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OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Depression is a heterogeneous disorder, both in terms of patient symptomatology and in patient sociodemographic factors. Here, we examine the contribution of age to this heterogeneity, by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan. We analyzed data from the Cambridge Centre for Aging Neuroscience (Cam-CAN) cohort (N = 2591, age 18–99). A subset of this cohort (N = 647) underwent structural MRI. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Cognitive assessments were performed using The Addenbrooke's Cognitive Examination Revised. Generalized linear models were employed to examine the relationship between depressive symptoms and cognitive performance. Statistical parametric mapping explored age-dependent associations between depressive symptoms and grey matter volume. Cognitive performance was associated with a significant age by depression by cognitive domain interaction, indicating that older individuals with more depressive symptoms had a lower cognitive performance, particularly in the fluency domain. Structural MRI revealed preferential depression-related reduction in grey matter volume in the left and right hippocampi in older adults. By contrast, in younger adults, depressive symptoms were more strongly associated with grey matter volume reduction in the left superior frontal gyrus and left middle frontal gyrus. Collectively, these findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the pathophysiological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan. • Older individuals with more depressive symptoms have a lower cognitive performance. • This effect is significantly stronger for fluency domain. • Depressive symptoms are associated with different brain regions across the lifespan. • Depressive symptoms in older adults are associated with reduced hippocampal volume. • Depressive symptoms in young adults are associated with reduced frontal volume. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? This study investigated if tau accumulation is higher in late life depression (LLD) than in a healthy comparison group and in patients with mild cognitive impairment due to Alzheimer's (MCI). • What is the main finding of this study? LLD patients exhibited lower gray matter volume than the comparison group in temporal regions but similar tau accumulation, in contrast to mild cognitive impairment due to Alzheimer's (MCI) patients who showed significantly higher tau burden. • What is the meaning of the finding? Alzheimer associated tau pathology is unlikely to contribute to lower gray matter volume in major depressive disorder in older adults. To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI). Monocentric, cross-sectional study. University Psychiatric hospital, memory clinic and outpatient neurology practice. A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging. PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively. Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD. Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives: While depression is associated with an increased risk of Alzheimer's dementia (AD), traditional AD-related biomarkers, such as amyloid-beta, have shown limited predictive value for late-life depression. Oxidative stress has emerged as a potential indicator given its shared role in both depression and dementia. This study investigated the longitudinal relationship between oxidative stress biomarkers and risk of dementia in patients with depression. Materials and Methods: A longitudinal cohort of 146 older patients with major depressive disorder was analyzed. Biomarkers, such as nitrotyrosine, protein carbonyl, F2-isoprostanes, malondialdehyde, 4-hydroxynonenal, and 8-hydroxy-2′-deoxyguanosine, were collected at baseline and measured using an enzyme-linked immunosorbent assay. AD conversion was determined using comprehensive neuropsychological assessment. Cox proportional hazards models were used to evaluate the association between oxidative stress biomarkers and AD conversion after adjusting for confounders. The log-rank test, using the minimum p-value approach, was applied to determine the optimal cut-off value for significantly associated biomarkers of AD-free survival rates. Results: During the follow-up period ranging from 1.00 to 18.53 years, 41 (28.08%) patients converted to AD. Nitrotyrosine showed a significant association with increased risk of AD (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00–1.01; p = 0.0045). For clinical applicability, patients with plasma nitrotyrosine levels ≥170 nM as the cut-off value had a 5.14-fold increased risk of AD (adjusted HR, 5.14; 95% CI, 2.02–13.07; p = 0.0006). Other biomarkers, such as protein carbonyl, F2-isoprostanes, malondialdehyde, 4-hydroxynonenal, and 8-hydroxy-2′-deoxyguanosine, were not significantly associated with AD conversion. Conclusions: Nitrotyrosine, a biomarker that reflects nitrosative damage, emerged as a significant predictor of dementia risk in older patients with depression, highlighting its potential as an early biomarker of dementia. Further validation of these results is required using a larger sample size. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the medication-related burden (MRB) of patients with late-life depression (LLD) and its influencing factors in China using the Living with Medicines Questionnaire-3 (LMQ-3), providing reference for reducing the MRB of those patients. Method: A cross-sectional study was conducted between September 2023 and January 2024 on 588 patients with LLD. LMQ-3 and MRB factors questionnaire were used for data collection. The distribution of variables was assessed using descriptive analysis, while analyses of Mann-Whitney and Kruskal-Wallis were performed to evaluate inter-group differences. To explore the MRB among patients with LLD and influencing factors, multiple linear regression analysis was performed. Results: The median (IQR) LMQ-3 score of 588 participants was 102 (18), indicating a moderate MRB level. Regression analysis revealed a significant trend toward higher perceived burden among patients aged 70–79 years old, living in rural areas, receiving more medical insurance settlements, using all cash, taking more than 5 drugs each time, and taking medicine more than 3 times a day (p < 0.05), which were risk factors for higher MRB. Conversely, patients who lived with their children, had an annual household income (including adult children) more than 50,000 Chinese Yuan, and no adverse drug reactions had lower LMQ-3 scores (p < 0.05), which were protective factors. Patients' concerns about medicine, their lack of autonomy in medicine regimens, and the lack of communication between patients and doctors on treatment regimens were the main causes of the burden. Conclusions: Results of this study provided preliminary evidence of the MRB among patients with LLD. Age, residence, living status, annual household income, type of drug payment, quantity and frequency of medication, and adverse reactions significantly affected the perceived medication burden. It is advisable for health policy makers and health care providers to implement appropriate intervention strategies and burden reduction programs for this vulnerable group. [ABSTRACT FROM AUTHOR]

Suicide 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. A 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. (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. The present study was a cross-sectional design. LLD-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. • LLD-S exhibited lower OI scores compared to LLD-NS and HOAs. • Interaction between SI and OI dysfunction contributed to lower information processing speed and visuospatial ability. • OI dysfunction mediated the differences in cognition between LLD-NS and LLD-S groups. • OI examination could be a valuable approach for identifying SI in LLD and screening for suicide risk. [ABSTRACT FROM AUTHOR]

The document delves into the intricate relationship between depression and Alzheimer's disease (AD), shedding light on the prevalence of depressive symptoms in AD patients and the potential risk factors and biological mechanisms connecting depression to AD. It also examines the impact of anti-amyloid drugs on depressive symptoms in AD patients, underscoring the necessity for further research to assess the effectiveness and safety of these treatments in individuals with depression. The text emphasizes the importance of closely monitoring the psychiatric symptoms of AD patients with mild to moderate depression who are undergoing anti-amyloid treatment, as well as the significance of early intervention and specialized assessment in managing depression to reduce the likelihood of developing associated comorbidities. [Extracted from the article]

Background: Late-life depression (LLD) has a poor response to the first-line standard antidepressant medications. This study aims to determine the effect of Vitamin B12 supplementation as an augmentation to the antidepressant medications as the first-line therapy in LLD to accelerate and/or maximize the response and remission. Materials and Methods: It was a prospective randomized controlled trial of 4 weeks; 62 depressed older adults (age >50 years) with low but not below the normal range of serum Vitamin B12 levels (>187 but

Abstract Background As global aging accelerates, depression among the elderly becomes more common. Research had revealed that patients with late-life depression (LLD) face a higher risk of suicide compared to their counterparts in other age groups, with the pathways to suicide being multifaceted. Thus, investigating the various factors linked to the elevated risk of suicide in patients with LLD is critical. Objective To investigate the factors associated with a high level of suicide risk among patients with LLD. Methods A total of 108 patients with LLD were recruited for this study. From October 2022 to November 2023, a cross-sectional study was conducted on patients with LLD from the Affiliated Brain Hospital of Guangzhou Medical University. Suicide risk was evaluated using the Chinese version of the Nurses’ Global Assessment of Suicide Risk Scale (NGASR). Potential influencing factors were included and analyzed through multivariate linear regression to identify the factors associated with a high level of suicide risk among patients with LLD. Results The mean NGASR score among patients with LLD was 7.30 ± 4.34 (range: 0 ~ 19). Multiple linear regression analyses revealed that depression-anxiety of the Brief Psychiatric Rating Scale (BPRS) (β = 0.31, 95% CI = 0.13, 0.45, p

Abstract Background Although 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. Methods Forty 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. Results There 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. Conclusions These 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.

Background: As global aging accelerates, depression among the elderly becomes more common. Research had revealed that patients with late-life depression (LLD) face a higher risk of suicide compared to their counterparts in other age groups, with the pathways to suicide being multifaceted. Thus, investigating the various factors linked to the elevated risk of suicide in patients with LLD is critical. Objective: To investigate the factors associated with a high level of suicide risk among patients with LLD. Methods: A total of 108 patients with LLD were recruited for this study. From October 2022 to November 2023, a cross-sectional study was conducted on patients with LLD from the Affiliated Brain Hospital of Guangzhou Medical University. Suicide risk was evaluated using the Chinese version of the Nurses' Global Assessment of Suicide Risk Scale (NGASR). Potential influencing factors were included and analyzed through multivariate linear regression to identify the factors associated with a high level of suicide risk among patients with LLD. Results: The mean NGASR score among patients with LLD was 7.30 ± 4.34 (range: 0 ~ 19). Multiple linear regression analyses revealed that depression-anxiety of the Brief Psychiatric Rating Scale (BPRS) (β = 0.31, 95% CI = 0.13, 0.45, p<0.001), activation of the BPRS (β=-0.29, 95% CI=-1.22, -0.35, p<0.001), normal cognitive function of the Mini-Mental State Examination (MMSE) (β = 0.21, 95% CI = 0.50, 3.48, p<0.05), involuntary admission (β = 0.20, 95% CI = 0.44, 3.43, p<0.05), and objective support of the Social Support Rating Scale (SSRS) (β = 0.21, 95% CI = 0.08, 0.66, p<0.05) were statistically associated with a high level of suicide risk in patients with LLD. Conclusion: This study found that LLD patients with severe depression-anxiety, low activation, normal cognitive function, involuntary admission, and strong objective support exhibited a high level of suicide risk. These patients should receive intensified monitoring and comprehensive measures should be implemented to prevent the occurrence of suicidal behaviors during hospitalization. [ABSTRACT FROM AUTHOR]

Background Late-life depression (LLD) predisposes individuals to cognitive decline, often leading to misdiagnoses as mild cognitive impairment (MCI). Voxel-based morphometry (VBM) can distinguish the profiles of these disorders according to gray matter (GM) volumes. We integrated findings from previous VBM studies for comparative analysis and extended the research into molecular profiles to facilitate inspection and intervention. Methods We comprehensively searched PubMed and Web of Science for VBM studies that compared LLD and MCI cases with matched healthy controls (HCs) from inception to 31st December 2023. We included 13 studies on LLD (414 LLDs, 350 HCs) and 50 on MCI (1878 MCIs, 2046 HCs). Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) was used for voxel-based meta-analysis to assess GM atrophy, spatially correlated with neuropsychological profiles. We then used multimodal and linear-model analysis to assess the similarities and differences in GM volumetric changing patterns. Partial least squares (PLS) regression and gene enrichment were employed for transcription-neuroimaging associations. Results GM volumes in the left hippocampus and right parahippocampal gyrus are more affected in MCI, along with memory impairment. MCI was spatially correlated with a more extensive reduction in the levels of neurotransmitters and a severe downregulation of genes related to cellular potassium ion transport and metal ion transmembrane transporter activity. Conclusion Compared to LLD, MCI exhibited more GM atrophy in the hippocampus and parahippocampal gyrus and lower gene expression of ion transmembrane transport. Our findings provided imaging-transcriptomic-genetic integrative profiles for differential diagnosis and precise intervention between LLD and MCI. [ABSTRACT FROM AUTHOR]

Late-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. This 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. A 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. The 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. The 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. • Improved Depressive Symptoms: Buspirone and venlafaxine combination improved depressive symptoms by the fourth week in elderly patients. • Enhanced Cognitive Function: Combination therapy enhanced cognitive function, particularly in visuospatial abilities, executive functions, attention, and memory, as shown by MoCA scores. • Variable Impact on Anxiety: Mixed results on anxiety: PP analysis showed improvement, while ITT analysis did not confirm significant changes. • Safety Profile: The therapy was well-tolerated with mild side effects, supporting its clinical use in elderly depression patients. • Need for Long-Term Evaluation : Additional research is needed to evaluate the therapy's long-term effects, particularly on anxiety. [ABSTRACT FROM AUTHOR]

Introduction: Late life depression (LLD) is characterized by specific clinical features including a high frequency of vascular form and frequent antidepressant treatment resistance. The expression and functions of the serine protease inhibitor, Plasminogen Activator Inhibitor‐1 (PAI‐1) is known to be altered by aging, vascular damage, insulin levels associated with a sedentary lifestyle, chronic stress leading to hypercortisolemia, and inflammatory changes linked to stress responses. These phenomena would be implicated in LLD like vascular depression. This article thus aims to review the existing literature regarding the association between LLD and plasmatic levels of PAI‐1, a marker of hypofibrinolysis. We hypothesize that increased age would be associated with changes in PAI‐1 plasma level and function which influence LLD pathogenesis and its treatment. Results: Although a large number of studies on PAI‐1 changes in the elderly exist, studies about its implications in LLD are sparse. Despite heterogeneous findings regarding the direction of variation in plasmatic PAI‐1 levels among elderly participants with LLD, all studies demonstrated an association between PAI‐1 levels and current or remitted depressive symptoms. Moreover, disruptions in the concentrations of other biological markers influencing PAI‐1 expression, such as cytokines or adipokines, were also observed, notably an increase in the levels of interleukins 6 and 8. Discussion: LLD genesis appears to be influenced by PAI‐1 regulatory loops which are implicated in senescence or cell death. The resistance to antidepressant treatment appears to be linked to distinct biological profiles involving inflammatory and fibrinolytic factors. Taken together these data suggest that PAI‐1 pathway may be a promising target of treatment development efforts for LLD, and depression in general. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Does childhood maltreatment affect the psychological treatment outcomes in late-life depression? • What is the main finding of this study? In older individuals with depression and childhood maltreatment, both specific and non-specific psychotherapy equally reduce depressive symptoms. However, in patients without childhood maltreatment, cognitive behavioral therapy for late-life-depression demonstrates greater efficacy over non-specific supportive psychotherapy. • What is the meaning of the finding? Practioners should consider a history of early trauma in their choice between specific and non-specific interventions. This is the first interventional study to assess the impact of childhood maltreatment (CM) on psychological treatment outcomes in patients with late-life depression (LLD). This is a secondary analysis of a multicenter, randomized controlled trial with 251 participants aged ≥60 years with moderate to severe depression. Participants were randomly assigned to cognitive behavioral therapy for late life depression (LLD-CBT) or to a supportive intervention (SUI). Treatment outcomes were measured by changes in the Geriatric Depression Scale (GDS). In the intention-to-treat sample (n = 229), both LLD-CBT (n = 115) and SUI (n = 114) significantly reduced depressive symptoms in patients with CM, with large effects at post-treatment (d = 0.95 [95% CI: 0.65 to 1.25] in LLD-CBT; d = 0.82 [95% CI: 0.52 to 1.12] in SUI). A significant treatment group*CM interaction (F (1,201.31) = 4.71; p =.031) indicated greater depressive symptom reduction in LLD-CBT compared to SUI at week 5 and post-treatment for patients without CM, but not at 6-month follow-up. Across both treatments, higher severity of the CM subtype 'physical neglect' was associated with a smaller depressive symptom reduction (F (1,207.16) = 5.37; p =.021). Specific and non-specific psychotherapy effectively reduced depressive symptoms in older individuals with depression and early trauma. For patients without early trauma, LLD-CBT may be preferable over SUI. Considering early trauma subtypes may contribute to develop personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Objectives: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. Participants and Measurements: Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical A β standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. Results: Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p =.031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p =.016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p =.010), but not OFC volume, remained significantly associated with anxiety. Conclusions: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions. [ABSTRACT FROM AUTHOR]

Background: Although 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. Methods: Forty 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. Results: There 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. Conclusions: These 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. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)—mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition. [Display omitted] • Astudy of mild cognitive impairment, late-life depression, and healthy controls. • We examined beta-amyloid (Aβ) and neurometabolites using PET and 7 T MRS. • We report novel associations between brain metabolites and Aβ. • Glu + Aβ predicts verbal learning scores better than Aβ-only models. [ABSTRACT FROM AUTHOR]

Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD. Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers. Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = −0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F (83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = −0.335, p = 0.002). No other associations were found. Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center. Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future. • Depressed older adults exhibited higher estimated deletion rate in mitochondrial DNA within exosomes (EX-mtDNA). • EX-mtDNA instability, marker of impaired mitochondrial function, may heighten susceptibility to adverse health outcomes. • The EX-mtDNA instability holds potential as indicator of inflammation status and cognitive outcomes in late-life depression. [ABSTRACT FROM AUTHOR]

Aim: 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. Methods: 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. Results: 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. Conclusions: 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; 24: 1022–1029. [ABSTRACT FROM AUTHOR]

Background: Depression and dementia are known to be associated. The identification of characteristics distinguishing depression prodromal to dementia from other depressive symptoms would be of value for early identification of dementia. The study of risk factors for depressive symptoms prodromal to dementia could improve preventive care and provide clues to the causes of dementia. Method: Dementia‐free 82‐year‐old participants were stratified into groups that did (n = 126) and did not (n = 378) subsequently develop dementia. Examinations took place from 2003 to 2005 and follow‐up ended 1 January 2015. Their baseline characteristics and depressive symptoms, measured using the 15‐item Geriatric Depression Scale (GDS‐15), were compared. Multivariate regression analyses were performed for the two groups separately, with the total GDS‐15 score as the dependent variable. Results: The groups did not differ significantly in answers to any of the GDS‐15 questions, or mean ± SD score, which was 2.4 ± 2.5 among those who developed dementia and 2.1 ± 2.3 among those who did not. (p = 0.33). Stroke before the age of 82 years and the inability to use stairs had significant impacts on the GDS‐15 scores in both groups. For those who did not develop dementia, age, dependence in activities of daily living, and cancer also had significant impacts. Cancer had opposite associations with depressive symptoms in the two groups. Conclusions: No difference was found in depressive symptoms preceding and not preceding dementia using the GDS‐15. The results suggest that risk factors for depressive symptoms may differ depending on whether they precede dementia. [ABSTRACT FROM AUTHOR]

Objectives: Mental and cognitive health is crucial to ensure well-being in older age. However, prolonged periods of stress, grief, and bereavement might compromise mental health balance, leading to profound changes. This study investigated the sex-stratified associations between midlife bereavement experiences (e.g. sibling loss, spousal loss, and multiple losses) and late-life depression (LLD) and cognitive impairment. Method: Linked data from the Swedish Level-of-Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD) were used. Multiple logistic regressions were performed to examine the associations between midlife bereavement and LLD (n = 1078) and cognitive impairment (n = 995), separately. Results: Sibling loss and multiple losses in midlife were associated with lower odds of LLD, especially among women. Among men, sibling loss in midlife was associated with lower odds of cognitive impairment, while the experience of two losses among women suggested an increased (but non-significant) risk of cognitive impairment. Interaction analyses did not show significant effects between bereavement and gender on LLD and cognitive impairment. Conclusion: Midlife bereavement might have gendered implications on LLD and cognitive impairment, but associations need to be confirmed by well-powered studies. Further research is warranted to elucidate the association between multiple midlife losses and reduced LLD risk. [ABSTRACT FROM AUTHOR]

Background: Elevated homocysteine levels and late‐life depression are risk factors for cognitive decline: a comparative study highlighted the association of late‐onset depression (LOD) with more significant cognitive deficits and brain pathology than early‐onset depression (EOD). Limited research has explored the possible interaction between homocysteine levels and their correlation with cognitive performance in patients with EOD and LOD. Methods: Fifty‐seven individuals with EOD, 56 with LOD, and 89 matched healthy controls (HC) were recruited. Global cognition, memory, execution, language, attention, visuospatial skills, and plasma homocysteine levels were examined. Results: Compared with HC and patients with EOD, patients with LOD had higher plasma homocysteine levels (p < 0.05), with no significant difference between HC and patients with EOD (p > 0.05). Furthermore, homocysteine levels and diagnosis groups showed significant main effects on depression and cognition, with no significant interaction effects being observed. Additionally, plasma homocysteine levels were negatively correlated with global cognition, attention, visuospatial skills, and executive function in patients with LOD (p < 0.05). Conclusions: Compared with HC and patients with EOD, elevated homocysteine levels in patients with LOD were independently associated with cognitive performance. The potential therapeutic efficacy of homocysteine‐lowering B‐vitamin supplementation could be explored as a viable intervention to mitigate the documented debilitating effects of cognitive deficits in this population. [ABSTRACT FROM AUTHOR]

Objectives: There is a large treatment gap for mental health conditions in sub‐Saharan Africa where most patients who receive any care do so from lay primary health care workers (PHCW). We sought to examine the experiences of PHCW who provide care for older people with depression in Nigerian primary health care (PHC) settings. Methods: Qualitative study design. A total of 24 PHCW participated. Using in‐depth key informant interviews (KIIs), we explored the views of 15 PHCW selected from 10 rural and urban PHCs in South‐Western Nigeria. An additional focus group discussion comprising nine participants was also conducted to discuss emerging themes from KIIs. Data were analysed using thematic analysis. Results: Three overall themes were identified: views about depression, treatment options, and community outreach implications. Participants perceived depression in older people as being characterised by a range of mood, behavioural, and cognitive symptoms which made clinical assessments particularly challenging. Common treatment options used by PHCW included general advice and counselling, as well as frequent need to prescribe mild analgesics, vitamins and occasional sedatives in line with patients' expectations. Antidepressants were rarely used even though PHCW are authorised. While home visits are part of their expected work schedule, PHCW rarely implemented these due to non‐availability of transport facilities. Mobile technology was identified as a possible way of overcoming this constraint to providing community based mental healthcare for older people. Conclusion: PHCWs perceived that patients' poor cognitive performance, expectations to prescribe sedatives, analgesics and vitamins, as well as non‐existence of community‐based services were existing barriers to providing evidenced based continued care for older people with depression in the study settings. [ABSTRACT FROM AUTHOR]

ABSTRACT Background In recent years, cognitive impairment has emerged as a pivotal symptom in elderly patients with depression, exerting a substantial impact on the course and prognosis of diseases. Moreover, it persists even following remission from depression during the rehabilitation period. However, there remains an incomplete understanding of the relevant influencing factors for cognitive impairment in elderly depressed patients, which seriously impedes the development of risk prediction models and the subsequent research on precision intervention programs. Objective The purpose of this study is to examine the current state of negative influencing factors and assessment tools for cognitive impairment in patients with late‐life depression (LLD), thereby providing a theoretical framework for the construction of subsequent targeted intervention programs. Methods The search strategy employed in this study followed an evidence‐based approach, utilizing a systematic scoping review to thoroughly explore six English and four Chinese databases up until November 2023. Two researchers independently conducted article screening and employed thematic analysis to categorize the results into themes. Results Following two rounds of rigorous screening conducted by the evidence‐based research team, data were meticulously extracted and succinctly summarized from five distinct themes encompassing socio‐demographic, physiological, psychological, genetic, and other related factors. In addition, a comprehensive compilation of 19 diverse assessment tools was undertaken. Ultimately, a total of 22 articles met the eligibility criteria for inclusion in this study. These comprised five longitudinal studies, nine pathological controlled studies, five cross‐sectional studies, two cohort studies, and one randomized controlled study. Conclusion Cognitive dysfunction is an important symptom of LLD, which seriously affects the survival of patients. At present, the research on its influencing factors mainly includes socio‐demographic, physiological, psychological, genetic, and other related factors. There have been existing cognitive function assessment tools specifically for those 18‐ to 65‐year‐old patients of major depressive disorder, but there is still a lack of reliability and validity tests in LLD.

Abstract Background The 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. Methods A 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. Results Over 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. Conclusion Economic 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.

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Background: The 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. Methods: A 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. Results: Over 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. Conclusion: Economic 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. [ABSTRACT FROM AUTHOR]

Background: The longitudinal course of late-life depression remains under-studied. Aims: To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns. Method: We analysed 15-year longitudinal data on 2745 dementia-free persons aged 60+ from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression (minor and major) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; subsyndromal depression (SSD) was operationalised as the presence of ≥2 symptoms without depression. Multistate survival models were used to map depression transitions, including death, and to examine the association of psychosocial (social network, connection and support), lifestyle (smoking, alcohol consumption and physical activity) and clinical (somatic disease count) factors with transition patterns. Results: Over the follow-up, 19.1% had ≥1 transitions across depressive states, while 6.5% had ≥2. Each additional somatic disease was associated with a higher hazard of progression from no depression (No Dep) to SSD (hazard ratio 1.09; 1.07–1.10) and depression (Dep) (hazard ratio 1.06; 1.04–1.08), but also with a lower recovery (HRSSD−No Dep 0.95; 0.93–0.97 [where 'HR' refers to 'hazard ratio']; HRDep−No Dep 0.96; 0.93–0.99). Physical activity was associated with an increased hazard of recovery to no depression from SSD (hazard ratio 1.49; 1.28–1.73) and depression (hazard ratio 1.20; 1.00–1.44), while a richer social network was associated with both higher recovery from (HRSSD−No Dep 1.44; 1.26–1.66; HRDep−No Dep 1.51; 1.34–1.71) and lower progression hazards to a worse depressive state (HRNo Dep−SSD 0.81; 0.70–0.94; HRNo Dep−Dep 0.58; 0.46–0.73; HRSSD−Dep 0.66; 0.44–0.98). Conclusions: Older people may present with heterogeneous depressive trajectories. Targeting the accumulation of somatic diseases and enhancing social interactions may be appropriate for both depression prevention and burden reduction, while promoting physical activity may primarily benefit recovery from depressive disorders. [ABSTRACT FROM AUTHOR]

The clinical phenotype of the so-called late-onset depression (LOD) affecting up to 30% of older adults and yielding heterogeneous manifestations concerning symptoms, severity and course has not been fully elucidated yet. This European, cross-sectional, non-interventional, naturalistic multicenter study systematically investigated socio-demographic and clinical correlates of early-onset depression (EOD) and LOD (age of onset ≥ 50 years) in 1410 adult in- and outpatients of both sexes receiving adequate psychopharmacotherapy. In a total of 1329 patients (94.3%) with known age of disease onset, LOD was identified in 23.2% and was associated with unemployment, an ongoing relationship, single major depressive episodes, lower current suicidal risk and higher occurrence of comorbid hypertension. In contrast, EOD was related to higher rates of comorbid migraine and additional psychotherapy. Although the applied study design does not allow to draw any causal conclusions, the present results reflect broad clinical settings and emphasize easily obtainable features which might be characteristic for EOD and LOD. A thoughtful consideration of age of onset might, hence, contribute to optimized diagnostic and therapeutic processes in terms of the globally intended precision medicine, ideally enabling early and adequate treatment allocations and implementation of respective prevention programs. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What are the cognitive profiles of older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI)? How do these profiles differ in terms of clinical, demographic, and brain structure features? • What is the main finding of this study? Using latent profile analysis, we identified three cognitive profiles, with differences in cognition, physical health, education, and brain structure. • What is the meaning of the finding? Older patients with rMDD can be grouped cross-sectionally based on distinct data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. Secondary cross-sectional analysis using latent profile analysis. Multisite clinical trial in Toronto, Canada. One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. We identified three latent profiles: Profile 1 (poor cognition ; n = 75, 42.1%), Profile 2 (intermediate cognition ; n = 75, 42.1%), and Profile 3 (normal cognition ; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD) has a poor response to the first-line standard antidepressant medications. This study aims to determine the effect of Vitamin B12 supplementation as an augmentation to the antidepressant medications as the first-line therapy in LLD to accelerate and/or maximize the response and remission. Materials and Methods: It was a prospective randomized controlled trial of 4 weeks; 62 depressed older adults (age >50 years) with low but not below the normal range of serum Vitamin B12 levels (>187 but <350 pg/ml) were randomized to receive either Vitamin B12 (7500 μg intramuscular injection over 15 days in 5 divided dosages) and an antidepressant (case) or only an antidepressant (control). Structured assessment of depressive disorder was carried out on days 0, 14, and 28, using hamilton rating scale for depression (HAM-D) and Geriatric Depression Scale Hindi version (GDS-H). Hindi Mental Status Examination was used at baseline to exclude primary cognitive impairment. Results: There was a significant decline in the depression scores in the Vitamin B12 supplementation group on both the HAM-D (P = 0.01, partial η2 = 0.113) and GDS (P = 0.01, partial η2 = 0.102) between days 0 and 28, with statistically more remitted subjects in the supplementation group (78% vs. 47%, P = 0.001). Conclusion: Vitamin B12 supplementation to standard antidepressant significantly improved the response and remission rates in subjects with low-normal serum Vitamin B12 levels. [ABSTRACT FROM AUTHOR]

Study rational and purpose: Web-based education has been proven effective in enhancing knowledge and confidence of health professionals in addressing mental health conditions. However, no web-based training, specific to geriatric depression, exists to date in Canada for educating future health and allied health professionals. The goal of this study was to develop, implement and evaluate a web-based learning module, Depression Assessment Training in Elderly (DATE), to enhance knowledge and confidence in screening for geriatric depression among social work, psychiatric nursing, and nursing students in an undergraduate Canadian university. Design/methodology/approach: This cross-sectional study utilized a set of quantitative surveys of undergraduate students in three different health and mental health disciplines in Canada. Findings: Findings suggest that the DATE module significantly improves confidence of all students in recognizing geriatric depression. Also, it increases clinical knowledge of geriatric depression in social work and psychiatric nursing students. Practical implications: The DATE module is now available for Canadian and international community of clinicians. Further research is needed to test the DATE in a larger sample of Canadian students of social work, psychiatric nursing, and nursing as well as among practicing clinicians. What is original/value of paper: The DATE is the first web-based learning module in Canada that contains clinical simulation case studies on the screening of geriatric depression. [ABSTRACT FROM AUTHOR]

Objective To explore the influencing factors of cognitive impairment in elderly patients with depressive disorder. Methods 119 elderly patients with depression were recruited in the 1st Affiliated Hospital of Kunming Medical University. MoCA was used to evaluate the cognitive function of the patients, and a regression model was established to analyze the influencing factors of cognitive impairment in elderly patients with depression. Results Age had a significant effect on the total score of cognition, visuospatial ability, executive function and language function ( P < 0.05) . The degree of anxiety had a significant effect on the total score of cognition, visuospatial ability, executive function, attention and working memory (P < 0.05）. Dyslipidemia had a statistically significant effect on the total score of cognition, visuospatial ability and executive function (P < 0.05）. The past medical history had a significant effect on the total score of cognition and language function (P < 0.05）. The sex, onset time, degree of depression, ApoE gene, occupation status and psychotic symptoms had statistically significant effects on individual cognitive function ( P < 0.05) . Conclusion Patients with late-life depressive disorder have obvious cognitive impairment. Age, anxiety, dyslipidemia, and past medical history may be the risk factors for cognitive impairment in elderly patients with depressive disorder. [ABSTRACT FROM AUTHOR]

Summary: Background: Detection and management of late-life depression largely relies on primary care. Yet in Singapore, older adults are unlikely to seek help for their mental health from their primary care providers. This qualitative descriptive study explores how late-life depression manifests to general practitioners (GPs) in the Singaporean primary care setting. Methods: Twenty-eight private GPs practicing in Singapore were asked about their clinical experience with late-life depression during semi-structured group and individual discussions conducted online. Participants were purposively sampled across age, gender, and ethnicity (Chinese, Malay, Indian). Transcripts were analysed with reflexive thematic analysis. Findings: To GPs, depression in older patients often manifests through somatic symptoms or subtle behavioural changes, only detectable through follow-ups or collateral history. GPs reported that older patients attribute depressive symptoms to normal ageing or do not mention them, particularly within an Asian culture encouraging stoic endurance. GPs perceived late-life depression as reactions to ageing-related stressors, with male, low-income, or institutionalised patients being at particular risk of insidious, severe depression. GPs noted ethnic differences regarding families’ involvement in care, which they described as helpful, but sometimes stress-provoking for patients. Fear of burdensomeness or loss of autonomy/social role could prompt rejection of diagnosis and treatment in patients. GPs considered good patient-doctor rapport as a facilitator at every step of the care process, noting more favourable prognosis in care-concordant patients. Interpretation: Depression in older adults in Singapore can be covert, with favourable outcomes relying on GPs’ ability to pick up on subtle changes, assess patients holistically, and build rapport with patients and families. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project “Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients’ Voice in Primary Care” [NUHSRO/2022/049/NUSMed/DFM].

BackgroundUnderlying inflammation is associated with an increased risk of depression in older adults. In this study, we examined the role of inflammatory biomarkers in antidepressant response in depressed older adults undergoing adjunct Tai Chi Chih (TCC) or Health education interventions.MethodsOlder adults aged 60 years and above with a diagnosis of major depression were randomized to 12 weeks of TCC versus Health and Wellness Education (HEW) as an adjunct therapy to their stable antidepressant treatment regimen. A panel of 19 cytokine/chemokines was measured at baseline and 12 weeks. Five factors were derived using factor analysis. General linear models were estimated to examine the change in factor scores and the association of these changes on depression remission rates, controlling for age, sex, and body mass index.ResultsOf the 170 randomized participants (TCC: n = 85 and HEW: n = 85), 55 TCC and 58 HEW completed the 3-month assessment. The groups did not differ at baseline in any measure. At follow-up, neither the changes in cytokine/chemokines scores nor the depression remission rate differed significantly between TCC and HEW. However, remitters and non-remitters differed significantly in changes in a factor composed of growth-regulated oncogene protein-alpha (GRO-alpha), epidermal growth factor (EGF), and soluble CD40 ligand (sCD40L). GRO-alpha and EGF levels (in both groups) were significantly increased in remitters compared to non-remitters.ConclusionChanges in certain cytokines/chemokines may accompany improvement in depressive symptoms in older adults. Future studies will need to explore the role of these molecules in remission of late-life depression.

With the acceleration of the aging process and change in social lifestyle， the prevalence rate of late-life depression （LLD） in the elderly is increasing year by year. As the most common mental disorder in the elderly， LLD seriously affects the quality of life of patients， and thus brings a heavy burden to the family and society. It may even become life-threatening for the elderly patients. The pathogenesis of LLD is still unclear， which may be caused by a combination effects of biological， social and psychological factor. Given the declined body functions and more comorbid physical diseases in the elderly population， the diagnosis and treatment of LLD patients would be different from that of younger adult patients with depression. This paper reviews the epidemiological characteristics， clinical evaluation， diagnosis， comorbidity， treatment and intervention of LLD， and focuses on the selection of therapeutic drugs and adverse reactions， in order to provide references for better diagnosis and treatment of LLD and improve the prognosis of patients.