Participation in Physical, Cognitive, and Social Activities and the Association with Mobility Disability Transitions in Older Adults.

Development of late-life mobility disability is a dynamic process of transitions between worsening and improving. We tested associations between participation in physical, social, and cognitive activity with mobility disability transitions. Participants (N=2,758, age 78.1 years [SD: 7.7]) from two Rush Alzheimer's Disease Center cohorts completed annual mobility disability questionnaires for 7.6 (SD: 4.4) years. First-order Markov transition models tested associations between baseline self-reported physical, social, and cognitive activity with bidirectional transitions in mobility disability score increases (worsening) and decreases (improving) between consecutive visits. Overall, 75.5% of participants experienced ≥1 transition among 18,318 pairs of consecutive visits-4,174 of which were worsening and 2,606 were improving transitions. Adjusting for covariates, higher participation in each activity type was associated with lower odds of worsening (physical OR=0.71, 95% CI: 0.67-0.75; social OR=0.64, 95% CI: 0.58-0.70; and cognitive OR=0.79, 95% CI: 0.74-0.85), and higher odds of improving (physical OR=1.20, 95% CI: 1.11-1.28; social OR=1.45, 95% CI: 1.30-1.61; and cognitive OR=1.12, 95% CI: 1.03-1.22) in separate models. In combined models, physical and social activity remained associated with worsening and improving; cognitive activity was only associated with worsening. Physical, social, and cognitive activity engagement contributes to lower odds of worsening mobility disability and may promote recovery.

Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Mapping 15-year depressive symptom transitions in late life: population-based cohort study.

BACKGROUND: The longitudinal course of late-life depression remains under-studied. AIMS: To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns. METHOD: We analysed 15-year longitudinal data on 2745 dementia-free persons aged 60+ from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression (minor and major) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; subsyndromal depression (SSD) was operationalised as the presence of ≥2 symptoms without depression. Multistate survival models were used to map depression transitions, including death, and to examine the association of psychosocial (social network, connection and support), lifestyle (smoking, alcohol consumption and physical activity) and clinical (somatic disease count) factors with transition patterns. RESULTS: Over the follow-up, 19.1% had ≥1 transitions across depressive states, while 6.5% had ≥2. Each additional somatic disease was associated with a higher hazard of progression from no depression (No Dep) to SSD (hazard ratio 1.09; 1.07-1.10) and depression (Dep) (hazard ratio 1.06; 1.04-1.08), but also with a lower recovery (HRSSD-No Dep 0.95; 0.93-0.97 [where 'HR' refers to 'hazard ratio']; HRDep-No Dep 0.96; 0.93-0.99). Physical activity was associated with an increased hazard of recovery to no depression from SSD (hazard ratio 1.49; 1.28-1.73) and depression (hazard ratio 1.20; 1.00-1.44), while a richer social network was associated with both higher recovery from (HRSSD-No Dep 1.44; 1.26-1.66; HRDep-No Dep 1.51; 1.34-1.71) and lower progression hazards to a worse depressive state (HRNo Dep-SSD 0.81; 0.70-0.94; HRNo Dep-Dep 0.58; 0.46-0.73; HRSSD-Dep 0.66; 0.44-0.98). CONCLUSIONS: Older people may present with heterogeneous depressive trajectories. Targeting the accumulation of somatic diseases and enhancing social interactions may be appropriate for both depression prevention and burden reduction, while promoting physical activity may primarily benefit recovery from depressive disorders.

Early-life participation in cognitively stimulating activities and risk of depression and anxiety in late life.

BACKGROUND: Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life. METHODS: We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity. RESULTS: Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38-0.77) for late-life depression and an OR of 0.94 (95% CI 0.61-1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status. CONCLUSIONS: More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

Longitudinal association between depressive symptoms and cognitive function: the neurological mechanism of psychological and physical disturbances on memory.

BACKGROUND: The neural correlates underlying late-life depressive symptoms and cognitive deterioration are largely unclear, and little is known about the role of chronic physical conditions in such association. This research explores both concurrent and longitudinal associations between late-life depressive symptoms and cognitive functions, with examining the neural substrate and chronic vascular diseases (CVDs) in these associations. METHODS: A total of 4109 participants (mean age = 65.4, 63.0% females) were evaluated for cognitive functions through various neuropsychological assessments. Depressive symptoms were assessed by the Geriatric Depression Scale and CVDs were self-reported. T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) data were acquired in a subsample (n = 791). RESULTS: Cognitively, higher depressive symptoms were correlated with poor performance across all cognitive domains, with the strongest association with episodic memory (r = ‒0.138, p < 0.001). Regarding brain structure, depressive symptoms were negatively correlated with thalamic volume and white matter integrity. Further, white matter integrity was found to mediate the longitudinal association between depressive symptoms and episodic memory (indirect effect = -0.017, 95% CI -0.045 to -0.002) and this mediation was only significant for those with severe CVDs (ß = -0.177, p = 0.008). CONCLUSIONS: This study is one of the first to provide neural evidence elucidating the longitudinal associations between late-life depressive symptoms and cognitive dysfunction. Additionally, the severity of CVDs strengthened these associations, which enlightens the potential of managing CVDs as an intervention target for preventing depressive symptoms-related cognitive decline.

Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

BACKGROUND: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aß) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia. METHODS: A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aß42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis. RESULTS: Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (ß 0.11; 95% CI: 0.05-0.17). CONCLUSIONS: Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms.

Is Late-Onset Suicidal Behavior a Distinct Subtype?

This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

OBJECTIVES: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. DESIGN: Secondary cross-sectional analysis using latent profile analysis. SETTING: Multisite clinical trial in Toronto, Canada. PARTICIPANTS: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). MEASUREMENTS: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. RESULTS: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. CONCLUSION: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups.

Late Life Depression is Not Associated With Alzheimer-Type Tau: Preliminary Evidence From a Next-Generation Tau Ligand PET-MR Study.

OBJECTIVE: To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI). DESIGN: Monocentric, cross-sectional study. SETTING: University Psychiatric hospital, memory clinic and outpatient neurology practice. PARTICIPANTS: A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging. MEASUREMENTS: PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively. RESULTS: Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD. CONCLUSION: Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD.

The Role of State Versus Trait Anxiety on Cognition in Older Adults With Major Depressive Disorder.

OBJECTIVE: 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. DESIGN: Three-year longitudinal observational study of older adults with LLD who were offered antidepressant treatment. SETTING: Academic Health Center. METHODS: 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. RESULTS: 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. CONCLUSION: In LLD, individual increases in state and trait anxiety were associated with cognitive declines in different domains.

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.

Geroscience-Centric Perspective for Geriatric Psychiatry: Integrating Aging Biology With Geriatric Mental Health Research.

The geroscience hypothesis asserts that physiological aging is caused by a small number of biological pathways. Despite the explosion of geroscience research over the past couple of decades, the research on how serious mental illnesses (SMI) affects the biological aging processes is still in its infancy. In this review, we aim to provide a critical appraisal of the emerging literature focusing on how we measure biological aging systematically, and in the brain and how SMIs affect biological aging measures in older adults. We will also review recent developments in the field of cellular senescence and potential targets for interventions for SMIs in older adults, based on the geroscience hypothesis.

White Noise-Is Anxiety in Late-Life Associated With White Matter Hyperintensity Burden?

OBJECTIVE: We investigated the relationship between anxiety phenotypes (global anxiety, worry, and rumination) and white matter hyperintensities (WMH), with special consideration for the roles of age and executive function (EF). Our hypotheses were 1) anxiety phenotypes would be associated with WMH and 2) EF would moderate this relationship. DESIGN: Cross-sectional. SETTING: Participants were recruited from the local community (Pittsburgh, PA). PARTICIPANTS: We recruited 110 older adults (age ≥ 50) with varying worry severity and clinical comorbidity. INTERVENTIONS: Not applicable. MEASUREMENTS: Demographics (age, sex, race, education), clinical measures (cumulative illness burden, global anxiety, worry, and rumination), EF, and WMH quantified with magnetic resonance imaging. RESULTS: Lower global anxiety and worry severity were significantly correlated with higher WMH volume, though the global anxiety relationship was not significant after controlling for age. Rumination as not associated with WMH burden. EF was not correlated with either global anxiety, worry, rumination, or WMH. However, in those with advanced age and/or greater WMH burden, there was an association between worry and EF as well as EF and WMH. CONCLUSION: Longitudinal studies are needed in order to clarify the complex interactions between anxiety phenotypes, WMH, and EF.

Hoarding Symptoms in Late Life Depression are Associated With Greater Executive Dysfunction and Disability and Poorer Response to Depression Treatment.

OBJECTIVES: 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. DESIGN: Cross-sectional. SETTING: Outpatient psychiatry program. PARTICIPANTS: Eighty-three community-dwelling adults ages 65-90 with LLD. INTERVENTION: Problem-solving therapy. MEASUREMENTS: 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. RESULTS: 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, ß = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, ß = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, ß = -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, ß = 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, ß = -15.6, p = 0.035. CONCLUSIONS: 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.

Relationship of Hoarding and Depression Symptoms in Older Adults.

Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.

Improving Care for Late-Life Depression Through Partnerships With Community-Based Organizations: Results From the Care Partners Project.

OBJECTIVES: 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. DESIGN: Multisite, prepost evaluation. SETTING: Eight (n = 8) partnerships between primary care clinics and community-based organizations in California. PARTICIPANTS: 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. INTERVENTION: A CBO partner was added to augment CC for late-life depression in primary care. MEASUREMENTS: The PHQ-9 was used to identify depressed older adults and to monitor depression symptom severity during a course of care. RESULTS: 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. CONCLUSIONS: 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.

Differential Psychological Treatment Effects in Patients With Late-Life Depression and a History of Childhood Maltreatment.

OBJECTIVE: This is the first interventional study to assess the impact of childhood maltreatment (CM) on psychological treatment outcomes in patients with late-life depression (LLD). METHODS: This is a secondary analysis of a multicenter, randomized controlled trial with 251 participants aged ≥60 years with moderate to severe depression. Participants were randomly assigned to cognitive behavioral therapy for late life depression (LLD-CBT) or to a supportive intervention (SUI). Treatment outcomes were measured by changes in the Geriatric Depression Scale (GDS). RESULTS: In the intention-to-treat sample (n = 229), both LLD-CBT (n = 115) and SUI (n = 114) significantly reduced depressive symptoms in patients with CM, with large effects at post-treatment (d = 0.95 [95% CI: 0.65 to 1.25] in LLD-CBT; d = 0.82 [95% CI: 0.52 to 1.12] in SUI). A significant treatment group*CM interaction (F(1,201.31) = 4.71; p = .031) indicated greater depressive symptom reduction in LLD-CBT compared to SUI at week 5 and post-treatment for patients without CM, but not at 6-month follow-up. Across both treatments, higher severity of the CM subtype 'physical neglect' was associated with a smaller depressive symptom reduction (F(1,207.16) = 5.37; p = .021). CONCLUSIONS: Specific and non-specific psychotherapy effectively reduced depressive symptoms in older individuals with depression and early trauma. For patients without early trauma, LLD-CBT may be preferable over SUI. Considering early trauma subtypes may contribute to develop personalized treatment approaches.

Anxiety in late-life depression is associated with poorer performance across multiple cognitive domains.

OBJECTIVE: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains. METHOD: Older adults with major depressive disorder (N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning. RESULTS: Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity. CONCLUSIONS: Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

Age-related subtypes of late life depression and mortality: A prospective clinical cohort study.

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.

Characteristics of and Risk Factors for Depressive Symptoms Preceding Dementia: A Study of 82-Year-Old Men From the Uppsala Longitudinal Study of Adult Men.

BACKGROUND: Depression and dementia are known to be associated. The identification of characteristics distinguishing depression prodromal to dementia from other depressive symptoms would be of value for early identification of dementia. The study of risk factors for depressive symptoms prodromal to dementia could improve preventive care and provide clues to the causes of dementia. METHOD: Dementia-free 82-year-old participants were stratified into groups that did (n = 126) and did not (n = 378) subsequently develop dementia. Examinations took place from 2003 to 2005 and follow-up ended 1 January 2015. Their baseline characteristics and depressive symptoms, measured using the 15-item Geriatric Depression Scale (GDS-15), were compared. Multivariate regression analyses were performed for the two groups separately, with the total GDS-15 score as the dependent variable. RESULTS: The groups did not differ significantly in answers to any of the GDS-15 questions, or mean ± SD score, which was 2.4 ± 2.5 among those who developed dementia and 2.1 ± 2.3 among those who did not. (p = 0.33). Stroke before the age of 82 years and the inability to use stairs had significant impacts on the GDS-15 scores in both groups. For those who did not develop dementia, age, dependence in activities of daily living, and cancer also had significant impacts. Cancer had opposite associations with depressive symptoms in the two groups. CONCLUSIONS: No difference was found in depressive symptoms preceding and not preceding dementia using the GDS-15. The results suggest that risk factors for depressive symptoms may differ depending on whether they precede dementia.