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.

Feasibility, usability and clinical value of intensive longitudinal diary assessments in older persons with cognitive impairment and depressive symptoms.

OBJECTIVES: To evaluate the feasibility, usability and clinical value of daily diary assessments combined with actigraphy in older persons with cognitive impairment. METHODS: For 63 days, patients ≥60 years with cognitive impairments filled out a daily diary (including standardized questionnaires and cognitive test battery), and wore an actiwatch (sleep). After the study, participants and clinicians received personal feedback about patterns and daily triggers of depressive symptoms, sleep and cognitive performance. We assessed feasibility (participation rate, compliance and subjective burden), usability (variability and floor- or ceiling effects) and clinical value for patients and their clinicians (questionnaires). RESULTS: Of 96 eligible patients, 13 agreed to participate (13.5%). One patient dropped out after 2 days, another after 37 days, and another did not complete the cognitive test battery. Compliance rate was high (6.7-10% missing values). Subjective burden was relatively low. Time-series data showed sufficient variability and no floor- or ceiling effects, except for one relevant ceiling effect on the One Back task. The personal feedback report was considered insightful by 4 out of 11 participants and 5 out of 7 clinicians. CONCLUSION: Daily assessments are suitable for a minority of cognitively impaired older persons, but is helpful to increase insight into their symptoms.

Daily associations between affect and cognitive performance in older adults with depression and cognitive impairment: a series of seven single-subject studies in the Netherlands.

BACKGROUND: Comorbidity between depression and cognitive impairment is common in older adults, increases the disease burden disproportionally, and leads to diagnostic uncertainty. Insight into individual daily associations between affect and cognitive performance may help in personalizing diagnosis and treatment decisions. Our objective was to get insight into the daily associations between affect and cognitive performance within individual older adults. METHODS: In this single-subject study seven older adults with both depression and cognitive impairment filled in electronic diaries daily for 62-93 consecutive days evaluating positive affect (PA), negative affect (NA), working memory (WM) and visual learning (VL). Time-series analyses using vector autoregressive modelling, Granger causality tests and cumulative orthogonalized impulse response function analyses were performed for each individual separately. RESULTS: In one patient higher NA was associated with better WM the next day. For another patient days with higher NA and lower PA were days with worse WM. For a third patient better VL was associated with lower NA and higher PA the next day. No associations were found for four patients. CONCLUSIONS: These results highlight heterogeneity in the daily associations between affect and cognitive performance and stress the relevance of single-subject studies. These studies may be an important step towards personalized diagnosis and treatment in old age psychiatry.

Temporal dynamics of depression, cognitive performance and sleep in older persons with depressive symptoms and cognitive impairments: a series of eight single-subject studies.

OBJECTIVES: To investigate the presence, nature and direction of the daily temporal association between depressive symptoms, cognitive performance and sleep in older individuals. DESIGN, SETTING, PARTICIPANTS: Single-subject study design in eight older adults with cognitive impairments and depressive symptoms. MEASUREMENTS: For 63 consecutive days, depressive symptoms, working memory performance and night-time sleep duration were daily assessed with an electronic diary and actigraphy. The temporal associations of depressive symptoms, working memory and total sleep time were evaluated for each participant separately with time-series analysis (vector autoregressive modeling). RESULTS: For seven out of eight participants we found a temporal association between depressive symptoms and/or sleep and/or working memory performance. More depressive symptoms were preceded by longer sleep duration in one person (r = 0.39; p < .001), by longer or shorter sleep duration than usual in one other person (B = 0.49; p < .001), by worse working memory in one person (B = -0.45; p = .007), and by better working memory performance in one other person (B = 0.35; p = .009). Worse working memory performance was preceded by longer sleep duration (r = -.35; p = .005) in one person, by shorter or longer sleep duration in three other persons (B = -0.76; p = .005, B = -0.61; p < .001; B = -0.34; p = .002), and by more depressive symptoms in one person (B = -0.25; p = .009). CONCLUSION: The presence, nature and direction of the temporal associations between depressive symptoms, cognitive performance and sleep differed between individuals. Knowledge of personal temporal associations may be valuable for the development of personalized intervention strategies in order to maintain their health, quality of life, functional outcomes and independence.

Individual differences in the temporal relationship between sleep and agitation: a single-subject study in nursing home residents with dementia experiencing sleep disturbance and agitation.

OBJECTIVES: Previous studies on the interrelationship between sleep and agitation relied on group-aggregates and so results may not be applicable to individuals. This proof-of-concept study presents the single-subject study design with time series analysis as a method to evaluate the association between sleep and agitation in individual nursing home residents using actigraphy. METHOD: To record activity, three women and two men (aged 78-89 years) wore the MotionWatch 8© (MW8) for 9 consecutive weeks. Total sleep time and agitation were derived from the MW8 data. We performed time series analysis for each individual separately. To gain insight into the experiences with the actigraphy measurements, care staff filled out an investigator-developed questionnaire on their and participants' MW8 experiences. RESULTS: A statistically significant temporal association between sleep and agitation was present in three out of five participants. More agitation was followed by more sleep for participant 1, and by less sleep for participant 4. As for participants 3 and 4, more sleep was followed by more agitation. Two-thirds of the care staff members (16/24) were positive about the use of the MW8. Acceptability of the MW8 was mixed: two residents refused to wear the MW8 thus did not participate, one participant initially experienced the MW8 as somewhat unpleasant, while four participants seemed to experience no substantial problems. CONCLUSION: A single-subject approach with time series analysis can be a valuable tool to gain insight into the temporal relationship between sleep and agitation in individual nursing home residents with dementia experiencing sleep disturbance and agitation.

Intra-Individual Variability in Cognitive Performance Can Befuddle the Study of Cognitive Impairments and Decline.

Using group-aggregated results and snapshot assessments of cognitive performance may prove problematic if the assessed construct shows substantial and rapid variation over time. To illustrate the significance of this issue, we analyzed cognitive performance data of ten older adults undergoing daily computerized cognitive assessments (CogState Brief Battery) for 36-93 days. In all cases, the day-to-day intra-individual variability was substantial when compared with group-level, between-person variability. This indicates that the results of studies using single snapshot assessments of cognitive functioning should be interpreted with caution. Additionally, group-aggregated measures of cognitive performance may not directly extrapolate to an individual.

Subtypes of Late-Life Depression: A Data-Driven Approach on Cognitive Domains and Physical Frailty.

BACKGROUND: With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty. METHODS: A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty. RESULTS: A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression ("mild" and "severe" depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as "amnestic depression," "frail-depressed, physically dominated," and "frail-depressed, cognitively dominated." The prospective analyses showed that patients in the subgroup of "mild depression" and "amnestic depression" had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates. CONCLUSIONS: Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation.

Single-Subject Research in Psychiatry: Facts and Fictions.

Scientific evidence in the field of psychiatry is mainly derived from group-based ("nomothetic") studies that yield group-aggregated results, while often the need is to answer questions that apply to individuals. Particularly in the presence of great inter-individual differences and temporal complexities, information at the individual-person level may be valuable for personalized treatment decisions, individual predictions and diagnostics. The single-subject study design can be used to make inferences about individual persons. Yet, the single-subject study is not often used in the field of psychiatry. We believe that this is because of a lack of awareness of its value rather than a lack of usefulness or feasibility. In the present paper, we aimed to resolve some common misconceptions and beliefs about single-subject studies by discussing some commonly heard "facts and fictions." We also discuss some situations in which the single-subject study is more or less appropriate, and the potential of combining single-subject and group-based study designs into one study. While not intending to plea for single-subject studies at the expense of group-based studies, we hope to increase awareness of the value of single-subject research by informing the reader about several aspects of this design, resolving misunderstanding, and providing references for further reading.

ACTman: Automated preprocessing and analysis of actigraphy data.

OBJECTIVES: To introduce a novel software-library called Actigraphy Manager (ACTman) which automates labor-intensive actigraphy data preprocessing and analyses steps while improving transparency, reproducibility, and scalability over software suites traditionally used in actigraphy research practice. DESIGN: Descriptive. METHODS: Use cases are described for performing a common actigraphy task in ACTman and alternative actigraphy software. Important inefficiencies in actigraphy workflow are identified and their consequences are described. We explain how these hinder the feasibility of conducting studies with large groups of athletes and/or longer data collection periods. Thereafter, the information flow through the ACTman software is described and we explain how it alleviates aforementioned inefficiencies. Furthermore, transparency, reproducibility, and scalability issues of commonly used actigraphy software packages are discussed and compared with the ACTman package. RESULTS: It is shown that from an end-user perspective ACTman offers a compact workflow as it automates many preprocessing and analysis steps that otherwise have to be performed manually. When considering transparency, reproducibility, and scalability the design of the ACTman software is found to outperform proprietary and open-source actigraphy software suites. As such, ACTman alleviates important bottlenecks within actigraphy research practice. CONCLUSIONS: ACTman facilitates the current transition towards larger datasets containing data of multiple athletes by automating labor-intensive preprocessing and analyses steps within actigraphy research. Furthermore, ACTman offers many features which enhance user-convenience and analysis customization, such as moving window functionality and period selection options. ACTman is open-source and thus fully verifiable, in contrast with many proprietary software packages which remain a black box for researchers.

A longitudinal study of the impact of social network size and loneliness on cognitive performance in depressed older adults.

Objectives: To examine the association of social network size and loneliness with cognitive performance and -decline in depressed older adults.Method: A sample of 378 older adults [70.7 (7.4) years] with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of current depressive disorder were recruited from primary care and specialized mental health care. Cognitive performance was assessed at baseline and 2 years follow-up with the Stroop colored-word test, a modified version of the Auditory Verbal Learning Task and the Digit Span subtest from the Wechsler Adult Intelligence Scale, encompassing four cognitive domains; processing speed, interference control, memory, and working memory. Social network size was assessed with the Close Person Inventory and loneliness with the de Jong Gierveld Loneliness Scale at baseline.Results: After adjusting for baseline working memory performance, loneliness was associated with impaired working memory after 2 years [B = -0.08 (-0.17 to 0.00)]. This association was no longer significant after adjusting for age, sex, education level, physical activity, alcohol use and depressive symptom severity [B = -0.07 (-0.16 to 0.03)]. A backward elimination procedure revealed education level to be the only covariable to explain this association. Loneliness was not associated with impairments or decline in other cognitive domains. Social network size was not associated with cognitive impairments or decline.Conclusion: Social network size and loneliness do not predict cognitive decline in depressed older adults.

Sertraline and Mirtazapine Versus Placebo in Subgroups of Depression in Dementia: Findings From the HTA-SADD Randomized Controlled Trial.

OBJECTIVE: Studies have shown that antidepressants are no better than placebo in treating depression in dementia. The authors examined antidepressant efficacy in subgroups of depression in dementia with different depressive symptom profiles. METHODS: This study focuses on exploratory secondary analyses on the randomized, parallel-group, double-blind, placebo-controlled Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial. The setting included old-age psychiatry services in nine centers in England. The participants included 326 patients meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association probable/possible Alzheimer disease criteria, and Cornell Scale for Depression in Dementia (CSDD) scores of 8 or more. Intervention was placebo (n = 111), sertraline (n = 107), or mirtazapine (n = 108). Latent class analyses (LCA) on baseline CSDD items clustered participants into symptom-based subgroups. Mixed-model analysis evaluated CSDD improvement at 13 and 39 weeks by randomization in each subgroup. RESULTS: LCA yielded 4 subgroups: severe (n = 34), psychological (n = 86), affective (n = 129), and somatic (n = 77). Mirtazapine, but not sertraline, outperformed placebo in the psychological subgroup at week 13 (adjusted estimate: -2.77 [standard error (SE) 1.16; 95% confidence interval: -5.09 to -0.46]), which remained, but lost statistical significance at week 39 (adjusted estimate: -2.97 [SE 1.59; 95% confidence interval: -6.15 to 0.20]). Neither sertraline nor mirtazapine outperformed placebo in the other subgroups. CONCLUSION: Because of the exploratory nature of the analyses and the small sample sizes for subgroup analysis there is the need for caution in interpreting these data. Replication of the potential effects of mirtazapine in the subgroup of those with depression in dementia with "psychological" symptoms would be valuable. These data should not change clinical practice, but future trials should consider stratifying types of depression in dementia in secondary analyses.

A bi-factor model of the Montgomery Åsberg depression rating scale and future cognitive impairments in older adults: A 6-year follow-up study.

Depression has been found to be associated with cognitive decline. This study evaluated the association of general depressive symptoms and motivational-related symptoms with cognitive impairment 6 years later and to explore the role of potential underlying mechanisms. In 2690 cognitively healthy persons aged ≥60 from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) depressive symptoms were derived from the Montgomery Åsberg Depression Rating Scale (MADRS). Cognitive performance was assessed at baseline and 6 years later in 1810 persons with the Mini Mental State Examination (global cognition), Digit Span Forward (short-term memory), Digit Span Backward (working memory), Clock-test (visuospatial construction), and the 5-item test (immediate and delayed recall). Bi-factor analysis on the MADRS yielded a General Depression factor and an unrelated Motivational factor. After adjusting for demographics, the General Depression factor was only associated with 6-year impairment in delayed recall (OR (95% CI): 1.18 (1.04-1.34)). This association was no longer significant after adjusting for demographics, cardiovascular risk, lifestyle factors and medication use. The Motivational factor was not significantly associated with future cognitive impairments after adjusting for demographics. Concluding, almost all associations of general depressive symptoms and motivational-related symptoms with future cognitive impairments appeared to be confounded by demographics. Only the association of general depressive symptoms with future memory impairments appeared to be explained by a combination of demographics, cardiovascular risk, lifestyle and medication use.

The relationship between depression and executive function and the impact of vascular disease burden in younger and older adults.

Background: depression is associated with worse executive function, but underlying mechanisms might differ by age. Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age. Method: among 83,613 participants of Lifelines (population-based cohort study), linear regression analyses were applied to examine the association between executive function (Ruff Figural Fluency test, dependent variable) and depression according to DSM-IV criteria (Mini International Neuropsychiatric Interview, independent variable). Results: adjusted for demographic characteristics, major depressive disorder was associated with a lower level of executive function in both younger and older adults. Minor depressive disorder was only associated with worse executive function in younger adults. Adding vascular disease burden to the final model with major depressive disorder, reduced this strength of this association by 5.9% in younger and 5.0% in older adults. Conclusions: major depression was associated with worse executive function across the lifespan, but minor depression only in younger adults. The impact of vascular burden on the association did not differ between younger and older adults. Therefore, vascular risk reduction is important in both age groups.

The Prognostic Effect of Physical Health Complaints With New Cardiac Events and Mortality in Patients With a Myocardial Infarction.

BACKGROUND: Self-rated general health has been associated with worse outcome after a myocardial infarction (MI). Previously, however, concurrent depression or anxiety was not taken into account. OBJECTIVE: To evaluate the effect of physical health complaints post-MI on cardiac prognosis adjusting for cardiac disease severity, depression, and anxiety. METHODS: The somatic subscale of the Health Complaints Scale was administered to 424 patients with MI at 3 and 12 months post-MI. Types and trajectories of health complaints were identified with latent transition analysis. The prognostic effect of Health Complaints Scale sum-score at 3 months, and of types and trajectories of health complaints on combined end points (new cardiac events and mortality) was evaluated with Cox regression. Adjustments were made for age, sex, education level, living alone, history of MI, left ventricular ejection fraction, depressive symptoms, and generalized anxiety disorder. RESULTS: Overall, 189 (44.9%) patients with MI had a cardiac event or died during a mean follow-up of 5.7 (3.1) years. In the fully adjusted model, Health Complaints Scale sum-score predicted outcome (hazard ratio [HR] = 1.02 [95% CI: 1.00-1.05]). Latent transition analysis distinguished 5 groups at 3 and 12 months characterized by (1) no/minimal complaints, (2) cardiac complaints, (3) lack of energy, (4) sleep problems, and (5) mixed health complaints, resulting in 25 transition classes. Patients with cardiac and energy complaints at 3 months (HRcardiac = 1.55 [1.15-2.10] and HRenergy = 1.35[1.00-1.81]) and those with new or persistent cardiac, energy, and mixed complaints over time had a worse prognosis (HRcardiac = 1.55 [1.11-2.16], HRmixed = 1.71 [1.19-2.47], and HRenergy = 1.51 [1.09-2.08]). CONCLUSIONS: Physical health complaints are predictors of cardiac outcome independent from cardiac disease, depression, and anxiety. Type and trajectories of health complaints may have additional prognostic significance.

The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study.

OBJECTIVE: Poor social functioning is associated with cognitive decline in older adults. It is unclear whether social functioning is also associated with subjective memory complaints (SMC). We investigated the association between social functioning and incident SMC and SMC recovery. METHODS: A population-based sample of 8762 older adults (aged ≥65 years) with good objective cognitive functioning at baseline (MMSE ≥26) from the LifeLines Cohort Study were followed for 1.5 years. Self-reported SMC were measured at baseline and after 1.5 years follow-up. Aspects of social functioning included marital status, household composition, social network size, social activity, quality of social relationships, social support, affection, behavioral confirmation, and status. RESULTS: Thirteen percent (513/3963) developed SMC during follow-up (incident SMC). Multivariate logistic regression analyses (adjusted for age, gender, education level, physical activity, alcohol use, smoking status, depression, arrhythmia, myocardial infarction, heart failure, stroke) showed that participants with better feelings of affection, behavioral confirmation and stable good social support had a lower risk of incident SMC. Thirty-four percent (1632/4799) reported recovery. Participants with good social functioning at baseline on all determinants reported more SMC recovery. People who remained stable in a relationship, stable in good quality of social relationships or increased in quality of social relationships more often report SMC recovery. CONCLUSIONS: Good social functioning is associated with less incident SMC and more SMC recovery over a follow-up period of 1.5 years. Albeit future confirmative studies are needed, we argue for targeting also social functioning when designing multidomain interventions to prevent or slow down cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.

The influence of thoughts of death and suicidal ideation on the course of depression in older depressed patients.

OBJECTIVE: Thoughts of death are not regularly included in diagnostic instruments and rarely examined separately from thoughts of suicide. This exploratory study examined whether thoughts of death and thoughts of suicide affect the course of late-life depressive disorders. METHODS: In 378 depressed older persons, thoughts of death and thoughts of suicide were assessed using questions from the Composite International Diagnostic Interview. After 2 years, the presence of a DSM-IV-TR diagnosis of minor or major depression or dysthymia was assessed with the Composite International Diagnostic Interview. The Inventory of Depressive Symptomatology was administered every 6 months up till 3-year follow-up. RESULTS: Multinomial logistic regression showed that thoughts of death as well as thoughts of suicide predicted double depression at follow-up (OR = 2.14 [95% CI: 1.04-4.40] and OR = 6.47 [95% CI: 2.22-3.02], respectively), compared with patients without these thoughts. Results became non-significant when adjusted for baseline depression severity (OR = 1.17 [95% CI: 0.52-2.63] and OR = 2.57 [95% CI: 0.79-8.84], respectively). Mixed linear models showed that severity of depression was lowest in the reference group, while symptoms decreased more over time in those with either thoughts of death or suicide. CONCLUSIONS: Patients with thoughts of death or with thoughts of suicide were more severely depressed at baseline and follow-up, with the highest risk of being depressed at follow-up for patients with thoughts of suicide. These associations could be explained by baseline depression severity. The results suggest that thoughts of death and thoughts of suicide are important risk markers in predicting the course of depression. Copyright © 2016 John Wiley & Sons, Ltd.

Prognostic association of cardiac anxiety with new cardiac events and mortality following myocardial infarction.

BACKGROUND: General anxiety and depressive symptoms following a myocardial infarction are associated with a worse cardiac prognosis. However, the contribution of specific aspects of anxiety within this context remains unclear. AIMS: To evaluate the independent prognostic association of cardiac anxiety with cardiac outcome after myocardial infarction. METHOD: We administered the Cardiac Anxiety Questionnaire (CAQ) during hospital admission (baseline, n = 193) and 4 months (n = 147/193) after discharge. CAQ subscale scores reflect fear, attention, avoidance and safety-seeking behaviour. Study end-point was a major adverse cardiac event (MACE): readmission for ischemic cardiac disease or all-cause mortality. In Cox regression analysis, we adjusted for age, cardiac disease severity and depressive symptoms. RESULTS: The CAQ sum score at baseline and at 4 months significantly predicted a MACE (HRbaseline = 1.59, 95% CI 1.04-2.43; HR4-months = 1.77, 95% CI 1.04-3.02) with a mean follow-up of 4.2 (s.d. = 2.0) years and 4.3 (s.d. = 1.7) years respectively. Analyses of subscale scores revealed that this effect was particularly driven by avoidance (HRbaseline = 1.23, 95% CI 0.99-1.53; HR4-months = 1.77, 95% CI 1.04-1.83). CONCLUSIONS: Cardiac anxiety, particularly anxiety-related avoidance of exercise, is an important prognostic factor for a MACE in patients after myocardial infarction, independent of cardiac disease severity and depressive symptoms.

Neighborhood income and major depressive disorder in a large Dutch population: results from the LifeLines Cohort study.

BACKGROUND: Previous studies are inconclusive on whether poor socioeconomic conditions in the neighborhood are associated with major depressive disorder. Furthermore, conceptual models that relate neighborhood conditions to depressive disorder have not been evaluated using empirical data. In this study, we investigated whether neighborhood income is associated with major depressive episodes. We evaluated three conceptual models. Conceptual model 1: The association between neighborhood income and major depressive episodes is explained by diseases, lifestyle factors, stress and social participation. Conceptual model 2: A low individual income relative to the mean income in the neighborhood is associated with major depressive episodes. Conceptual model 3: A high income of the neighborhood buffers the effect of a low individual income on major depressive disorder. METHODS: We used adult baseline data from the LifeLines Cohort Study (N = 71,058) linked with data on the participants' neighborhoods from Statistics Netherlands. The current presence of a major depressive episode was assessed using the MINI neuropsychiatric interview. The association between neighborhood income and major depressive episodes was assessed using a mixed effect logistic regression model adjusted for age, sex, marital status, education and individual (equalized) income. This regression model was sequentially adjusted for lifestyle factors, chronic diseases, stress, and social participation to evaluate conceptual model 1. To evaluate conceptual models 2 and 3, an interaction term for neighborhood income*individual income was included. RESULTS: Multivariate regression analysis showed that a low neighborhood income is associated with major depressive episodes (OR (95 % CI): 0.82 (0.73;0.93)). Adjustment for diseases, lifestyle factors, stress, and social participation attenuated this association (ORs (95 % CI): 0.90 (0.79;1.01)). Low individual income was also associated with major depressive episodes (OR (95 % CI): 0.72 (0.68;0.76)). The interaction of individual income*neighborhood income on major depressive episodes was not significant (p = 0.173). CONCLUSIONS: Living in a low-income neighborhood is associated with major depressive episodes. Our results suggest that this association is partly explained by chronic diseases, lifestyle factors, stress and poor social participation, and thereby partly confirm conceptual model 1. Our results do not support conceptual model 2 and 3.

Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies.

BACKGROUND: Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. METHODS: MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. RESULTS: We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. CONCLUSIONS: Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies.