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It is broadly acknowledged that the onset of dementia in Alzheimer’s disease (AD) may be modifiable by the management of risk factors. While several recent guidelines and multidomain intervention trials on prevention of cognitive decline address lifestyle factors and risk diseases, such as hypertension and diabetes, a special reference to the established risk factor of depression or depressive symptoms is systematically lacking. In this article we review epidemiological studies and biological mechanisms linking depression with AD and cognitive decline. We also emphasize the effects of antidepressive treatment on AD pathology including the molecular effects of antidepressants on neurogenesis, amyloid burden, tau pathology, and inflammation. We advocate moving depression and depressive symptoms into the focus of prevention of cognitive decline and dementia. We constitute that early treatment of depressive symptoms may impact on the disease course of AD and affect the risk of developing dementia and we propose the need for clinical trials.

Background Late-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective. Psychotherapy may be particularly beneficial for LLD due to specific psychological conditions in old age and a low risk of side effects. Although cognitive behavioural therapy (CBT) is highly established and effective in depression in young and mid-life there is only a limited number of small studies on CBT in LLD. An LLD-specific CBT has not yet been compared to an active, but unspecific supportive psychological intervention in a multicentre trial. Methods Here we present the design of the CBTlate trial, which is a multicentre, randomized, observer-blinded, active-controlled, parallel group trial. CBTlate aims at including 248 patients with LLD of both genders at 7 sites in Germany. The purpose of the study is to test the hypothesis that a 15-session individually-delivered CBT specific for LLD is of superior efficacy in reducing symptoms of depression in comparison with a supportive unspecific intervention (SUI) of the same quantity. The intervention includes 8 weeks of individual treatment sessions twice per week and a follow-up period of 6 months after randomization. The primary end point is the severity of depression at the end of treatment measured by the self-rated 30-item Geriatric Depression Scale (GDS). Secondary endpoints include depressive symptoms at week 5 and at follow-up (6 months after randomization). Additional secondary endpoints include the change of depressive symptoms assessed with a clinician-rating-scale and a patient reported outcome instrument for major depressive disorder, anxiety symptoms, sleep, cognition, quality of life, and overall health status from baseline to end-of treatment and to end of follow-up. Add-on protocols include MRI and the collection of blood samples. Discussion This study is the first multicentre trial of a specific CBT intervention for LLD compared to an unspecific supportive psychological intervention administered in a specialist setting. It has important implications for developing and implementing efficient psychotherapeutic strategies for LLD and may be a significant step to broaden treatment options for people suffering from LLD. Trial registration ClinicalTrials.gov (NCT03735576, registered on 24 October 2018); DRKS (DRKS00013769, registered on 28 June 2018).

Late-life depression (LLD) is a common disorder, especially in the age group of 80 years and older. The aim of this analysis is the longitudinal evaluation of predictors of LLD in a population-representative sample. In the NRW80+ study, participants (age≥80 years) representative for the German state of North Rhine-Westphalia were comprehensively characterised at two time points (baseline: 2017 (n = 1863); follow-up/FU: 2019/2020 (n = 912)). Recruitment was based on 55 randomly selected community registries. The interviews were conducted by computer-assistance. We analysed data from 680 participants who were either cognitively unimpaired (CU) according to the DemTect test, had mild cognitive impairment (MCI) or dementia and had depression scores available at baseline as well as FU. Depression symptoms were assessed by the 'Depression in Aging Scale' (DIA-S). In previous analyses, 21 variables collected at baseline were identified in a data-driven procedure and divided into four different areas (function, values/lifestyle, autonomy/satisfaction and biological/somatic variables). To predict depressive symptoms at FU (DIA-S score ≥2/4), binary regression analyses were carried out for each diagnostic group with the four areas at baseline as predictors. Among the 680 participants, 79.0% were CU, 13.2% had MCI and 7.4% had dementia. There were significant group differences for the presence of depressive symptoms at FU between the different diagnostic groups (CU: 19.6%, MCI: 31.2%, dementia: 30.0%; p = 0.016). The binary regression analyses for the CU group indicated that the psychological variables (autonomy/satisfaction) explained the highest variance for depressive symptoms at FU (Nagelkerke's R  = 0.149). Contrary, in the MCI group, the biological-somatic variables explained 29.7% (Nagelkerke's R  = 0.297) and values/lifestyle variables 32.1% of the variance at FU (Nagelkerke's R  = 0.321), which was significantly higher than the variance explained by the autonomy/satisfaction model (Nagelkerke's R  = 0.224). The dementia diagnosis group did not show any significant regression models. For the longitudinal prediction of depressive symptoms, psychological variables contribute most significantly in the CU group, whereas in the MCI group, biological-somatic and values/lifestyle variables are more relevant. This could lead to new perspectives in prevention of LLD.

Background Late‐life depression (LLD) is a common disorder, especially in the age group of 80 years and older. The aim of this analysis is the longitudinal evaluation of predictors of LLD in a population‐representative sample. Methods In the NRW80+ study, participants (age≥80 years) representative for the German state of North Rhine‐Westphalia were comprehensively characterised at two time points (baseline: 2017 (n = 1863); follow‐up/FU: 2019/2020 (n = 912)). Recruitment was based on 55 randomly selected community registries. The interviews were conducted by computer‐assistance. We analysed data from 680 participants who were either cognitively unimpaired (CU) according to the DemTect test, had mild cognitive impairment (MCI) or dementia and had depression scores available at baseline as well as FU. Depression symptoms were assessed by the ‘Depression in Aging Scale’ (DIA‐S). In previous analyses, 21 variables collected at baseline were identified in a data‐driven procedure and divided into four different areas (function, values/lifestyle, autonomy/satisfaction and biological/somatic variables). To predict depressive symptoms at FU (DIA‐S score ≥2/4), binary regression analyses were carried out for each diagnostic group with the four areas at baseline as predictors. Results Among the 680 participants, 79.0% were CU, 13.2% had MCI and 7.4% had dementia. There were significant group differences for the presence of depressive symptoms at FU between the different diagnostic groups (CU: 19.6%, MCI: 31.2%, dementia: 30.0%; p = 0.016). The binary regression analyses for the CU group indicated that the psychological variables (autonomy/satisfaction) explained the highest variance for depressive symptoms at FU (Nagelkerke's R2 = 0.149). Contrary, in the MCI group, the biological‐somatic variables explained 29.7% (Nagelkerke's R2  = 0.297) and values/lifestyle variables 32.1% of the variance at FU (Nagelkerke's R2  = 0.321), which was significantly higher than the variance explained by the autonomy/satisfaction model (Nagelkerke's R2  = 0.224). The dementia diagnosis group did not show any significant regression models. Conclusion For the longitudinal prediction of depressive symptoms, psychological variables contribute most significantly in the CU group, whereas in the MCI group, biological‐somatic and values/lifestyle variables are more relevant. This could lead to new perspectives in prevention of LLD.

Background Late‐life depression (LLD) is a risk factor for Alzheimer's disease (AD) dementia. Previous morphological studies have often associated LLD with atrophy within the medial temporal lobe (MTL), including the hippocampus. A number of previous studies have demonstrated the changes in several MTL subfields in LLD, such as the perirhinal cortex (PrC), cornu ammonis (CA), dentate gyrus (DG), subiculum and entorhinal cortex (EC), but with inconsistent results, which may be explained by the relatively low image resolution of the 3T scanner used in the previous studies. Method A total of 93 individuals over the age of 60 were included in this study, of which 23 LLD patients and 29 normal controls without a history of depression underwent T1 and T2tse scans on a 7‐Tesla MRI scanner. Images were pre‐processed and roughly segmented into CA1‐3, DG, SUB, EC, and PrC (area 35, 36) using the Automated Segmentation Hippocampal Subfields (ASHS) and further separated into anterior and posterior (head and body). All segmented images were manually edited. Group comparisons of MTL subfield volumes were made, adjusting for age, sex, and years of education. Cognitive and clinical scores were correlated with the volume of each subfield. Result LLD and controls did not differ in total hippocampal volume. LLD showed reduced volume in the head portion of the right DG (p=0.05) and a trend towards reduced ratio between left and right EC (p=0.07). No other group differences were observed. Correlational analyses revealed a significant association between bilateral hippocampal volume and TMT‐A speed, as well as the anxiety subscale of the Geriatric Depression Scale (GDS). Subfield analyses revealed significant associations between the anxiety subscale of the GDS and bilateral DG head volume (left: r=‐0.36, p=0.006; right: r=‐0.42, p=0.002) and between the left CA1 body and the cognition subscale of the GDS (r=0.29, p=0.03). Conclusion Using ultra‐high field MRI, we demonstrated an anterior‐posterior differentiation along the hippocampal long axis in the involvement of cognitive and clinical symptoms in LLD. Future work should investigate the relationship between AD pathological changes and behavioral symptoms in LLD and whether MTL subfields may play a mediating role.

Major depressive disorder (MDD) is common and associated with high social and economic burden. Knowledge of characteristics of hospitalized adults with MDD can help identify clinical treatment and prevention targets. The multicenter \"Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression\" (OASIS-D) study assessed characteristics of patients aged 18-75 years hospitalized between October 2020 and December 2024, who were admitted to a psychiatric inpatient unit for MDD at eight German centers. Baseline illness-, treatment-, and suicidality-related characteristics of the overall sample are reported. Among 3795 patients (median age = 42.0, interquartile range [IQR] = 27.5-57.0 years; females = 53.9%) with MDD (severe episode = 75.3%, psychotic features = 7.9%; first episode = 34.9%; treatment-resistant depression [TRD] = 18.2%). Psychiatric comorbidities of MDD were present in 46.2% and included substance use disorder (18.9%), personality disorders (8.4%), stress/adjustment disorders (7.6%), and phobic/other anxiety disorders (6.6%). In 42.5%, the admission was prompted by a psychiatric emergency, primarily due to suicidality (35.0%), followed by stupor/refusal/intoxication/acute agitation (0.9%-1.5%), or danger to others/delirium (0.1%-0.3%). Overall, 72.0% of patients had active or passive suicidal thoughts, and 11.5% had attempted suicide within 2 weeks prior to admission. Furthermore, 83.9% had lifetime suicidal thoughts, and 36.0% had lifetime suicide attempts. Altogether, 76.8% had received outpatient psychiatric care within their lifetime (62.3% within 6 months), and 57.8% of patients had lifetime inpatient treatment for MDD. At admission, 71.6% of patients were prescribed psychiatric medications: antidepressants = 59.8%; antipsychotic = 25.1%, anxiolytics/hypnotics = 11.8%, and mood stabilizers = 8.6%. Additionally, 4.0% had previously received electroconvulsive therapy (ECT). The median hospitalization duration was 31.0 (IQR = 13.0, 57.0) days. Almost half of admissions in adults with MDD were considered emergencies, with 90% being related to suicidality, and only <60% received antidepressants at admission. These data underscore the need for early identification and treatment of adults with MDD, especially those with suicidality. Outcomes of this population required further study. ClinicalTrials.gov identifier: NCT04404309.