Treatment Of Late-life Depression Research Articles

Feasibility and Acceptability Findings From a Pilot Study of the Adapted Ziba Ufa Intervention for Late Life Depression and Chronic Conditions in Tanzania

ObjectiveTo conduct a pilot study of the adapted Ziba Ufa intervention for the treatment of late life depression, to assess feasibility and acceptability. DesignA pilot clinical trial, using a single group design over eight months, using qualitative and quantitative methods. SettingFour rural and urban outpatient health clinics in Kilimanjaro, Tanzania. ParticipantsIndividuals aged 60 years and above, with chronic health conditions and mild-moderate depression symptoms, with no cognitive impairment or severe frailty. Intervention‘Ziba Ufa’ (‘Repair the Crack’) was adapted for Tanzania from the Depression in Late Life (DIL) intervention. It is a hybrid model of problem-solving therapy and healthy lifestyle advice. MeasurementsA locally validated depression screener (MOSHI-D) was used to screen for mild-moderate depression symptoms. Feasibility was assessed using recruitment and retention data, and acceptability was assessed using thematic analysis and the Theoretical Framework of Acceptability to analyze exit interviews with participants and counsellors at follow-up. ResultsA total of 157 older adults were screened, and thirty-two participants were enroled, with eight allocated to one counsellor per site. The enrolment rate of those clinically eligible at screening was 52%, with the majority unable to attend due to living too far away from the clinic. The retention rate was high at 97% (N=31). Qualitative feedback indicated the programme was acceptable because it helped older adults ‘open up’ and did not interfere with everyday life. ConclusionsZiba Ufa was feasible and acceptable in Tanzania when delivered in routine clinical settings, with travel reimbursed.

Efficacy of problem-solving therapy in treating late-life depression with potential cognitive impairment: a systematic review and meta-analysis.

Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings. The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital. CRD42023473782.

The N-3 polyunsaturated fatty acids supplementation to prevent depression recurrence in patients with late-life depression: A 52-week double-blind, placebo-controlled trial

BackgroundReports 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. MethodsA 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. ResultsA 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. LimitationThe results should be interpreted with consideration of the modest sample size. ConclusionThese findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD.

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

BackgroundLate-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. ObjectiveThis study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. MethodsA 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. ResultsThe ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. ConclusionThe combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition

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.

Experts Advise How to Maximize Treatment of Late-Life Depression

Experts Advise How to Maximize Treatment of Late-Life Depression

17. Predictors of Remission After Repetitive Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression

17. Predictors of Remission After Repetitive Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression

Research status and global trends of late-life depression from 2004 to 2023: bibliometric analysis.

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

Translating Research into Practice: Useful Scientific Advances in the Prevention and Treatment of Late-Life Depression, Bipolar Disorder, and Anxiety to Help Get Your Patients Well

To address the gap between science and implementation, the presenters, international known for their work in late-life mood and anxiety disorders, will contextualize advances in clinical care and provide the audience with advice about how to implement emerging evidence into their clinical programs.Dr. Okereke will provide an overview of the framework of prevention science developed by the National Academy of Medicine. This framework includes indicated, selective, and universal approaches to prevention, and provides a set of guiding principles for developing and applying interventions to prevent depression. She will address prevention trials targeting changes in nutritional, behavioral, and lifestyle factors which may play an important role in reducing the overall burden of depression in older adults.Dr. Gildengers will speak about Bipolar disorder in late-life and provide an overview of the International Society for Bipolar Disorders (ISBD) task force to advance healthcare for older adult bipolar disorder (OABD). This task force established the Global Aging & Geriatrics Experiments in Bipolar Database (GAGE-BD), an effort to combine international datasets into a unified database. GAGE-BD has facilitated research investigations in OABD, addressing a host of topics, including symptom severity in OABD, antipsychotic treatment, and long-term effects of lithium. Dr. Gildengers will review recent research in OABD focusing on reports from the ISBD task force on OABD and GAGE-BD and address the implications for treatment.Dr. Lenze will speak about depression treatment in late-life with a focus on both effectiveness of treatments as well as safety issues of particular relevance for late-life such as falls and cognitive health. He will describe how, over the past decade, several new studies have enhanced our knowledge about safety and effectiveness of antidepressant strategies and share how it is now possible to advance a treatment algorithm based on an understanding of the benefits and risks of antidepressant monotherapies and augmentation strategies. This algorithm includes starting with simple straightforward medications (SSRIs, mirtazapine), then to more complex multi-modal medications (SNRIs, vortioxetine) and then to augmentation strategies (aripiprazole) and interventional strategies (ketamine, TMS, ECT). Dr. Lenze will present the evidence for these strategies and make recommendations about the place of each strategy in a treatment algorithm. He will also discuss the place of precision medicine in choosing an antidepressant based on an individual patient's phenotype.Dr. Andreescu will provide an update on late-life anxiety disorders. She will describe the relationship between anxiety syndromes and several major diseases of aging including cardiovascular, autoimmune diseases, and Alzheimer's Disease and related dementias. As anxiety disorders have the highest lifetime prevalence of any psychiatric illness, Dr. Andreescu will teach the audience how anxiety and its phenotypes potentially represent a highly prevalent and modifiable risk factor for diseases of aging. In this presentation, she will discuss the fluidity of anxiety phenotypes throughout the lifespan, current evidence-based treatment options, and emerging evidence for new treatments for late-life anxiety.Dr. Karp will integrate the main themes from each of the presentations into a call for action for future research and clinical care priorities. There will be ample time for audience engagement and discussion.

Complex antidepressant therapy with the inclusion of various neuroprotectors in inpatient gerontopsychiatric practice

IntroductionDepressions are the most common mental disorders in elderly and senile patients. In these patients, there is a decrease in neurotrophic potential. Treatment of such patients with antidepressants alone does not always allow to achieve complete normalization of the secretion of neurotrophic factors and complete restoration of neurogenesis processes. In this regard, it is important to expand therapeutic opportunities to develop new therapeutic strategies for pharmacotherapy of late-age depression.ObjectivesComparative evaluation of the effectiveness of two types of complex antidepressant therapy with the inclusion of different neuroprotectors (actovegin or cerebrolysin) in the treatment of late-life depression in the therapeutic regimen.MethodsThe study included 2 groups of patients with mild and moderate depressive episode (DE), comparable in basic demographic and clinical parameters.The 1st group included 21 people, including 7 men (33.3%) and 14 women (66.7%), median age were 69 years [66; 76]. In 10 patients (47.6%), DE was diagnosed as part of recurrent depressive disorder (DDR), in 9 patients (42.9%) - as part of bipolar affective disorder (BAR), and in 2 patients (9.5%) is a single DE. Group 2 included 20 patients, 5 of them men (25%) and 15 women (75%), median age were 64 years [62; 70]. In 11 patients (55%), DE was diagnosed as part of DDR, in 6 patients (30%) - as part of BAR, and in 3 patients (15%) – single DE.The 1st group of patients received complex antidepressant therapy with the inclusion of actovegin for one month, the 2nd group - with the inclusion of cerebrolysin. The effectiveness of the therapy was assessed on the HAMD-17 and HARS scales.ResultsA comparative study demonstrated the effectiveness of both types of complex antidepressant therapy used.A comparative assessment of the effectiveness of the therapeutic response in two groups of patients showed no statistically significant differences in the reduction of depressive disorders after 2 weeks of therapy. Only by the end of the therapeutic course there was a more pronounced reduction of depressive disorders in the 1st therapeutic group (73.6% vs 63.6% (p < 0.05)).Reduction of anxiety disorders, assessed on the HARS scale, was noted both by the 14th and 28th day of therapy in both therapeutic groups. However, it turned out to be more pronounced in the 1st therapeutic group: by the 14th day of therapy, the reduction of anxiety in the 1st and 2nd groups of patients was 36.4% and 30.0%, respectively (p < 0.05), and by the end of therapy - 77.7% and 60.0%, respectively (p < 0.01).ConclusionsThe augmentation of antidepressant therapy with drugs with multimodal activity, actovegin and cerebrolysin, should be considered as effective and it can be recommended for inclusion in the therapeutic regimen for the treatment of late-age depression in a psychiatric hospital.Disclosure of InterestNone Declared

Novel Approaches to Assessment and Treatment of Late-life Depression

Depression in late life is common and associated with suffering, reduced quality of life, increased risk of disability, cardiac, cerebrovascular, peripheral diseases, suicidality, all-cause mortality, and economic burden. Many older adults face significant access barriers to mental health services and often remain undiagnosed and untreated. When treatments are considered for late-life depression, antidepressants often have modest efficacy, and older adults prefer alternative approaches. Novel technologies including ecological momentary assessments using mobile devices and machine learning models, can guide the development of scalable and rapid assessments of late-life depression. Further, new therapeutic approaches, such as transcranial direct current stimulation and machine-learning guided psychotherapies, may improve efficacy and provide an alternative to existing therapies. In this session we will present three studies that leverage novel therapeutics and technologies to improve assessment and treatment of late-life depression. We will present findings of research studies in late-life depression and cognitive dysfunction, describe clinical implications. and discuss how findings can be implemented to improve the standard of care in community settings.

Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis.

The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function. A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis. Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low. Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.

Cost-effectiveness of behavioral activation compared to treatment as usual for depressed older adults in primary care: A cluster randomized controlled trial

IntroductionDepression in older adults is associated with decreased quality of life and increased utilization of healthcare services. Behavioral activation (BA) is an effective treatment for late-life depression, but the cost-effectiveness compared to treatment as usual (TAU) is unknown. MethodsAn economic evaluation was performed alongside a cluster randomized controlled multicenter trial including 161 older adults (≥65 years) with moderate to severe depressive symptoms (PHQ-9 ≥ 10). Outcome measures were depression (response on the QIDS-SR), quality-adjusted life-years (QALYs) and societal costs. Missing data were imputed using multiple imputation. Cost and effect differences were estimated using bivariate linear regression models, and statistical uncertainty was estimated with bootstrapping. Cost-effectiveness acceptability curves showed the probability of cost-effectiveness at different ceiling ratios. ResultsSocietal costs were statistically non-significantly lower in BA compared to TAU (mean difference (MD) -€485, 95 % CI -3861 to 2792). There were no significant differences in response on the QIDS-SR (MD 0.085, 95 % CI -0.015 to 0.19), and QALYs (MD 0.026, 95 % CI -0.0037 to 0.055). On average, BA was dominant over TAU (i.e., more effective and less expensive), although the probability of dominance was only 0.60 from the societal perspective and 0.85 from the health care perspective for both QIDS-SR response and QALYs. DiscussionAlthough the results suggest that BA is dominant over TAU, there was considerable uncertainty surrounding the cost-effectiveness estimates which precludes firm conclusions.

Effect of computerized cognitive training on mood, cognition, and serum brain-derived neurotrophic factor level in late-life depression - a pilot randomized controlled trial.

The aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels. A total of 28 community-living Chinese individuals aged 55-75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6 weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and follow-up. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level. Our sample had a mean age of 66.8 (SD = 5.3) years, a mean HAM-D score of 19.4 (SD = 7.5), and a mean PHQ-9 score of 18.0 (SD = 6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference = -5.5; p = 0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p < 0.001), MoCA (1.4 vs. -1.3; 2.7; p = 0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p = 0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level. With computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6 weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression. https://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029.

S12: Recent advances in therapies for late-life neuropsychiatric disorder

Symposium OverviewThis international symposium combining experts from Canada, Australia and the USA and supported by the American Association for Geriatric Psychiatry will present an update on the recent advances in therapeutic interventions for late life mood and cognitive disorders, including late life depression, anxiety and apathy associated with dementia, and preventive strategies including mind-body interventions. Four leaders of the field will present the summary of novel studies: starting with Dr. Benoit Mulsant (CA) presenting the results of the recently completed OPTIMUM study of novel strategies optimizing treatment of late-life treatment resistant depression. He will be followed by Dr. Krista Lanctot’ (CA) update on novel therapies for apathy associated with Alzheimer’s disease, and Dr Nancy Pachana (AU) will present on non-pharmacological approaches to treatment of anxiety associated with neurodegenerative disorders. Finally, Dr. Helen Lavretsky (USA) will present on the recent studies of mind-body therapies used to treat and prevent late life depression and cognitive decline, along with the discussion of the underlying neurobiological mechanisms. The panel will conclude with a brief discussion of future directions in the development of therapeutic interventions.Treatment-resistant depression in late life has been understudied and is lacking evidence supporting augmentation or switching strategies. Recently completed OPTIMUM multi-site study (funded by the PCORI) sought to compare effectiveness of augmentation strategies (bupropion or aripiprazole) to switch to bupropion, in the first step of 1-week acute treatment followed by randomization into the 2nd step of augmentation with Lithium or switch to nortriptyline. The augmentation strategies in the first step produced the most robust response compared to switching, and did not differ in the 2nd step. Primary outcomes included remission rates and wellbeing measures. A discussion of future directions will be provided at the end of this presentation.In those with Alzheimer’s disease, apathy is common and associated with decreased quality of life, increased risk of decline and increased mortality. As such, apathy is increasingly recognized as an important treatment target. Recent advances in diagnosis and treatment will be reviewed.In this presentation, several methodological issues will be discussed, such the importance and prevalence of apathy in Alzheimer’s disease (AD); current diagnostic criteria for apathy in neurocognitive disorders, and will present the results of recent pharmacologic interventions for apathy in AD.In this presentation, new focused and innovative treatments for anxiety in persons with Alzheimer's and Parkinson's disease with co-morbid anxiety will be discussed. Anxiety is common in Alzheimer's Disease and Parkinson's disease and contributes to increased disability and poorer quality of life. Yet only a small fraction of such patients received any form of treatment for mental health issues. Non-pharmacological approaches to address anxiety are advantageous in these populations. Research on tailored CBT and innovations such as virtual reality approaches for these groups will be discussed.Standard pharmacological therapies for treatment of late life depression offer limited efficacy with the downside of adverse events and drug-drug interaction. Novel strategies are needed for more effective and safe treatment and prevention strategies for mood and cognitive disorders in late life. This presentation will focus on the recently completed studies of Tai Chi for treatment of late life depression, and yoga for prevention of cognitive decline in older women at risk for Alzheimer’s disease. Neural and peripheral biomarkers of treatment response will be described. Future directions in mind-body therapies research will be outlined.

Improving social reward responsivity and social connectedness in psychotherapies for late-life depression: Engage & Connect as an example

Psychotherapies are effective in reducing late-life depression. Yet, about half of patients remain depressed at treatment end. Advances in neuroscience can inform simplified interventions that target key brain networks impacted by depression. Behavioral activation therapies that increase social connectedness may improve social reward responsivity and alter abnormalities of the Positive Valence System (PVS). Engage & Connect is an example for a scalable and simple neuroscience-informed psychotherapy, aimed to improve PVS functions and social reward responsivity by increasing engagement in rewarding social activities. Interventions that improve social reward responsivity can be promising first-line treatments for late-life depression in the community.

Late life depression and concepts of aging: an emerging paradigm.

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.

Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders.

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.

Brain morphometric features predict depression symptom phenotypes in late-life depression using a deep learning model.

Our objective was to use deep learning models to identify underlying brain regions associated with depression symptom phenotypes in late-life depression (LLD). Diagnosed with LLD (N = 116) and enrolled in a prospective treatment study. Cross-sectional. Structural magnetic resonance imaging (sMRI) was used to predict five depression symptom phenotypes from the Hamilton and MADRS depression scales previously derived from factor analysis: (1) Anhedonia, (2) Suicidality, (3) Appetite, (4) Sleep Disturbance, and (5) Anxiety. Our deep learning model was deployed to predict each factor score via learning deep feature representations from 3D sMRI patches in 34 a priori regions-of-interests (ROIs). ROI-level prediction accuracy was used to identify the most discriminative brain regions associated with prediction of factor scores representing each of the five symptom phenotypes. Factor-level results found significant predictive models for Anxiety and Suicidality factors. ROI-level results suggest the most LLD-associated discriminative regions in predicting all five symptom factors were located in the anterior cingulate and orbital frontal cortex. We validated the effectiveness of using deep learning approaches on sMRI for predicting depression symptom phenotypes in LLD. We were able to identify deep embedded local morphological differences in symptom phenotypes in the brains of those with LLD, which is promising for symptom-targeted treatment of LLD. Future research with machine learning models integrating multimodal imaging and clinical data can provide additional discriminative information.

Effect of prior pharmacotherapy on remission with sequential bilateral theta-burst versus standard bilateral repetitive transcranial magnetic stimulation in treatment-resistant late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes.