Distinct latent symptom profiles in late-onset depressive symptoms in community-dwelling older adults.

OBJECTIVES: To examine the symptom profiles of late-onset depressive symptoms in a sample of older adults. METHOD: The sample included 1,192 participants from the National Alzheimer's Coordinating Center Data Set. Participants were ≥65 years old, community-dwelling, and without cognitive impairment or a prior history of depression. Depressive symptoms were assessed using the Geriatric Depression Scale, 15-item (GDS-15). Latent class analysis (LCA) was used to identify and group participants based on profiles of depressive symptoms. RESULTS: LCA revealed three distinct symptom profiles: (1) an Anhedonia/Amotivation profile with a higher probability of endorsing a combination of low positive emotion and amotivation (6%), (2) an Amotivation/Withdrawal profile with a high probability of endorsing only amotivational depressive symptoms (35%), and (3) an asymptomatic profile with no probability of endorsing any depressive symptoms (59%). Amotivational depressive symptoms were observed across both symptomatic profiles, while depressed mood (e.g. sadness) did not predominantly characterize any profile in this sample. There were also significant differences among symptom profiles in terms of demographic and clinical characteristics. CONCLUSIONS: Findings highlight the importance of understanding depression at the symptom pattern level. A profile-based diagnostic approach may help improve the recognition of depressive symptoms in older adults.

Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics.

Cognitive deficiency is one of the fundamental characteristics of late-onset depression (LOD). Luteolin (LUT) possesses antidepressant, anti-aging, and neuroprotective properties, which can dramatically enhance cognition. The altered composition of cerebrospinal fluid (CSF), which is involved in neuronal plasticity and neurogenesis, directly reflects the physio-pathological status of the central nervous system. It is not well known whether the effect of LUT on LOD is in association with a changed CSF composition. Therefore, this study first established a rat model of LOD and then tested the therapeutic effects of LUT using several behavioral approaches. A gene set enrichment analysis (GSEA) was used to evaluate the CSF proteomics data for KEGG pathway enrichment and Gene Ontology annotation. We combined network pharmacology and differentially expressed proteins to screen for key GSEA-KEGG pathways as well as potential targets for LUT therapy for LOD. Molecular docking was adopted to verify the affinity and binding activity of LUT to these potential targets. The outcomes demonstrated that LUT improved the cognitive and depression-like behaviors in LOD rats. LUT may exert therapeutic effects on LOD through the axon guidance pathway. Five axon guidance molecules-EFNA5, EPHB4, EPHA4, SEMA7A, and NTNG-as well as UNC5B, L1CAM, and DCC, may be candidates for the LUT treatment of LOD.

Risk of Late-Onset Depression and Cognitive Decline: Results From Inflammatory Proteome Analyses in a Prospective Population-Based Cohort Study.

OBJECTIVE: Research suggests that inflammation is linked to both late-onset depression (LOD) and cognitive decline, and that LOD might have biological underpinnings differentiating it from recurrent depression. Evidence from inflammatory proteome analyses in large prospective cohorts is scarce. The aim of this study was to assess whether and which inflammation-related biomarkers are associated with LOD, recurrent depression, and cognitive decline due to vascular pathology (vascular dementia). DESIGN: Ongoing population-based cohort study of older adults followed for up to 17 years with regard to clinical diagnosis of various age-related diseases (ESTHER study, n = 9,940). SETTING: Longitudinal cohort started in 2000-2002 in a community setting in Saarland, a southwestern German state. PARTICIPANTS: Subgroup of randomly selected participants of the ESTHER study (n = 1,665). MEASUREMENTS: Inflammatory biomarkers were measured with the Olink Target 96 in baseline samples. RESULTS: Out of 78 biomarkers interleukin 10 (IL-10) and C-C chemokine ligand 4 (CCL4) were associated with significantly increased risk of LOD after multiple testing correction. Hazard ratios (95-confidence interval) per 1 standard deviation increase were 1.37 (1.15-1.63) for IL-10 and 1.34 (1.13-1.59) for CCL4. None of the inflammatory markers was associated with recurrent depression. The dose-response analysis showed a similar monotonic risk increase for LOD and vascular dementia with increasing IL-10 levels. CONCLUSION: These results suggest that inflammatory markers are involved in the etiology of LOD, but not of recurrent depression and that LOD and vascular dementia might share common inflammatory etiology with respect to IL-10.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

OBJECTIVE: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. METHODS: Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. RESULTS: All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (ß = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (ß coefficient = 5.89, P = .03). CONCLUSION: Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.

[Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression].

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression.

OBJECTIVE: Cerebral small vessel disease (SVD) is associated with late-onset depression and increases the risk for depression after stroke. We aimed to investigate baseline predictors of depression after long-term follow-up in patients with SVD, initially presenting with first-ever lacunar stroke, free of depression and cognitive impairment. METHODS: A total of 294 patients with SVD were evaluated 3-5 years after the qualifying event. We analyzed baseline demographic data, vascular risk factors, functional status expressed as a score on modified Rankin Scale (mRS), cognitive status, presence of depression, total number of lacunar infarcts and severity of white matter hyperintensities (WMH) on MRI with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. RESULTS: On follow-up, depression was registered in 117 (39.8%) SVD patients. At the baseline, patients with depression compared with non-depressed were older (64.4 vs 60.9 years; p = 0.007), had higher mRS score (2.8 ± 0.7 vs 1.5 ± 0.7; p < 0.0001) and had more severe lesions on MRI scales (p < 0.0001 for all parameters). On follow-up, depressed patients more frequently exhibited cognitive decline (75.2% depressed vs 56.5% non-depressed; p = 0.003). No difference was detected in risk factor frequency between groups. Multivariate Cox regression analysis adjusted by age and gender revealed independent predictors of depression: baseline mRS >2 (HR 2.17, 95%CI 1.74-2.72; p < 0.0001) and tARWMC (HR 1.05, 95%CI 1.02-1.09; p = 0.005), and cognitive decline on follow-up (HR 1.80, 95%CI 1.12-2.89; p = 0.015). CONCLUSIONS: Baseline functional status and severity of WMH and development of cognitive decline predict the occurence of late-onset depression in patients with SVD.

Comparison of Clock Test Deficits Between Elderly Patients With Early and Late Onset Depression.

To compare clock test deficits in elderly patients with early onset depression (EOD) and late onset depression (LOD), we assessed 32 elderly healthy controls (HCs), 26 patients with EOD, and 27 patients with LOD with the clock drawing test (CDT), clock setting test, clock reading test, and the Tübingen Clock Questionnaire testing semantic memory about clock times. There was no significant difference in depression severity between patients with EOD and LOD. Patients with LOD had significantly lower scores on the CDT than patients with EOD and HCs. Semantic memory impairment concerning minute hand functionality was highly correlated with CDT performance and was significantly different between the EOD and the LOD groups. It can be suggested that significant differences in cognitive impairment severity between patients with EOD and LOD can be detected with CDT. Semantic memory impairment concerning minute hand functionality might affect CDT test results in elderly patients with depression.

Genetic variant of AKT1 and AKTIP associated with late-onset depression in a Brazilian population.

OBJECTIVES: Examine the association between polymorphisms in the AKT1 and AKTIP genes and late-onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65 years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter-related disorders, such as depression. The identification of a novel AKT1-binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD. DESIGN: Genotype tagSNPs in the AKT1 and AKTIP in LOD patients and controls. SETTINGS: An academic medical center. PARTICIPANTS: Sample composed by 190 outpatients with LOD and 77 healthy individuals. MEASURES: The participants were evaluated using Diagnostic and Statistical Manual IV criteria, MINI-PLUS and the Geriatric Depression Scale. RESULTS: Our findings suggested an association between the tagSNP rs3730358 homozygous A/A (p = 0.006) and LOD. A strong association of allele A and increased association for LOD was demonstrated with tagSNP rs3730358 (p-value = 0.003). LIMITATIONS: Limitation include composition of our control group, where the exclusion criteria generated a kind of super-healthy older group what might have produced a hidden stratification when compared with the LOD. CONCLUSION: This study is the first one to establish the association of the AKT1/AKTIP genes and LOD, and further studies are necessary to clarify the functional role of these proteins.

Increased frequency of cluster of differentiation 14 (CD14+) monocytes expressing interleukin 1 beta (IL-1ß) in Alzheimer's disease patients and intermediate levels in late-onset depression patients.

OBJECTIVE: Depression might be a prodromal stage of dementia. Many factors contribute to the etiology of depression and dementia, being inflammation one of those. The present work measured and analyzed immune molecules involved in the innate immunity on cluster of differentiation 14 (CD14+) monocytes trying to investigate any relationship among late-onset depression (LOD) and Alzheimer's disease (AD). METHODS: Immune molecules were evaluated in monocytes of AD, LOD patients, and controls using flow cytometry. RESULTS: Interestingly, interleukin 1 beta (IL-1ß) expressing CD14+ monocytes were increased in AD patients compared with controls. LOD presented intermediate frequency of CD14+ monocytes expressing IL-1ß between controls and AD patients. CONCLUSION: Results suggest that an increased frequency of CD14+ monocytes expressing IL-1ß level could be a stage marker related to the pathophysiology of dementia process between normal aging and AD.

Late-onset depression in the absence of stroke: associated with silent brain infarctions, microbleeds and lesion locations.

BACKGROUND: Late-onset depression (LOD) is a frequent mood disorder among elderly. Previous studies have proved that LOD is associated with cerebral silent lesions especially white matter lesions (WML) and yielded the "vascular depression" hypothesis to explain the pathogenesis of LOD. However, there were relatively few studies about the association between silent brain infarctions (SBIs), microbleeds (MBs) and the prevalence of LOD. In this study we sought to evaluate the presence, accumulation and locations of SBIs and MBs, and explore the possible association between them and LOD. METHODS: 65 patients of LOD diagnosed according to DSM-IV and 270 subjects of control group were enrolled and scanned by MRI to analyze the presence, numbers and locations of SBIs and MBs. Clinical and radiological characteristics were compared between LOD patients and control group. Logistic regression models were constructed to identify the independent risk factors for LOD. RESULTS: LOD patients had higher prevalence and numbers of both SBIs and MBs. SBIs and MBs in the left hemisphere, SBIs in basal ganglia and lobar MBs were all independent risk factors for LOD. CONCLUSION: The presence of both SBIs and MBs were associated with a higher rate LOD. Lesions in some specific locations might be critical for the presence of LOD.

Predictors of length of hospital stay for patients with late-onset depression in Japan.

BACKGROUND: The length of hospital stay (LOHS) for elderly patients tends to be long. We aimed to identify factors related to long hospitalization periods for elderly Japanese patients with late-onset depression. METHODS: We retrospectively examined 133 patients with late-onset depression. Univariate and multivariate analyses were performed to confirm the relationship between each clinical feature and the duration of hospital stay. RESULTS: The mean LOHS was 83.9 ± 55.6 days. On the basis of univariate analysis, we found that living as a housewife, death of a close relative or friend, recurrent depression, melancholic features, and treatment with electroconvulsive therapy, tricyclic or tetracyclic antidepressants or mood stabilizer were associated with a longer LOHS. Multivariate analysis showed that treatment with tricyclic or tetracyclic antidepressants, atypical antipsychotics were associated with prolonged LOHS. CONCLUSIONS: These results suggest that job status, changes in household circumstances and the failure of initial treatment is responsible for the long LOHS in Japan.

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

BACKGROUND: Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies. AIMS: In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective. RESULTS: The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions. CONCLUSIONS: Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.

The clinical perspective on late-onset depression in European real-world treatment settings.

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.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Influence of gender and age on cognitive inhibition in late-onset depression: a case-control study.

OBJECTIVE: To compare cognitive inhibition performance between people with early-onset (EOD) or late-onset depression (LOD) and controls, and between women and men with LOD. METHODS: On the basis of a case-control design, global executive performance (Frontal Assessment Battery); verbal (Hayling), attention (Stroop), and motor (Go/No-Go) components of cognitive inhibition; mental shifting (Trail Making Test parts A and B); and updating in working memory (Wechsler Adult Intelligence Scale) were assessed in 40 participants (10 depressed women with LOD (i.e., ≥60 years old), 10 depressed women with EOD (i.e., <60 years old), 10 healthy women and 10 depressed men with LOD (i.e., ≥60 years old)). RESULTS: Older depressed women, irrespective of age of depression onset, had greater cognitive inhibition impairments (attention and verbal component) compared with healthy women. LOD was significantly associated with the attention component of cognitive inhibition impairment, unlike EOD (p = 0.026). No executive differences were found regarding age of first-onset depression in older depressed women, and between women and men with LOD. CONCLUSION: Cognitive inhibition impairment, and more specifically its attention component, was the main characteristic of depression in the studied sample of older adults, independently of gender and age of depression onset. It is essential to perform similar studies in both genders in view of future tailor-made therapeutic modalities.

Late-Onset Depression but not Early-Onset Depression may Increase the Risk of All-Cause Mortality in Older Age: 8-Year Follow-Up of the Salus in Apulia Study.

OBJECTIVES: Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. DESIGN: Longitudinal population-based study with 8-year follow-up. SETTING AND PARTICIPANTS: We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study. METHODS: LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. RESULTS: The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months). CONCLUSIONS AND IMPLICATION: In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.

The cognitive effects of adjunctive repetitive transcranial magnetic stimulation for late-onset depression: a randomized controlled trial with 4 week follow-up.

Objectives: Cognitive impairment is common and linked to poor outcomes in patients with late-onset depression (LOD). The cognitive effects of repetitive transcranial magnetic stimulation (rTMS) for LOD are not well understood. This study aimed to investigate the effects of rTMS on cognitive function in elderly patients with LOD. Methods: In total, 58 elderly patients (aged 60 to 75 years) with depression were enrolled and randomly assigned to an active rTMS group or a sham group. The participants received active or sham rTMS over the left dorsolateral prefrontal cortex for 4 weeks, 5 days a week, at a frequency of 10 Hz rTMS and 120% of the motor threshold (MT). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, the end of the 4 week treatment period, and at the 4 week follow-up. Results: The active rTMS group showed significant improvements in immediate memory and attention scores on the RBANS compared to the sham group. However, no significant differences were observed between the two groups in other cognitive domains assessed by the RBANS. No serious adverse events related to rTMS treatment were observed. Conclusion: Treatment with 120% MT rTMS was associated with improvement in cognitive defects related to the active phase of LOD. These findings suggest that rTMS could provide early improvements in cognitive function in clinical settings for elderly patients with LOD.Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=40698, identifier ChiCTR1900024445.

Effects of Health-Promoting Lifestyle on Late-Onset Depression in Older Adults: Mediating Effect of Meaning in Life and Interleukin-6 (IL-6).

Purpose: Late-onset depression (LOD) with poor treatment response has high incidence and mortality in the China's aged people, this study aims to explore the correlation between health-promoting lifestyle, meaning in life, interleukin-6 (IL-6) and LOD for providing scientific basis of LOD prevention and rehabilitation. Patients and Methods: A total of 496 LOD patients (study group) and healthy older adults (control group) were enrolled and investigated by using the Health-promoting lifestyle Profile-II, revised (HPLP-IIR), Meaning in Life Questionnaire-Chinese Version (MLQ-C), and Hamilton Depression Scale (HAMD). The interleukin-6 (IL-6) in the circulating blood was detected by utilizing ELISA kit. Results: The results showed that the scores of all factors in HPLP-IIR and MLQ were significantly lower and IL-6 level was higher in the study group than the control group. Scores of most factors in HPLP-IIR and MLQ negatively and IL-6 positively correlated with scores of subscales and total HAMD score. Meaning in life and IL-6 partially mediated the relationship between health-promoting lifestyles and depression severity in the study group, with the mediating effect explains 15.76% and 22.64% of the total effect, respectively. Conclusion: Health-promoting lifestyles, meaning in life, and IL-6 are predictors of LOD, and an unhealthy lifestyle could induce LOD through the mediating effect of meaning in life and IL-6 in older adults.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression.

Background: Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. Objective: The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. Methods: One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Results: Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Conclusion: Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.