kurtosis imaging metrics derived from multishell diffusion MRI data were analyzed to assess WM microstructure in the following MTL bundles reconstructed using constrained spherical deconvolution tractography: uncinate fasciculus, fornix, and cingulum. Standardized uptake value ratio of 18F-MK-6240 in the MTL was used to assess Alzheimer's disease (AD) type tau accumulation as a proxy for neurodegenerative burden.

Compared to HCs, patients with LLD showed significantly lower bilateral MTL volumes and WM microstructural differences primarily in the uncinate fasciculi bilaterally and right fornix. In patients with LLD, higher vascular burden, but not tau, was associated with lower MTL volume and more pronounced WM differences.

LLD was associated with both GM and WM differences in the MTL. Cerebrovascular disease, rather than AD type tau-mediated neurodegenerative processes, may contribute to brain tissue differences in LLD.

Motoric cognitive risk syndrome (MCRS) is a pre-dementia syndrome of growing interest, yet it remains understudied in Latin America with a significant lack of information on the interaction between its risk factors and race.

To estimate the prevalence of MCRS among older adults in Brazil, investigate its association with various clinical and sociodemographic variables, and explore the potential of effect modification by race.

This cross-sectional, population-based study was conducted among community-dwelling older adults in Brazil, with data collected between 2015 and 2016. The diagnosis of MCRS was established following the standard recommended by the original study that first described it. We used Poisson regression models to analyze the association between MCRS and a list of 21 variables identified from a systematic review.

A total of 4677 participants aged 60 years and older were included. The prevalence of MCRS in the Brazilian population of older adults was 4.34% (95% CI: 3.20%-5.48%). Higher levels of education and physical activity showed protective associations with MCRS, while depression and stroke demonstrated risk associations. A significant cross-over interaction between race and depression regarding MCRS was observed, such that the association of depression with MCRS was approximately three times higher among White individuals than Black individuals.

Our results challenge previous estimates that Latin America is the region with the highest prevalence of MCRS among older adults and signal the need for further studies to better investigate the modification of effect of the association between depression and MCRS by race.

Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.

Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.

A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

Late-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.

We 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.

We 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.

In 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.

Depression is a significant global health concern, projected to become the leading disease burden. Vascular burden has been implicated in the pathogenesis of depression. Conversely, whether depression independently influences the process of vascular aging is unknown. This study aims to investigate the mutual relationship between vascular age and depression.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study included 27,764 participants after exclusions. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Vascular aging was assessed by estimated pulse wave velocity (ePWV) and the heart age/vascular age (HVA) based on Framingham Risk Score (FRS). The study employed weighted logistic regression and Cox proportional hazards models to analyze the association between vascular age and depression as well as its mortality risk. Mendelian randomization was utilized to explore the causal associations.

Individuals with depression exhibited a higher risk of an advanced vascular age over their chronological age. Mendelian randomization analysis indicated a causal relationship between depression and arterial stiffness. A significant association was found between vascular age and depression incidence with odds ratios ranging from 1.10 to 1.38. As vascular age increased, the risk of mortality in individuals with depression increased by 22 % and 46 %, respectively.

The study design limits the exploration of the dynamic relationship between changes in vascular age and depression due to the single timepoint measurement.

This study highlights the bidirectional relationship between depression and vascular age. Vascular age is a significant biomarker for the risk and prognosis of depression, while depression may contribute to vascular aging, which underscores the importance of integrated strategies for managing both vascular health and depression.

Both metabolic syndrome (MetS) and cognitive dysfunction impair health-related quality of life (HRQOL). This study aims to determine whether individuals experiencing both MetS and cognitive dysfunction have lower HRQOL.

This cross-sectional study enrolled 567 participants who attended outpatient clinics at a medical center in northern Taiwan. MetS was diagnosed according to the modified criteria for the Asian population. Cognitive function was categorized as normal, mild cognitive dysfunction, and advanced cognitive dysfunction according to the score of the Montreal Cognitive Assessment, Taiwanese version. HRQOL was assessed using the SF-36v2® Health Survey (SF-36v2). The associations of the comorbidity status of MetS and cognitive dysfunction with HRQOL were analyzed using linear regression models, adjusting for age, sex, marital status, education level, income groups, and activities of daily living.

Out of 567 participants, 33 (5.8%) had MetS with mild cognitive dysfunction, and 34 (6.0%) had MetS with advanced cognitive dysfunction. Participants with both MetS and advanced cognitive dysfunction exhibited the lowest scores in the physical component summary and almost all scales of HRQOL. MetS exacerbated the inverse association between mild cognitive dysfunction and the mental component summary. For those with MetS, the scores on scales of role physical, bodily pain, vitality, and social functioning worsened as cognitive function deteriorated (all Ptrend<0.05).

As the severity of comorbidity between MetS and cognitive dysfunction varies, patients exhibited poorer performance in different aspects of HRQOL. Future research is needed to find solutions to improve HRQOL for patients with both MetS and cognitive dysfunction.

Post-stroke depression (PSD) is one of the most common and severe neuropsychological sequelae after stroke. Using a prediction model composed of multiple predictors may be more beneficial than verifying the predictive performance of any single predictor. The primary objective of this study was to construct practical prediction tools for PSD at discharge utilizing a decision tree (DT) algorithm.

A multi-center prospective cohort study was conducted from May 2018 to October 2019 and stroke patients within seven days of onset were consecutively recruited. The independent predictors of PSD at discharge were identified through multivariate logistic regression with backward elimination. Classification and regression tree (CART) algorithm was employed as the DT model's splitting method.

A total of 876 stroke patients who were discharged from the neurology departments of three large general Class A tertiary hospitals in Wuhan were eligible for analysis. Firstly, we divided these 876 patients into PSD and non-PSD groups, history of coronary heart disease (OR = 1.835; 95 % CI, 1.106-3.046; P = 0.019), length of hospital stay (OR = 1.040; 95 % CI, 1.013-1.069; P = 0.001), NIHSS score (OR = 1.124; 95 % CI, 1.052-1.201; P = 0.001), and Mini mental state examination (MMSE) score (OR = 0.935; 95 % CI, 0.893-0.978; P = 0.004) were significant predictors. The subgroup analysis results have shown that hemorrhagic stroke, history of hypertension and higher modified Rankin Scale score (mRS) score were associated with PSD at discharge in the young adult stroke patients.

Several predictors of PSD at discharge were identified and convenient DT models were constructed to facilitate clinical decision-making.

Late-onset depression (LOD) is often associated with more severe cognitive impairment and a higher risk of disability and suicide. Emerging evidence suggests that immune system problems may be involved. This study aims to systematically characterize the genetic signature of LOD based on the immune landscape.

The expression profile of GSE76826 was obtained from the Gene Expression Omnibus (GEO) database to gather gene expression data for 10 LOD patients and 12 healthy controls (HC). Various analyses, such as Single-Sample Gene Set Enrichment Analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), were used to mine key genes closely related to LOD. ImmuCellAI helped us understand differences in the immune environment between LOD patients and controls, and we used an LOD animal model to validate the relevant immune characteristics.

We found enriched immune pathways linked to LOD and adaptive immune responses. Using advanced bioinformatics techniques, we identified two key genes: apelin (APLN) and leptin (LEP), which have good diagnostic efficacy (AUC=0.925, 95% CI=1.00-0.83) for LOD. Neutrophil infiltration increased significantly in LOD, while CD8+ T lymphocytes (CD8_T) decreased. We finally constructed an animal model of LOD, validated two key genes and microglia marker genes in blood and hippocampus, and detected elevated pro-inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).

We identified and validated the presence of aberrant expression of APLN and LEP in LOD and described a possible immune mechanism involving increased release of IL-6 and TNF-α, leading to decreased CD8_T infiltration and increased neutrophil infiltration. Meanwhile, peripheral inflammation across the blood-brain barrier further promotes microglia activation, leading to neuronal damage.

Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health.

We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models.

The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001).

Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown.

Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P=0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P<0.001).

PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.