Late-life Depression Patients Research Articles

The modulation effect of cognition on mentalization in late-life depression: a study of gaze perception-a potential screening tool for high-risk group of late-life depression.

Impairment in mentalization is implicated in the development and maintenance of depression. Major depressive disorders showed significant impairment in social cognition and such impairment appears to be positively associated with the severity of depression. Self-referential gaze perception (SRGP), a measurement of mentalization, was predominantly measured in patients with psychosis but rarely examined in late-life depression (LLD). To assess the effect of cognition on the interpretation bias of mentalization, 29 LLD patients and 29 healthy controls were asked to judge if various gaze directions were directed to self in SRGP. Patients with better cognition showed less unambiguous-SRGP bias than those with worse cognitive scores; this difference was not found in healthy controls. Global cognition and executive function contributed to the SRGP rate in patients. The current study is the first study to explore the relationship between cognition and SRGP in the LLD population. Our study findings suggested that the cognitive function of LLD patients may contribute to the modulation of interpretation bias, which in turn underlie the role of SRGP bias. Greater SRGP bias in patients may reflect social cognition deterioration, impairing the social interaction and functioning of LLD patients. This highlights the need for early intervention and cognitive decline identification to facilitate better prognosis and treatment effectiveness; thus, further studies could navigate the potential of SRGP task as a screening tool for high-risk group of LLD likely to develop dementia.

Executive function deficits in patients with the first episode of late-life depression before and after SSRI treatment: A pilot fMRI study.

Executive function deficits (EFD) in late-life depression (LLD) has been reported to be associated with antidepressant treatment resistance, increased disability, and poor quality of life. However, the underlying neutral mechanisms of EFD in patients with the first episode of LLD remains unclear. A total of 27 patients with first-episode, drug-naive LLD and 27 non-depressed controls (NC) were recruited for the present research. Participants underwent the Trail Making Test, the 17-item Hamilton depression rating scale (HAMD-17) test, and task-state functional magnetic resonance imaging scans under the neutral Stroop task. LLD patients' executive functions, depressive symptoms, and brain activity were examined again after 6months of antidepressant treatment. Of the 27 LLD patients, 16 cases completed 6-month follow-ups. Patients in the LLD baseline group spent more time on the Trail Making Test A test than those in the NC group (p<0.05). In the presence of an incongruency between the word color and meaning, the accuracy rate of the neutral Stroop task in the LLD baseline group was lower, and the reaction time was greater than that in the NC group, with statistically significant difference (p<0.05). The HAMD-17 score in the LLD follow-up group was significantly lower than that in the LLD baseline group (p<0.05). More activated brain regions were present in the LLD baseline group than in the NC group when performing the neutral Stroop task. Compared with the LLD baseline group, abnormal activation of relevant brains in the cingulate-prefrontal-parietal network of LLD patients still existed in the LLD follow-up group. LLD patients engaged more brain areas than the NC group while performing the neutral Stroop task. Abnormal activation of the cingulate-prefrontal-parietal network could be a contributing factor to EFD in LLD. ChiCTR, ChiCTR2100042370 (Date of registration: 21/01/2021). We didn't enroll enough first-episode, LLD patients, the robustness of the findings need to be confirmed by large sample clinical trials.

A novel biomarker selection method using multimodal neuroimaging data.

Identifying biomarkers is essential to obtain the optimal therapeutic benefit while treating patients with late-life depression (LLD). We compare LLD patients with healthy controls (HC) using resting-state functional magnetic resonance and diffusion tensor imaging data to identify neuroimaging biomarkers that may be potentially associated with the underlying pathophysiology of LLD. We implement a Bayesian multimodal local false discovery rate approach for functional connectivity, borrowing strength from structural connectivity to identify disrupted functional connectivity of LLD compared to HC. In the Bayesian framework, we develop an algorithm to control the overall false discovery rate of our findings. We compare our findings with the literature and show that our approach can better detect some regions never discovered before for LLD patients. The Hub of our discovery related to various neurobehavioral disorders can be used to develop behavioral interventions to treat LLD patients who do not respond to antidepressants.

Static and dynamic functional connectivity of the habenula in late-life depression patient with suicidal ideation

BackgroundSuicide is one of the most lethal complications of late-life depression (LLD), and habenular dysfunction may be involved in depression-related suicidality and may serve as a potential target for alleviating suicidal ideation. This study aimed to investigate abnormal functional connectivity of the habenula in LLD patients with suicidal ideation. MethodsOne hundred twenty-seven patients with LLD (51 with suicidal ideation (LLD-S) and 76 without suicidal ideation (LLD-NS)) and 75 healthy controls (HCs) were recruited. The static functional connectivity (sFC) and dynamic functional connectivity (dFC) between the habenula and the whole brain were compared among the three groups, and correlation and moderation analyses were applied to investigate whether suicidal ideation moderated the relationships of habenular FC with depressive symptoms and cognitive impairment. ResultsThe dFC between the right habenula and the left orbitofrontal cortex (OFC) increased in the following order: LLD-S > LLD-NS > control. No significant difference in the habenular sFC was found among the LLD-S, LLD-NS and control groups. The dFC between the right habenula and the left OFC was positively associated with global cognitive function and visuospatial skills, and the association between this dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. ConclusionThe increased variability in dFC between the right habenula and left OFC was more pronounced in the LLD-S group than in the LLD-NS group, and the association between habenular-OFC dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD.

A mediation analysis of the role of total free fatty acids on pertinence of gut microbiota composition and cognitive function in late life depression

BackgroundExtensive evidence demonstrates correlations among gut microbiota, lipid metabolism and cognitive function. However, there is still a lack of researches in the field of late-life depression (LLD). This research targeted at investigating the relationship among gut microbiota, lipid metabolism indexes, such as total free fatty acids (FFAs), and cognitive functions in LLD.MethodsTwenty-nine LLD patients from the Cognitive Outcome Cohort Study of Depression in Elderly were included. Cognitive functions were estimated through the Chinese version of Montreal Cognitive Assessment (MoCA). Blood samples were collected to evaluate serum lipid metabolism parameters. Fecal samples were evaluated for gut microbiota determination via 16S rRNA sequencing. Spearman correlation, linear regression and mediation analysis were utilized to explore relationship among gut microbiota, lipid metabolism and cognitive function in LLD patients.ResultsSpearman correlation analysis revealed significant correlations among Akkermansia abundance, total Free Fatty Acids (FFAs) and MoCA scores (P < 0.05). Multiple regression indicated Akkermansia and total FFAs significantly predicted MoCA scores (P < 0.05). Mediation analysis demonstrated that the correlation between decreased Akkermansia relative abundance and cognitive decline in LLD patients was partially mediated by total FFAs (Bootstrap 95%CI: 0.023–0.557), accounting for 43.0% of the relative effect.ConclusionThese findings suggested a significant relationship between cognitive functions in LLD and Akkermansia, as well as total FFAs. Total FFAs partially mediated the relationship between Akkermansia and cognitive functions. These results contributed to understanding the gut microbial-host lipid metabolism axis in the cognitive function of LLD.

Gut Microbiota Dysbiosis and Inflammation Dysfunction in Late-Life Depression: An Observational Cross-Sectional Analysis.

There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD.

Grey matter abnormalities in major depressive disorder patients with suicide attempts: A systematic review of age-specific differences

BackgroundPrevious studies have reported alterations in brain structure in major depressive disorder (MDD) patients with suicide attempts. However, age-related changes in suicidal MDD patients remain unclear. MethodsWe performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, PubMed, and Web of Science were searched to identify relevant studies from inception to January 2023. All voxel-based and surface-based morphometry studies comparing suicidal MDD patients to MDD or healthy controls were included. Studies were then grouped by age range (old, middle-age, adolescent) and the commonalities and age-related structural brain alterations were summarized. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS). ResultsA total of 17 studies met the inclusion criteria, including 3 of late-life depression (LLD) patients, 11 of middle-aged depression (MAD) patients, and 3 of adolescent depression (AOD) patients. The majority of studies had moderate to high NOS scores, indicating good quality. Patients in all three age groups exhibited extensive alterations in the lateral, medial, and orbital regions of the frontal lobes. Furthermore, suicidal MAD patients showed a specific decrease in the gray matter volume of the dorsolateral prefrontal cortex compared to suicidal LLD patients. Cortical thickness and left angular gyrus volume were decreased in suicidal MAD and suicidal LLD patients, but increased in suicidal AOD patients. ConclusionThis systematic review summarizes structural brain changes in suicidal MDD patients at three age groups: elderly, middle-aged, and adolescent. These findings help elucidate the common circuitry of MDD related to suicide over the lifespan and highlight unique circuitry associated with different ages. These findings may help predict the risk of suicide in MDD patients at different ages.

Association between suicide attempts and anemia in late-life depression inpatients

BackgroundAnemia is strongly associated with late-life depression (LLD), however, few studies have investigated the relationship between anemia and suicide attempts in LLD patients. It is still challenging to predict suicide risk in patients with depression. Therefore, there is growing interest in potential biomarkers of depressive disorders and suicidal behavior, which may play a significant role in the early diagnosis and treatment of depression. This study aimed to compare serum ferritin, folate, vitamin B12, and erythrocyte parameter levels in patients with LLD with those in healthy older adults, and the relationship between serum ferritin, folate, vitamin B12, and suicide attempts in patients.MethodsSerum ferritin, folate, vitamin B12, and erythrocyte parameter levels were measured in 66 hospitalized LLD patients (30 without suicide attempt, 36 with suicide attempt) and 47 healthy individuals. All participants were surveyed for basic conditions and suicide attempts, and depression was assessed in LLD patients.ResultsSerum ferritin, folate, vitamin B12, red blood cell count, hemoglobin, hematocrit, mean platelet volume and plateletcrit levels were significantly lower in LLD patients compared with healthy older adults (P < 0.05). Further analysis of the relationship between serum ferritin, folate, and vitamin B12 levels and LLD patients’ suicide attempts and showed a significant negative association between serum folate and vitamin B12 and suicide attempts (P < 0.05).ConclusionsSerum ferritin, folate, vitamin B12, red blood cell count, hemoglobin, hematocrit, mean platelet volume and plateletcrit levels were significantly lower in LLD patients than in healthy older adults. In addition, reduced serum folate and vitamin B12 levels in patients may have some effect on suicide attempts. More mechanistic studies are needed to further explain this association.

23 Cognitive Reserve Moderates Cognitive Functioning in Late-Life Depression

Objective:The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR.Participants and Methods:Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (&lt;16) and high (&gt;=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults.Results:The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p &lt;.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis.Conclusions:Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD.

Disrupted functional connectivity of the habenula links psychomotor retardation and deficit of verbal fluency and working memory in late-life depression.

Functional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late-life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear. Overall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses. Compared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory). Patients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment.

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer's disease: a comparative study.

Alzheimer's disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD. A study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed. AD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores. AD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

Relationships Among Short Self-Reported Sleep Duration, Cognitive Impairment, and Insular Functional Connectivity in Late-Life Depression.

Both late-life depression (LLD) and short sleep duration increase the risk of cognitive impairment. Increased insular resting-state functional connectivity (FC) has been reported in individuals with short sleep duration and dementia. This study aimed to investigate whether short sleep duration is associated with impaired cognition and higher insular FC in patients with LLD. This case- control study recruited 186 patients with LLD and 83 normal controls (NC), and comprehensive psychometric assessments, sleep duration reports and resting-state functional MRI scans (81 LLD patients and 54 NC) were conducted. Patients with LLD and short sleep duration (LLD-SS patients) exhibited more severe depressive symptoms and worse cognitive function than those with normal sleep duration (LLD-NS patients) and NC. LLD-SS patients exhibited higher FC between the bilateral insula and inferior frontal gyrus (IFG) pars triangularis than LLD-NS patients and NC, while LLD-NS patients exhibited lower FC than NC. Increased insular FC was correlated with short sleep duration, severe depressive symptoms, and slower information processing speeds. Furthermore, an additive effect was found between sleep duration and LLD on global cognition and insular FC. LLD-SS patients exhibited impaired cognition and increased insular FC. Abnormal FC in LLD-SS patients may be a therapeutic target for neuromodulation to improve sleep and cognitive performance and thus decrease the risk of dementia.

Lower Dorsal Lateral Prefrontal Cortex Functional Connectivity in Late-Life Depression With Suicidal Ideation

The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

A voxel-based morphometry investigation of brain structure variations in late-life depression with insomnia.

Late-life depression (LLD) is linked to various medical conditions and influenced by aging-related processes. Sleep disturbances and insomnia symptoms may be early indicators or risk factors for depression. Neuroimaging studies have attempted to understand the neural mechanisms underlying LLD, focusing on different brain networks. This study aims to further delineate discriminative brain structural profiles for LLD with insomnia using MRI. We analyzed 24 cases in the LLD with insomnia group, 26 cases in the LLD group, and 26 in the healthy control (HC) group. Patients were evaluated using the Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Index (PSQI). Structural MRI data were gathered and analyzed using voxel-based morphometry (VBM) to identify differences in gray matter volume (GMV) among the groups. Correlation analyses were conducted to explore the relationships between GMV and clinical characteristics. Significant difference in sex distribution was observed across the groups (p = 0.029). However, no significant differences were detected in age and MMSE scores among the groups. LLD with insomnia group exhibited significantly higher HAMA (p = 0.041) and PSQI scores (p < 0.05) compared to the LLD group. ANOVA identified significant difference in GMV of anterior lobe of cerebellum (peak MNI coordinate: x = 52, y = -40, z = -30) among HC, LLD, and LLD with insomnia. Post-hoc two-sample t-tests revealed that the significant difference in GMV was only found between the LLD group and the HC group (p < 0.05). The mean GMV in the cerebellum was positively correlated with HAMA scale in LLD patients (r = 0.47, p < 0.05). There is significant difference in GMV in the LLD group, the association between late-life depression and insomnia may be linked to anxiety. This study provides insights into the discriminative brain structural profiles of LLD and LLD with insomnia, advancing the understanding of the underlying neural mechanisms and potential targets for intervention.

Treatment strategy for late‐life depression

AbstractWith the unprecedented aging of the world's population, the number of elderly patients with depression is expected to increase. However, management and treatment of late‐life depression (LLD) is more difficult than in early adults. Prior to treatment, diagnosis must take into account the differentiation from, and comorbidity with, organic brain diseases such as dementia and delirium, as well as depression caused by other physical diseases or medications. As clinical features of LLD, treatment response tends to be poor in older patients and recurrence rates are higher than those in early adult patients, therefore psycho‐social interventions on the basis of the patient's background and condition are important for LLD. The first‐line treatment strategy generally depends on the severity of the depression. Systematic psychotherapies, including cognitive behavioral therapy and problem‐solving therapy, have been reported to reduce depressive symptoms in LLD. Regarding pharmacotherapy, newer antidepressants are recommended for LLD, but careful attention to adverse events is required. Treatment using neuromodulation is also reported to be useful for LLD. In the current review, for further‐line treatment, treatment strategies were divided according to the level of first‐line treatment response. Evidence indicates that LLD is more heterogeneous than depression in younger adults, therefore when treating LLD patients it is necessary to take various conditions and situations into consideration, and to provide detailed treatment that is tailored to each patient.

Simultaneous measurement of amino acid enantiomers in the serum of late-life depression patients using convenient LC–MS/MS method with Nα-(5-fluoro-2,4-dinitrophenyl)-l-leucinamide Derivatization

D-amino acids may be indicators of late-life depression but separation and quantification of enantiomers which differ only by optical rotation sign remain challenging due to their identical physical and chemical properties. A convenient LC-MS/MS method was developed for the simultaneous measurement of l- and d-amino acids based on the chiral derivatization reagent, Nα-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide, and conventional octadecylsilane reversed-phase column. Methanol was used as the extraction solvent and a single-step derivatization reaction using volatile triethylamine eliminated the requirement for desalination prior to LC-MS/MS. Simultaneous separation and identification of 21 amino acids and the enantiomeric compositions of the 18 chiral proteogenic entities were achieved. Low limits of detection (0.03–4.0 nM), wide linear range (0.01–20 μM), good precision (RSDs < 10 %) and negligible matrix effects indicated the suitability of the method. Application of the method to the quantification of serum chiral amino acids in late-life depression patients (n = 40) and controls (n = 35) found a total of 17 L-amino acids, 14 D-amino acids, DL-asparagine, glycine and γ-aminobutyric acid. The statistical evaluation showed significant differences of glycine, L-threonine and D-methionine between late-life depression patients and controls, indicating that these are potential biomarkers of late-life depression.

Altered topological properties of functional brain networks in patients with first episode, late-life depression before and after antidepressant treatment.

To preliminarily explore the functional activity and information integration of the brains under resting state based on graph theory in patients with first-episode, late-life depression (LLD) before and after antidepressant treatment. A total of 50 patients with first-episode LLD and 40 non-depressed controls (NCs) were recruited for the present research. Participants underwent the RBANS test, the 17-item Hamilton depression rating scale (HAMD-17) test, and resting-state functional MRI scans (rs-fMRI). The RBANS test consists of 12 sub-tests that contribute to a total score and index scores across the five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Escitalopram or sertraline was adopted for treating depression, and the dosage of the drug was adjusted by the experienced psychiatrists. Of the 50 LLD patients, 27 cases who completed 6-month follow-ups and 27 NCs matched with age, sex, and education level were included for the final statistical analysis. There were significant differences in RBANS total score, immediate memory, visuospatial/constructional, language, attention, and delayed memory between LLD baseline group and NCs group (P < 0.05). Considering the global attribute indicators, the clustering coefficient of global indicators was lower in the LLD baseline group than in the NCs group, and the small-world attribute of functional brain networks existed in all three groups. The degree centrality and node efficiency of some brains were lower in the LLD baseline group than in the NCs group. After 6 months of antidepressant therapy, the scores of HAMD-17, immediate memory, language, and delayed memory in the LLD follow-up group were higher than those in the LLD baseline group. Compared with the LLD baseline group, the degree centrality and node efficiency of some brains in the cognitive control network were decreased in the LLD follow-up group. The ability to integrate and divide labor of functional brain networks declines in LLD patients and linked with the depression severity. After the relief of depressive symptoms, the small-world attribute of functional brain networks in LLD patients persists. However, the information transmission efficiency and centrality of some brain regions continue to decline over time, perhaps related to their progressive cognitive impairment.

Task-based functional connectivity reveals aberrance with the salience network during emotional interference in late-life depression

Objectives Late-life depression (LLD) is a common and debilitating disorder. Previously, resting-state studies have revealed abnormal functional connectivity (FC) of brain networks in LLD. Since LLD is associated with emotional-cognitive control deficits, the aim of this study was to compare FC of large-scale brain networks in older adults with and without a history of LLD during a cognitive control task with emotional stimuli. Methods Cross-sectional case-control study. Twenty participants diagnosed with LLD and 37 never-depressed adults 60–88 years of age underwent functional magnetic resonance imaging during an emotional Stroop task. Network-region-to-region FC was assessed with seed regions in the default mode, the frontoparietal, the dorsal attention, and the salience networks. Results FC between salience and sensorimotor network regions and between salience and dorsal attention network regions were reduced in LLD patients compared to controls during the processing of incongruent emotional stimuli. The normally positive FC between these networks were negative in LLD patients and inversely correlated with vascular risk and white matter hyperintensities. Conclusions Emotional-cognitive control in LLD is associated with aberrant functional coupling between salience and other networks. This expands on the network-based LLD model and proposes the salience network as a target for future interventions.

The impact of depression on language function in individuals with Alzheimer’s disease: a pre/post-treatment design

BackgroundIt is uncertain whether depression might affect cognitive function in Alzheimer’s disease (AD). Most of studies on the effect of depression treatment on cognitive function in AD were briefly evaluated by Mini-Mental State Examination (MMSE). MMSE is poor sensitive to detect cognitive change. This study examined the cognitive response to depression treatment in AD via multi-domain assessment. In addition, we explored whether effect of depression treatment in AD is different those of late-life depression (LLD).MethodsThis study include AD patients with depression (AD + D) and without depression (AD − D), LLD patients (LLD), and healthy controls (HC). The patients were treated according to their diagnosis for 16 weeks: acetylcholinesterase inhibitors (AChEIs) and selective serotonin reuptake inhibitors (SSRIs) for AD + D, AChEIs for AD − D, and SSRIs for LLD. The cognitive changes from pre- to post-treatment were compared between AD + D and AD − D or LLD and HC. An independent sample t test was performed to compare the degree of change between the groups. Paired t tests were used to determine cognitive function changes in each depression treatment responder group.ResultsAt baseline, AD + D had more impairment in language function compared to AD − D, and LLD had greater deficit in executive function than HC. After depression treatment, more impaired cognitive domains at baseline were improved in AD + D and LLD, respectively. Moreover, AD + D showed an improvement in the global cognitive function (MMSE).ConclusionsResults indicated that language function was influenced by depression in AD, which is first evidence for specific cognitive domain related to depression in AD. Our finding indicates that depression could negatively impact cognitive function, and depression treatment may have beneficial cognitive effect in both AD and LLD. This study suggests the importance of early detection and treatment of depression in AD and LLD.Trial registration Clinical Research Information Service, CRIS, ID#: KCT0004041, Registered 5 June 2019, retrospectively registered after first patient enrollment date (4 March 2014) https://cris.nih.go.kr/cris/search/detailSearch.do?seq=14140&status=5&seq_group=14140&search_page=M.

Multimodal brain connectome-based prediction of suicide risk in people with late-life depression

Suicidal ideation, plans and behavior are particularly serious health issues among the older population, resulting in a higher likelihood of deaths than in any other age group. The increasing prevalence of depression in late life reflects the urgent need for efficient screening of suicide risk in people with late-life depression. Employing a cross-sectional design, we performed connectome-based predictive modelling using whole-brain resting-state functional connectivity and white matter structural connectivity data to predict suicide risk in late-life depression patients (N = 37 non-suicidal patients, N = 24 patients with suicidal ideation/plan, N = 30 patients who attempted suicide). Suicide risk was measured using three standardized questionnaires. Brain connectivity profiles were used to classify three groups in our dataset and two independent datasets using machine learning. We found that brain patterns could predict suicide risk in the late-life depression population, with the explained variance up to 30.34%. The functional and structural connectivity profiles improved the classification-prediction accuracy compared with using questionnaire scores alone and could be applied to identify depressed patients who had higher suicide risk in two independent datasets. Our findings suggest that multimodal brain connectivity could capture individual differences in suicide risk among late-life depression patients. Our predictive models might be further tested to help clinicians identify patients who need detailed assessments and interventions. The trial registration number for this study is ChiCTR2200066356.