Search

The Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) are commonly used scales to measure depression severity in older adults. We utilized data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) clinical trial to produce conversion tables relating PHQ-9 and MADRS total scores. We split the sample into training (N = 555) and validation samples (N = 187). Equipercentile linking was performed on the training sample to produce conversion tables for PHQ-9 and MADRS. We compared the original and estimated scores in the validation sample with Bland-Altman analysis. We compared the depression severity level using the original and estimated scores with Chi-square tests. The Bland-Altman analysis confirmed that differences between the original and estimated scores for at least 95 % of the sample fit within 1.96 standard deviations of the mean difference. Chi-square tests showed a significant difference in the proportion of participants at each depression severity category determined using the original and estimated scores. The conversion tables should be used with caution when comparing depression severity at the individual level. Our conversion tables relating PHQ-9 and MADRS scores can be used to compare treatment outcomes using aggregate data in studies that only used one of these scales. • Equipercentile linking was used to produce conversion tables for PHQ-9 and MADRS. • Total scores can be compared using the conversion table for aggregate data. • Comparing total scores between individuals should be done with caution. [ABSTRACT FROM AUTHOR]

Age at first onset of depression as a clinical factor affecting cognitive improvement in late life depression was investigated. This is a secondary analysis of an eight-week randomized controlled trial involving 452 elderly patients treated by vortioxetine, duloxetine or placebo (1:1:1). Patients were subcategorized into early-onset (LLD-EO) and late-onset (LLD-LO) groups divided by onset age of 50. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS). Vortioxetine and duloxetine exhibited advantages versus placebo in improving cognitive performance in the LLD-LO group, yet not in the LLD-EO group after eight weeks. Patients in the LLD-EO group showed overall advantage to placebo in depressive symptoms before endpoint (week 8) of treatment, while patients in the LLO-LO group showed no advantage until endpoint. Path analysis suggested a direct effect of vortioxetine (B = 0.656, p =.036) and duloxetine (B = 0.726, p =.028) on improving cognition in the LLD-LO group, yet in all-patients treated set both medications improved cognition indirectly through changes of depressive symptoms. Reliability of clinical history could raise caution as it was collected by subjective recall of patients. Age at first onset might affect cognitive improvement as well as change in depressive symptoms and its mediation towards cognitive improvement in late life depression treated with vortioxetine and duloxetine. • Vortioxetine and Duloxetine improved cognitive performance of elderly depressed patients with first onset after 50. • Patients with first depressive onset before 50 showed earlier symptomatic change than those with first onset after 50. • Vortioxetine and duloxetine showed direct treatment effect on improving cognition in patients with first episode after 50. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? We examined the impact of state and trait anxiety on cognitive performance in older adults with major depression. • What is the main finding of this study? In older adults with major depressive disorder, increases in individual levels of anxiety—both trait and state are associated with declines in cognitive performance including poorer memory and executive dysfunction while controlling for levels of depression. Higher levels of state anxiety between participants was associated with worse memory and global cognition. • What is the meaning of the finding? State and trait anxiety have a distinct negative impact on cognition in older adults with major depression which place them at greater risk for cognitive decline and thus, are important to consider when diagnosing and treating cognitive impairment in clinical practice. Anxiety superimposed on late life depression (LLD) results in greater changes to prefrontal and medial temporal brain regions compared to depression alone. Yet, the combined impact of anxiety and depression on cognition in LLD has not been thoroughly investigated. The current study investigated whether annual changes in state and trait anxiety were associated with cognitive changes in older adults with major depression. We hypothesized that the presence of anxiety among older depressed adults would be associated with worse cognitive performance in the domains of memory and executive functioning over time. Three-year longitudinal observational study of older adults with LLD who were offered antidepressant treatment. Academic Health Center. Participants included 124 adults aged 60+ who met criteria for major depression at baseline. The association between anxiety and cognition was examined with separate multilevel linear models that addressed both between-subject and within-person effects of state and trait anxiety on cognitive functioning tests. Individuals who experienced annual increases in anxiety above his/her personal average also experienced cognitive decline. Increases in state anxiety were associated with declines in memory and global cognition. By contrast, increases in trait anxiety were associated with declines in mental flexibility and memory. These findings remained significant even when controlling for changes in depression over time. In LLD, individual increases in state and trait anxiety were associated with cognitive declines in different domains. [ABSTRACT FROM AUTHOR]

Abstract Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors. • Positive affect, melancholic, typical, and atypical depression subtypes were identified. • Distinct associations with stressor profiles differentiated depression subtypes. • Atypical depression had the most significant associations with unique stressor profiles. • Childhood physical abuse was more likely for positive affect than atypical depression subtypes. [ABSTRACT FROM AUTHOR]

Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions. • Late life depression (LLD) differs from depression at earlier stages of life. • Older adults have unique risk factors linked to treatment resistant LLD (TRLLD). • Clinical phenotyping may help with individualized treatment planning for TRLLD. • Considerable research is still needed to better understand and treat TRLLD. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Are partnerships with community-based organizations (CBO) to augment standard collaborative care a feasible and effective approach to improve depressive symptoms in older adults? • What is the main finding of this study? Building partnerships with community-based organizations is a feasible and effective way for primary care clinics to improve care for depressed older adults. • What is the meaning of the finding? Primary care clinics and CBOs can partner successfully to improve the lives of older adults with depression. Collaborative care (CC) has demonstrated effectiveness for improving late-life depression in primary care, but clinics offering this service can find it challenging to address unmet social needs that may be contributing to their patients' depression. Clinics may benefit from better coordination and communication with community-based organizations (CBO) to strengthen depression treatment and to address unmet social needs. We evaluated the feasibility of adding a CBO to enhance standard collaborative care and the impact of such partnered care on older adults. Multisite, prepost evaluation. Eight (n = 8) partnerships between primary care clinics and community-based organizations in California. A total of 707 depressed older adults (60 years or older) as evidenced by having a score of 10 or more on the Patient Health Questionnaire (PHQ-9) received care under the Care Partners project. A CBO partner was added to augment CC for late-life depression in primary care. The PHQ-9 was used to identify depressed older adults and to monitor depression symptom severity during a course of care. At baseline, the average PHQ-9 depression score across the partnerships was 15, indicating moderate depression severity. Participating patients saw an average 7-point reduction in their PHQ-9 score, baseline to last score assessed, with nearly half of all participants (48.4%) experiencing a 50% or greater improvement from their baseline score. Our findings suggest that partnering with a community-based organization is a feasible and effective way for primary care clinics to address late-life depression in their patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD. METHODS: 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance. RESULTS: Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed. CONCLUSIONS: The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD.

Objectives: Late Life Depression (LLD) is associated with increased mortality rates, but it remains unclear which depressed patients are at increased risk. This study examined the mortality risk of previously identified subgroups of depressed older patients based on age‐related clinical features (the presence of physical and cognitive frailty). Methods: A six‐year follow‐up of a clinical cohort study including 375 depressed older patients and 132 non‐depressed persons (NESDO). Depressed patients were diagnosed with the Composite International Diagnostic Interview (CIDI) according to DSM‐IV criteria and classified by latent profile analysis on depressive symptom severity, cognitive domains and physical frailty. We estimated the hazard rate of mortality for the four depressed subgroups compared to non‐depressed persons by applying Cox‐regression analyses. Models were adjusted for age, sex and education as confounders and for explanatory variables per pathway in separate models: somatic burden, lifestyle characteristics, vascular burden or inflammation markers. Results: A total of 61/375 (16.3%) depressed patients and 8/132 (6.1%) non‐depressed persons died during the 6‐year follow‐up. Two of the four subgroups (n = 186/375 (50%) of the depressed sample) had a higher hazard rate (HR) for mortality compared to non‐depressed participants, that is, frail‐depressed patients (HR = 5.25, [95%‐CI: 2.13–13.0]) and pure mild depressed patients (HR = 3.32 [95%‐CI: 1.46–7.58]) adjusted for confounders. Adding possible underlying pathways did not explain these associations. Conclusions: Age‐related features (the presence of physical and cognitive frailty) contribute to the increased mortality risk in late‐life depression. Future studies in depressed older patients should study the additional value of a clinical geriatric assessment and integrated treatment aimed to at reduce frailty and ameliorate their mortality risk. Key points: Ageing related features (the presence of physical and cognitive frailty) contribute to the increased mortality risk in late life depressionDepressive symptom severity may not be independent related to the mortality in late‐life depression.Geriatric interventions aimed at reducing frailty in late life depression may ameliorate the mortality risk. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What is the prevalence of Hoarding Disorder (HD) in Late Life Depression (LLD) and do hoarding symptoms in LLD contribute to greater executive dysfunction, disability, and poorer depression treatment response? • What is the main finding of this study? HD concurrence with LLD is common at 30.1%, which is higher than HD comorbidity with obsessive-compulsive disorder (≤18%) or HD prevalence in the general population of older adults (6%). Hoarding symptoms concurrent with LLD were associated with greater executive dysfunction, disability, and poorer response to depression treatment. • What is the meaning of the findings? Individuals with HD and LLD may be at greater risk for cognitive and functional decline, thus underscoring the need for increased screening of hoarding symptoms in LLD and tailored interventions for individuals with both conditions. Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD. Cross-sectional. Outpatient psychiatry program. Eighty-three community-dwelling adults ages 65–90 with LLD. Problem-solving therapy. Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson's chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity. 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X2 (1)=4.0, p = 0.045; Stroop-Interference, X2 (1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t [70] = −2.1, β = −0.05, p = 0.044), Digit-Span (t [71] = −2.4, β = −0.07, p = 0.019), Letter-Fluency (t [ 71] = −2.8, β = −0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X2 [1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t [72] = 2.97, β = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X2 (1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t (67) = −2.15, β = −15.6, p = 0.035. We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group. [ABSTRACT FROM AUTHOR]

Abstract Aims Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. Methods We analysed longitudinal data of depression- and dementia-free individuals aged 60+ years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. Results The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6 years [SD, 4 years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose–response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). Conclusions Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

BackgroundCognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear.ObjectiveTo evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden.MethodsParticipants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden.ResultsLLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND.ConclusionLLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

Background : The present study aimed to synthesize the effects of five types of child maltreatment (physical abuse, emotional abuse, sexual abuse, physical neglect and emotional neglect) on late-life depression. Method : Four English-language databases (Web of Science, PsycINFO and PsycARTICLES, PubMed, and Cochrane Library) and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Weipu Database) were systematically reviewed, and data related to the association between child maltreatment and late-life depression were extracted. Ten studies involving 30,308 older adults were included, and the effect sizes were pooled using random-effect models. Findings : Except for sexual abuse, four types of child maltreatment were found to be positively associated with late-life depression. Physical abuse, emotional abuse and physical neglect were associated with elderly depression (PA: OR = 1.73, 95% CI = 1.55–1.95, p <.001; EA: OR = 1.92, 95% CI = 1.73–2.12, p <.001; PN: OR = 2.05, 95% CI = 1.15–3.67, p <.01) at a small level, and emotional neglect was associated with elderly depression (OR = 3.25, 95% CI = 1.43–7.39, p <.001) at an approximately moderate level. Gender moderated the relationship between physical neglect, emotional neglect, and late-life depression. Conclusion : Our findings highlight the significance of child maltreatment in the development of late-life depression, and underscore the need for future research and practice to explore potential ways to address late-life depression among older adults who suffered child maltreatment. [ABSTRACT FROM AUTHOR]

Maria Devita,1,2 Rossella De Salvo,1 Adele Ravelli,2 Marina De Rui,2 Alessandra Coin,2 Giuseppe Sergi,2 Daniela Mapelli1 1Department of General Psychology (DPG), University of Padua, Padua, Italy; 2Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, ItalyCorrespondence: Maria Devita, Department of General Psychology, Via Venezia 8, Padua, 35128, Italy, Tel +390498218949, Email maria.devita@unipd.itAbstract: Depression is one of the most common mood disorders in the late-life population and is associated with poor quality of life and increased morbidity, disability and mortality. Nevertheless, in older adults, it often remains undetected and untreated. This narrative review aims at giving an overview on the main definitions, clinical manifestations, risk and protective factors for depression in the elderly, and at discussing the main reasons for its under/misdiagnosis, such as cognitive decline and their overlapping symptomatology. A practical approach for the global and multidisciplinary care of the older adult with depression, derived from cross-checking evidence emerging from the literature with everyday clinical experience, is thus provided, as a short and flexible “pocket” guide to orient clinicians in recognizing, diagnosing and treating depression in the elderly.Keywords: late-life depression, older adults, mood disorders, geriatric depression

Background: Octogenarians of today are better educated, and physically and cognitively healthier, than earlier born cohorts. Less is known about time trends in mental health in this age group. We aimed to study time trends in the prevalence of depression and psychotropic drug use among Swedish 85-year-olds. Methods: We derived data from interviews with 85-year-olds in 1986–1987 (N = 348), 2008–2010 (N = 433) and 2015–17 (N = 321). Depression diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders. Symptom burden was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Information on psychotropic drug use, sociodemographic, and health-related factors were collected during the interviews. Results: The prevalence of major depression was lower in 2015–2017 (4.7%, p < 0.001) and 2008–2010 (6.9%, p = 0.010) compared to 1986–1987 (12.4%). The prevalence of minor depression was lower in 2015–2017 (8.1%) compared to 2008–2010 (16.2%, p = 0.001) and 1986–1987 (17.8%, p < 0.001). Mean MADRS score decreased from 8.0 in 1986–1987 to 6.5 in 2008–2010, and 5.1 in 2015–2017 (p < 0.001). The reduced prevalence of depression was not explained by changes in sociodemographic and health-related risk factors for depression. While psychoactive drug use was observed in a third of the participants in each cohort, drug type changed over time (increased use of antidepressants and decreased use of anxiolytics and antipsychotics). Conclusions: The prevalence of depression in octogenarians has declined during the past decades. The decline was not explained by changes in known risk factors for depression. The present study cannot answer whether changed prescription patterns of psychoactive drugs have contributed to the decline. [ABSTRACT FROM AUTHOR]

Late life depression (LLD) is an emerging challenge, and recognized as a significant barrier to long-term healthy aging. Viewed within the context of the medical/biological model, advances in brain sciences over the last several decades have led to a deeper understanding of the biology of LLD. These advances in current knowledge include the description of aging brain pathophysiology; the biology and biochemistry of neurotransmitters; the correspondence between changes in neurological structure, function, and neural network; the description of neural, hormonal and inflammatory biomarkers; and identification of typical phenotypic subtypes of LLD. Despite these advances, current treatment of LLD, which remains largely pharmacological with accompanying cognitive and behavioral interventions, has poor success rate for long-term remission among older people. A wider perspective, in keeping with several emerging aging concepts, is suggested as an alternative framework within which to view LLD. A growing body of research supports the important role in LLD of frailty, resilience, intrinsic capacity, and functional integrity. Similarly, important social determinants need to be addressed in the etiology of LLD, rooted largely in negative stereotypes of aging, with consequent repercussions of reduced participation and inclusion, growing social isolation, with loss of identity, meaning and hope. This perspective suggests the importance of a wider integrative conceptualization of depression, set against a background of emerging aging concepts.

The origins of late-life depression are multifaceted and remain challenging to fully understand. While the traditional monoamine neurotransmitter hypothesis provides some insights, it falls short in explaining the disease’s onset and progression, leaving treatments often less than optimal. There is an emergent need to uncover new underlying mechanisms. Among these, the “inflammation hypothesis” has been gaining traction in scientific discussions regarding late-life depression. There is compelling evidence linking inflammation processes to the emergence of this form of depression. This review delves into the nuanced relationship between inflammation and late-life depression, emphasizing the pivotal role and implications of inflammation in its pathogenesis. Changes in Ca2+ homeostasis, cytokine levels, brain-derived neurotrophic factor (BDNF), white cell ratios, and the involvement of the NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome have all been suggested as potential biomarkers that tie inflammation to late-life depression. Furthermore, factors such as aging-induced DNA damage, oxidative stress, mitochondrial impairments, disruptions in the hypothalamic-pituitary-adrenal axis, activated microglia and associated neuroinflammation, as well as the gut-brain axis dynamics, could serve as bridges between inflammation and depression. Deepening our understanding of these connections could usher in innovative anti-inflammatory treatments and strategies for late- life depression.

ObjectiveUse latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.MethodNeuropsychological assessment data from 121 participants in the Alzheimer's Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.ResultsA two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.ConclusionLCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a widely available treatment for major depression, but its efficacy and tolerability are uncertain for patients with late-life depression (LLD). To assess the existing evidence of rTMS for LLD treatment, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) according to PRISMA guidelines.Methods: We retrieved RCTs from four databases published between 1 January 2000 and 10 September 2021 comparing the effects of active and sham stimulation in LLD patients. We performed subgroup analyses to examine the impact of different parameters. The primary outcomes were the response and discontinuation rates of rTMS for LLD patients, representing for efficacy and tolerability, respectively. Secondary outcomes were remission and dropout rates. Discontinuation referred to patients who withdrew for any reason, while dropout referred to participants who withdrew early because of adverse events.Results: Nine articles describing 11 studies (two articles each contained two studies) met the eligibility criteria. All outcomes were analyzed using a random-effects model. The summary analysis of nine suitable RCTs revealed a cumulative response rate of 2.86 (95 % confidence interval (95 % CI), 1.87-4.37) and a remission rate of 4.02 (95 % CI, 1.83-8.81) in the active group compared to the sham group. The pooled odds ratios (ORs) for discontinuation and dropout rates were not significantly different between the two groups. In addition, some rTMS parameters were associated with better efficacy.Conclusions: The meta-analysis suggested that rTMS is an effective, well-tolerated treatment for patients with LLD. Future efforts should enhance study methodologies to improve their efficacy and increase the homogeneity of rTMS parameters to promote comparability between studies. [ABSTRACT FROM AUTHOR]

Introduction: Executive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD. Methods: Seventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target. Results: A total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post-intervention change in mean Montgomery-Asberg-depression scores was not different between iTBS or sham, p = 0.33. No significant group-by-time interaction for Montgomery-Asberg Depression rating scale scores (F3, 44 = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F1, 14 = 0.02, p = 0.88), Dimensional-change-card-sort scores F1, 14 = 0.25, p = 0.63, and working memory scores (F1, 14 = 0.98, p = 0.34). The Group-by-time interaction effect for functional connectivity (FC) within the Fronto-parietal-network was not significant (F1, 14 = 0.36, p = 0.56). No significant difference in the effect-of-time between the two groups was found on FC within the Cingulo-opercular-network (F1, 14 = 0, p = 0.98). Conclusion: Bilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement. [ABSTRACT FROM AUTHOR]

Objective: In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance.Design: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals.Results: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression.Conclusion: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging. [ABSTRACT FROM AUTHOR]

ObjectiveCognitive impairment associated with late-life depression can persist after remission of mood symptoms. Apathy, a common symptom of late-life depression, often leads to worse clinical outcomes. We examined if severity of apathy mediates cognitive difficulties in a cohort of older adults with major depression.MethodsOne hundred thirty-eight older adults with depression (54.4% female; mean [SD] age: 69.7 [7.4] years; mean [SD] education:15.6 [2.7] years) were recruited to participate in a treatment study, and only baseline data were analyzed. All participants received a comprehensive evaluation of depression, apathy, and cognition. We examined whether apathy mediated the relationship between depression and cognition, focusing our attention on memory and cognitive control. We then explored whether the mediation effects differed across women and men.ResultsIncreased apathy was significantly associated with worse depression and lower performance in the cognitive control domain but not in memory. Higher depressive scores were significantly associated with worse cognitive control but not memory. Mediation analyses revealed a significant indirect effect on cognitive control by depression through increased apathy scores with the mediator accounting for 21% of the total effect. Stratifying by sex, we found that women exhibited a significant indirect effect, with the mediator accounting for 47% of the total effect, whereas there was no mediation by apathy in men.ConclusionsThe findings imply that increased apathy mediates the relationship between cognition and depression. The identification of mediating effects may inform future treatment strategies and preventive interventions that can focus on decreasing apathy to improve cognition in late-life depression.

Background: Late life depression (LLD) refers to major depressive disorder (MDD) in adults over 65 years. LLD is associated with high morbidity and poor treatment outcomes. Transcranial direct current stimulation (tDCS) is a novel treatment for MDD. Efficacy in LLD though is unclear. Our aim was to investigate tDCS efficacy by pooling randomised controlled trials (RCT) in an individual participant data meta-analysis. Methods: Databases were searched for sham controlled RCTs of tDCS in MDD and bipolar depression. Individual participant data (IPD) were requested. Primary outcome was change in depressive symptoms. Bayesian multilevel modelling meta-analysis was conducted with individual participants nested within studies. Results: 6 RCTs were eligible, consisting of 43 participants (22 women), mean age 69.2 years. Active anodal tDCS over left dorsolateral prefrontal cortex (n = 19) was associated with an improvement in depressive severity, effect size 0.14 (95% credible interval [-0.44;0.15]) as compared to sham tDCS, which was not statistically significant. There was an 82% probability that tDCS treatment has a modest but non-null effect in improving depressive symptoms. Acceptability was high with no significant differences in discontinuation rates between active and sham groups. Limitations: The total sample size was small, limiting power. Discussion: In LLD, tDCS demonstrates a modest but non-null effect in improving depressive symptoms. Acceptability was high as measured by discontinuation rates. tDCS is a potential novel treatment option in LLD, though large scale RCTs in LLD are required to investigate this important clinical application.

Objectives: Previous studies regarding the relationship between depression and Alzheimer's neuropathology in older adults without dementia have reported conflicting findings. This study examined whether depression is associated with Alzheimer's neuropathology and whether sex moderates these relationships.Methods: This is a cross-sectional study of older adults without dementia (normal cognition or mild cognitive impairment, age 50+; CDR ≤ 0.5) who had autopsy within 1 year of their last clinic visit in the National Alzheimer's Coordinating Center database (2005-2020). Logistic regression models were fitted to determine if a recent or remote history of depression was associated with amyloid spread beyond the neocortex measured by modified Thal phase score, density of amyloid plaques measured by CERAD score or tau neuropathology measured by modified Braak score. A moderator analysis was performed to determine if any of these associations were moderated by sex.Results: This study included 407 participants (96 Thal, 405 Braak, and 406 CERAD). Those who had recently active depression (within previous 2 years) but not remote depression only were more likely to have higher Thal phase score compared to those without a history of depression (OR = 3.74; 95% CI, 1.15-12.17; p = 0.028). Sex did not moderate this association. No significant associations between recent depression and Braak or CERAD scores were observed.Conclusion: Our findings indicate that the association between late life depression and Alzheimer's neuropathology is associated with spread of amyloid pathology beyond the neocortex to include allocortical and subcortical regions critical for regulation of mood and motivated behavior. [ABSTRACT FROM AUTHOR]

Background: Reports on the efficacy of omega-3 fatty acids (n-3 PUFAs) for the treatment of late-life depression (LLD) are mixed, and most studies focus on the modification of depressive symptoms rather than depression prevention. The aim of the present study was to investigate the efficacy of n-3 PUFAs in preventing depressive recurrence in patients with late-life depression. In addition, we investigated the effects of n-3 PUFAs on changes in depressive and anxiety symptoms and inflammatory markers in LLD., Methods: A 52-week, double-blind, randomized, controlled trial was conducted. We enrolled a total of 39 euthymic patients with LLD. They were randomized to receive either n-3 PUFAs (1.2 g per day of eicosapentaenoic acid and 1 g of docosahexaenoic acid) or placebo for 52 weeks. Recurrence of depression and severity of depression symptoms were assessed at baseline and weeks 4, 8, 16, 24, 32, 40, and 52., Results: A total of 39 patients completed the trial with 19 in the n-3 PUFAs group and 20 in the placebo group. Cox proportional hazard regression indicated that n-3 PUFAs had significant protective effect on depression recurrence (Hazard Ratio: 0.295, 95 % Confidence Interval: 0.093-0.931, p value =0.037). But n-3 PUFAs intervention had no significant effect in reducing depressive or anxiety symptoms, inflammatory markers over the placebo group., Limitation: The results should be interpreted with consideration of the modest sample size., Conclusion: These findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary., Competing Interests: DISCLOSURES During the past 2 years JCN has received research support from National Institute of Mental Health; consultation fees from Biohaven, Clexio, Johnson and Johnson, Novartis, and Otsuka; and royalties from UpToDate. JG reports no conflicts with any product mentioned or concept discussed in this article. RSM has received research support from the National Institute of Mental Health, National Institute of Aging, Johnson and Johnson, and Janssen Research and Development LLC., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: Accumulating evidence suggests that hearing loss (HL) treatment may benefit depressive symptoms among older adults with Major Depressive Disorder (MDD), but the specific individual characteristics of those who stand to improve most are unknown.Methods: N = 37 patients ≥60 years with HL and MDD received either active or sham hearing aids in this 12-week double-blind randomized controlled trial. A combined moderator approach was utilized in the analysis in order to examine multiple different pretreatment individual characteristics to determine the specific qualities that predicted the best depressive symptom response to hearing aids. Pretreatment characteristics included: Hearing Handicap Inventory for the Elderly (HHIE-S), pure tone average (PTA), speech reception threshold (SRT), Short Physical Performance Battery (SPPB), cognition (Repeatable Battery for the Assessment of Neuropsychological Status).Results: The analysis revealed a combined moderator, predicting greater improvement with active versus sham hearing aids, that had a larger effect size than any individual moderator (combined effect size [ES] = 0.49 [95% CI: 0.36, 0.76]). Individuals with worse hearing-related disability (HHIE-S: individual ES = -0.16), speech recognition (SRT: individual ES = -0.14), physical performance (SPPB: individual ES = 0.41), and language functioning (individual ES = 0.19) but with relatively less severe audiometric thresholds (PTA: individual ES = 0.17) experienced greater depressive symptom improvement with active hearing aids.Conclusions: Older adults with relatively worse HL-related, physical, and cognitive functioning may stand to benefit most from hearing aids. Given the large number of older adults experiencing HL and MDD, a non-invasive and scalable means of targeting those most likely to respond to interventions would be valuable. [ABSTRACT FROM AUTHOR]

Objectives: Recent research has revealed important neural and psychiatric consequences of hearing loss (HL) in older adults. This pilot study examined the neural effects of HL and the impact of hearing aids on neuropsychiatric outcomes in major depressive disorder (MDD).Design: Twelve-week, double-blind, randomized controlled trial.Participants/intervention: N = 25 (≥60 years) with MDD and moderate-profound HL were randomized to receive hearing aids (100% gain targets) or sham hearing aids (flat 30 dB HL) in addition to psychiatric treatment-as-usual.Measurements: Depressive symptoms (Hamilton Rating Scale for Depression [HRSD]), executive functioning (NIH Toolbox Flanker), integrity of auditory brain areas (structural MRI, diffusion tensor imaging).Results: At baseline, worse speech discrimination was associated with auditory cortical thinning (Left anterior transverse temporal gyrus: r = 0.755, p = 0.012) and lower integrity of the superior longitudinal fasciculus (FA: Left r = 0.772, p = 0.025, Right r = 0.782, p = 0.022). After 12-weeks, hearing aids were effective at improving hearing functioning (Hearing Handicap for the Elderly: active -12.47 versus sham -4.19, t = -2.64, df = 18, p = 0.016) and immediate memory (active +14.9 versus sham +5.7, t = 2.28, df = 16, p = 0.037). Moderate improvement was observed for hearing aids on executive functioning but did not reach statistical significance (Flanker: active +4.8 versus sham -2.4, t = 1.95, df = 15, p = 0.071). No significant effect on depression was found (HRSD: active -5.50 versus sham -7.32, t = 0.75, df = 19, p = 0.46).Conclusions: HL can affect brain regions important for auditory and cognitive processing, and hearing remediation may have beneficial effects on executive functioning in MDD. Future studies may evaluate whether impairment in cognitive control consequent to HL may be an important risk mechanism for MDD. [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved. Methods This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function. Discussion The main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT. Trial registration ClinicalTrials.gov Identifier: NCT03849417 , 21/2/2019.

Objectives: We studied sociodemographic and health factors associated with depression across three age groups of community‐dwelling older adults. Methods/Design: We used data from 16,785 participants from the third follow‐up of the Singapore Chinese Health Study (mean age: 73, range: 61‐96 years). We defined depression as having a score of ≥5 using the 15‐item Geriatric Depression Scale. We used regression splines to examine the pattern of depression risk with age and applied multivariable logistic regression to study factors associated with depression. Results: Increasing age was associated with depression in an inverted J‐shape relationship with the highest odds ratio (OR) at age 75. Compared to the youngest‐old (<70 years), the middle‐old (70‐80 years) had higher odds of depression [OR = 1.20, 95% confidence interval (CI) = 1.09–1.31], while the oldest‐old (>80 years) had no increased risk (OR = 1.01, 95% CI = 0.89–1.15). We also found demographic (men, lower education, unemployment), social (living alone, poor social support, no social activity) and health factors (instrumental limitations, poor physical function, function‐limiting pain, chronic diseases, cognitive impairment, poor sleep quality, poor self‐rated health) associated with depression. In stratified analysis by age groups, the OR estimates for lower education level, instrumental limitations and cognitive impairment decreased with age, whereas the risk of depression for men increased with age (all p‐values for interaction<0.03). Conclusions: Compared to the youngest‐old, the likelihood of depression was highest among middle‐old adults and decreased to null in the oldest‐old. The associations between some factors and depression were attenuated with age, suggesting a coping mechanism among oldest‐old survivors. Key points: Older adults around the age of 75 years had the highest likelihood of depression compared to their younger or older counterparts.The associations of depression with instrumental limitations and cognitive impairment were attenuated with increasing age, while the odds of depression in men compared to women were higher with increasing age.We recommend that interventions addressing depression among older adults in the community should focus on older adults between the ages of 70 and 80, while recognizing the higher risk in men aged 80 and above. [ABSTRACT FROM AUTHOR]

Hua Xu,1,2 Diana Koszycki2,3 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Faculty of Education and Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 3Institut du Savoir Montfort, Hôpital Montfort, Ottawa, Ontario, CanadaCorrespondence: Hua Xu; Diana Koszycki Email xuhuaemail@126.com; dkoszyck@uottawa.caAbstract: Interpersonal psychotherapy (IPT) is a time-limited, structured, interpersonally oriented psychotherapy, with demonstrated efficacy for the treatment of major depression across the lifespan. IPT uses a medical model of illness and links depressed mood to four research-informed interpersonal problem areas: complicated grief, role transitions, role disputes, and interpersonal deficits/sensitivity. The IPT model of vulnerability to depression nicely dovetails with interpersonal issues that are faced by older adults, and this article focuses on the application of IPT for late-life depression in China. The group format of IPT may be a practical and efficient method of improving access to an established depression-focused treatment for China’s rapidly aging population and has the advantage of providing important social support for patients who feel lonely, isolated, and stigmatized. Short-term interventions like IPT are more cost-effective from a public health perspective and can easily be delivered in primary care facilities, where many elderly patients receive care. IPT is effective in different cultures, and possible cultural adaptations of IPT for older adults in China are discussed herein.Keywords: interpersonal psychotherapy, late-life depression, cultural adaptation, China

Background: This is the PhD thesis protocol of an ongoing study entitled 'Effect of Psychoeducation on short- term outcome in patients with Late Life Depression: A Randomized Control Trial'. Psychoeducation is a proof-based therapeutic intervention for patients and their caretakers/family members that provides plenty of information and support for better understanding and coping up with the illness, which is being diagnosed. Aim: The aim is to examine the effect of psychoeducation on short- term outcome in patients with late life depression. Hypothesis: The hypothesis is that psychoeducation will improve outcome in patients with late life depression at 4 weeks. The sample size is 154. Material and Methods: The methodology is that patients aged 60 years and above coming to Out Patient Department (OPD) of the Department of Geriatric Mental Health, King George's Medical University and having the first episode of depression, which has been clinically diagnosed, will be taken. Then, Mini International Neuropsychiatric Interview (MINI) 6.0.0 will be applied for the confirmation of diagnosis. After confirmation, Hindi Mental Status Examination (HMSE) will be done to know the cognitive status, those scoring 24 and above on HMSE will be included in the study. The included patients will be evaluated on Hamilton Depression Rating Scale (HAM-D), Geriatric Depression Scale (GDS) and Knowledge Attitude Experience (KAE) Questionnaire. Next, the patients will be randomized in case group and control group. Case group will be given intervention of 'psychoeducation' through a video, and control group will be given 'placebo' through a video. For both the groups, the first follow up termed as 'booster session' will be at 2 weeks +/- 4 days from the baseline and second follow up will be at 4 weeks +/- 4 days from the baseline. Statistical Analysis: Data will be recorded on the spreadsheet and the results will be analyzed using the statistical software.

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects., Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies., Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004)., Conclusion: msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Background: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT.Methods: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time.Results: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA).Conclusion: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations. [ABSTRACT FROM AUTHOR]

To longitudinally examine the latent statuses of depressive symptoms and their association with cognitive impairment in older U.S. nursing home (NH) residents. Using Minimum Data Set 3.0, newly-admitted, long-stay, older NH residents with depression in 2014 were identified (n = 88,532). Depressive symptoms (Patient Health Questionnaire-9) and cognitive impairment (Brief Interview of Mental Status) were measured at admission and 90 days. Latent transition analysis was used to examine the prevalence of and the transition between latent statuses of depressive symptoms from admission to 90 days, and the association of cognitive impairment with the statuses at admission. Four latent statuses of depressive symptoms were identified: 'Multiple Symptoms' (prevalence at admission: 17.3%; 90 days: 13.6%), 'Depressed mood' (20.0%; 19.5%), 'Fatigue' (27.4%; 25.7%), and 'Minimal Symptoms' (35.3%; 41.2%). Most residents remained in the same status from admission to 90 days. Compared to residents who were cognitively intact, those with moderate impairment were more likely to be in 'Multiple Symptoms' and 'Fatigue' statuses; those with severe impairment had lower odds of belonging to 'Multiple Symptoms', 'Depressed Mood', and 'Fatigue' statuses. By addressing the longitudinal changes in the heterogeneous depressive symptoms and the role of cognitive impairment, findings have implications for depression management in older NH residents. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD).Methods: Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment.Results: Frail individuals (n = 49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (n = 51 with 0-2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (t = 2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail.Conclusion: Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) and cognitive impairments are both common in patients with late-life depression (LLD). However, the relationship between NPS and cognitive functions in LLD patients remains unclear. The current study aims to explore the effects of NPS on cognitive impairments in LLD patients.Methods: Two hundred and sixty-two LLD patients and 141 normal controls (NC) were recruited. Exploratory factor analysis was used to extract factors from the Neuropsychiatric Inventory (NPI). Correlation, mediation, and moderation analyses were used to explore whether NPS exacerbated the cognitive impairments in LLD and whether NPS exhibited different effects on cognitive impairments in acute-state LLD (aLLD) and recovery-state LLD (rLLD).Results: Three main factors were extracted from the NPI, including emotional, behavioral, and psychotic factors. The patients with LLD exhibited worse cognition and higher NPI scores, and the scores of NPI-total and three extracted factors were negatively associated with cognitive scores. The mediation analyses exhibited that NPI-total and behavioral factor scores increase the difference in cognition scores between LLD and NC groups. The mediation analyses exhibited that behavioral factor score played a greater effect on impairing MMSE in the rLLD group than in the aLLD group. Additionally, behavioral factor score was in a trend to be negatively associated with Mini-Mental State Examination (MMSE) score changes at a one-year follow-up (p = 0.051).Conclusions: NPS, especially behavioral symptoms, exacerbate cognitive impairments in LLD and may contribute to residual cognitive impairment in rLLD patients. Early intervention for behavioral symptoms in LLD patients may be beneficial to their long-term clinical prognosis.

Objective: Slowed processing speed and executive dysfunction are associated with poor outcomes in Late Life Depression (LLD), though it is unclear why. We investigated whether these variables interfere with the development of positive treatment expectancies in an antidepressant trial.Methods: Depressed older subjects were randomized to Open (intended to increase patient expectancy) or Placebo-controlled (termed 'Hidden,' intended to decrease expectancy) administration of antidepressant medication for 8 weeks. Analysis of covariance analyzed the between-group difference on expectancy (Credibility and Expectancy Scale [CES]) and depression (Hamilton Rating Scale for Depression [HRSD], Clinical Global Impressions [CGI] Severity). Moderator analyses examined whether these Open versus Hidden differences varied based on higher versus lower processing speed and executive function.Results: Among the 108 participants, a significant between-group difference was observed on expectancy (effect size [ES, Cohen's d] = 0.51 on CES Item 2; ES = 0.64 on Item 4), indicating the manipulation was effective. Processing speed as measured by the Stroop Color-Word Test (number color-words named in congruent condition) was a significant moderator of the Open versus Hidden effect on expectancy. Depressive symptom improvement was greater on average for Open versus Hidden participants who received active drug (CGI-severity ES = 1.25, HRSD ES = 0.41), but no neurocognitive moderators of the between-group difference reached statistical significance.Conclusions: Slowed processing speed impairs the development of expectancies in antidepressant trials for LLD, which may help explain lower antidepressant response among older adults. Future studies may address whether interventions to optimize treatment expectancies are capable of improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: In the last decade, repetitive transcranial magnetic stimulation (rTMS) has been introduced as a non‐invasive neuromodulation therapy for depression. Little is known, however, about (serious) adverse events (AE) of rTMS in older adults with a depression. In this article, we want to study what is known about (serious) AE of rTMS in older adults (>60 years) with late‐life depression (LLD). Methods: A systematic search has been performed according to the PRISMA guidelines in PubMed, EMBase and PsycInfo. We have screened 622 articles for eligibility. Eleven studies, evaluating 353 patients in total, were included in this review. Results: AE were reported in 12.4% of the older adults with a LLD treated with rTMS, serious AE in 1.5%. Headache (6.9%) and discomfort at the stimulation site (2.7%) are the most commonly reported AE. Serious AE reported are: psychiatric hospitalization (three times), a combination of posterior vitreous detachment and retinal tear, and increased suicide ideation (both once). Conclusions: rTMS in older adults with LLD was concluded overall to be safe due to the low frequency of AE reported in trials and observational studies. In case‐reports, however, more serious AE have been described. To tailor use of rTMS in older adults with LLD, more research is needed in larger samples to optimize tolerance. Highlights: Little is known about (serious) AE of rTMS in older adults (>60 years) with LLD.A relatively low percentage of AE (12.4% in total) and serious AE (1.5% in total) in response to rTMS occurs in older adults with LLD.rTMS is a safe and well‐tolerated treatment option for older adults with LLD. [ABSTRACT FROM AUTHOR]

Frailty and disability are commonly found in Late Life Depression (LLD) and have been associated with increased depression severity, health comorbidities and mortality. Additionally, physical frailty has been associated with suicide in later life, independent of presence of a mood disorder. The objective of our study was to assess the associations of physical frailty and functional disability with suicidal ideation, controlling for depression severity and demographic factors, in an older depressed sample. This study used data from community-dwelling older adults with major depression. Eligible participants were ≥ 65 years old, completed measures of depression symptom severity (Hamilton Depression Rating Scale-24 item; HDRS-24), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and physical frailty/functional capacity measures. Participants were 88 older adults with a mean age of 71.5 (SD = 6.0) and 66% of the sample was female. Poorer performance on frailty measures of gait speed (B =.239, p =.003) and muscle weakness (B = −.218, p =.01) were significantly associated with higher levels of suicidal ideation, independent of depression severity and demographic factors. Functional disability was also significantly related to suicide ideation, specifically impairment in financial capacity (B = −.290, p =.008), social interaction (B =.408, p <.001), and communication skills (B =.373, p =.001). Our findings show that, in LLD, frailty and functional disability are significantly associated with higher levels of suicide ideation, independent of depression symptom severity. [ABSTRACT FROM AUTHOR]

Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis.Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants.Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (Pauc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (Pauc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, Pfdr = 0.0744 & P = 0.0004, Pfdr = 0.0744).Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD.

The article discusses a study about the use of hearing aids as a therapeutic agent for major depressive disorder among older adults with hearing loss.

Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis. Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants. Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (P auc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (P auc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, P fdr = 0.0744 & P = 0.0004, P fdr = 0.0744). Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved. Methods: This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function. Discussion: The main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT. Trial registration: ClinicalTrials.gov Identifier: NCT03849417, 21/2/2019. [ABSTRACT FROM AUTHOR]

BackgroundLate life depression (LLD), a common mental disorder, has become an increasingly acute public health concern with a quickly expanding geriatric population worldwide. To our knowledge, however, the incidence of LLD in northern cities in China has not been empirically investigated, and many elderly people with depressive moods and mild depressive symptoms have not been given sufficient attention.Methods/DesignThis is a multi-stage and prospective study. The first stage is a cross-sectional study, investigating the epidemiological characteristics of LLD in northern China and exploring the biological, psychological, and social risk factors for developing LLD based on a set of questionnaires from 6,800 community-residing elderly adults. The second stage involves statistical analysis, by constructing a risk factor model for LLD and analyzing their direct and indirect functional routes on the basis of structural equation modeling. The third stage is an experimental study a total of 60 elderly patients with LLD and their principle caregivers will be randomly assigned to control and trial groups. The trial group patients and caregivers will undergo supportive psychosocial, drug treatment, and health education (PDH) intervention, whereas the control group patients and caregivers will be treated routinely (treatment as routine, TAR, which includes drug treatment and health education). At the end of the intervention, depressive symptoms, quality of life, and the social and cognitive functioning of the patients in the two groups will be respectively assessed at a baseline and after 6, 9, and 12 months post-intervention by employing scales and questionnaires to analyze the effectiveness of the supportive PDH intervention measures in comparison with TAR. Ultimately, a supportive PDH intervention and health management model will be obtained by combining PDH intervention with mental health institutions, community health services, and aging families as the main line.DiscussionThis study will provide strong and suitable evidence for enhancing the integrated supportive PDH intervention and health management model of LLD patients among community-dwelling residents.EthicsThis study has been approved by the Ethics and Research Committee of the First Affiliated Hospital of China Medical University (approval No. [2019] 2019-312-2).

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.