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.

OBJECTIVE: 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).
METHODS: Monocentric, cross-sectional study.
METHODS: University Psychiatric hospital, memory clinic and outpatient neurology practice.
METHODS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

BACKGROUND: Late-life depression (LLD) is associated with cognitive impairment, yet substantial heterogeneity exists among patients. Data on the extent of cognitive impairments is inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant vs. nonresistant LLD and aimed to identify distinct cognitive subgroups. Additionally, we examined whether cognitive subgroups differentially responded to treatment with bilateral repetitive transcranial magnetic stimulation (rTMS).
METHODS: 165 patients with LLD were divided into treatment-resistant and nonresistant groups and compared to healthy controls (HC) on measures of executive function, information processing speed, verbal learning, and memory. Cluster analysis identified subgroups based on cognitive scores. Demographic and clinical variables, as well as outcomes with bilateral rTMS, were compared between cognitive subgroups.
RESULTS: Patients with LLD, particularly TRD, exhibited significantly worse cognitive performance than HC. A three-cluster solution was found, including \"Cognitively Intact\" (n = 89), \"Cognitively Diminished\" (n = 29), and \"Impaired Memory\" (n = 47) subgroups. Both the \"Cognitively Diminished\" and \"Impaired Memory\" subgroups had more anxiety symptoms and a higher proportion of patients with TRD than the \"Cognitively Intact\" group, though the latter did not survive multiple comparison correction. No significant differences were observed in outcomes to rTMS treatment.
CONCLUSIONS: Patients with LLD exhibited impairments across cognitive domains, which were more pronounced in TRD. Three identified cognitive subgroups responded similarly to rTMS treatment, indicating its effectiveness across cognitive profiles, especially when medications are not tolerated. Future research should examine the relationship among cognitive subgroups, cognitive decline, and neurodegeneration.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: 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).
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: 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.

BACKGROUND: The longitudinal course of late-life depression remains under-studied.
OBJECTIVE: To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns.
METHODS: 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.

UNASSIGNED: This study aims to assess the efficacy of mindfulness-based cognitive therapy (MBCT) in alleviating depression in older adults.
UNASSIGNED: A comprehensive search was conducted in 4 electronic databases and 1 registered database from inception up to July 2021 to identify relevant trials. The meta-analysis employed Hedge\'s g, along with its 95% CI, and associated z and P-values for the included studies, utilizing Comprehensive Meta-Analysis software.
UNASSIGNED: Qualitative synthesis was performed on 5 eligible studies. Evaluation of methodological quality and bias risk across the papers involved scrutiny of key variables due to the heterogeneous research formats. Our findings indicated a significant moderating effect of MBCT against current depressive symptoms in older adults (g = 0.53, 95% Confidence Intervals (CI) = 0.31-0.75) and a similar effect size for anxiety (g = 0.43, 95% CI = 0.20-0.65). However, caution is warranted due to the limited number of studies and potential publication bias. Further extensive research with longer follow-up measures and larger sample sizes is essential.
UNASSIGNED: This study underscores the effectiveness of MBCT as a treatment for anxiety and despair in older individuals. Mindfulness-based cognitive therapy should be recommended for its positive impact on older adults with depression, and the involvement of authorized psychiatric nurses is crucial for conducting successful MBCT interventions. However, caution is warranted due to the limited number of studies and potential publication bias. Further extensive research with longer follow-up measures and larger sample sizes is essential.

BACKGROUND: Late-life depression (LLD) is highly prevalent, especially in people aged 80 years and older. We aimed to investigate predictors and their influence on depressive symptoms in LLD.
METHODS: We analysed data from the NRW80+ study, a population-based cross-sectional study of individuals aged 80 years and older. Data from n = 926 cognitively unimpaired participants were included. We reduced 95 variables to 21 predictors of depressive symptoms by using a two-step cluster analysis (TSCA), which were assigned to one of four factors (function, values and lifestyle, autonomy and contentment, biological-somatic) according to a principal component analysis. A second TSCA with complete data sets (n = 879) was used to define clusters of participants. Using weighted mean composite scores (CS) for each factor group, binary logistic regression analyses were performed to predict depressive symptoms for each cluster and the total population.
RESULTS: The second TSCA yielded two clusters (cluster 1 (n = 688), cluster 2 (n = 191)). The proportion of participants with depressive symptoms was significantly higher in cluster 2 compared to cluster 1 (39 % vs. 15 %; OR = 3.6; 95 % CI 2.5-5.1; p < .001). Participants in cluster 2 were significantly older (mean age 88 vs. 85 years; p < .001), with a higher proportion of women (56 % vs. 46 %; OR = 1.5; 95 % CI 1.1-2.0; p = .016), had a higher BMI (p = .017), lower financial resources (OR = 2.3; 95 % CI 1.6-3.5; p < .001), lower educational level (OR = 1.8; 95 % CI 1.2-2.5; p = .002), higher proportion of single, separated or widowed participants (OR = 1.9; 95 % CI 1.3-2.6; p < .001) and a smaller mean social network (p = .044) compared to cluster 1. Binary logistic regression analyses showed that the weighted mean CS including the autonomy and contentment predictors explained the largest proportion of variance (22.8 %) for depressive symptoms in the total population (Nagelkerke\'s R2 = 0.228, p < .001) and in both clusters (cluster 1: Nagelkerke\'s R2 = 0.171, p < .001; cluster 2: Nagelkerke\'s R2 = 0.213, p < .001), respectively.
CONCLUSIONS: The main limitations are the restriction to cognitively unimpaired individuals and the use of a self-rated questionnaire to assess depressive symptoms.
CONCLUSIONS: Psychological factors such as autonomy and contentment are critical for the occurrence of depressive symptoms at higher age, independent of the functional and somatic status and may serve as specific targets for psychotherapy.

UNASSIGNED: Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear.
UNASSIGNED: This study profiled the current state of global research on LLD and predicted future research trends in the field.
UNASSIGNED: Literature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages.
UNASSIGNED: In total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The International Journal of Geriatric Psychiatry was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots.
UNASSIGNED: Late-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.