Profiling patients on a proposed ‘immunometabolic depression’ (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.

Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001–0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01–0.22, I2 = 23.91%), with a higher – but still small – effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.

Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.

High cognitive activity possibly reduces the risk of cognitive decline and dementia.

To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.

Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.

Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.

A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Depression is a global mental health challenge. We assessed the prevalence of depressive symptoms and their association with age, chronic conditions, and health status among middle-aged and elderly people in peri-urban Dar es Salaam, Tanzania.

Depressive symptoms were measured in 2,220 adults aged over 40 years from two wards of Dar es Salaam using the ten-item version of the Center of Epidemiologic Studies Depression Scale (CES-D-10) and a cut-off score of 10 or higher. The associations of depressive symptoms with age, 13 common chronic conditions, multimorbidity, self-rated health and any limitation in six activities of daily living were examined in univariable and multivariable logistic regressions.

The estimated prevalence of depressive symptoms was 30.7% (95% CI 28.5–32.9). In univariable regressions, belonging to age groups 45–49 years (OR 1.35 [95% CI 1.04–1.75]) and over 70 years (OR 2.35 [95% CI 1.66–3.33]), chronic conditions, including ischemic heart disease (OR 3.43 [95% CI 2.64–4.46]), tuberculosis (OR 2.42 [95% CI 1.64–3.57]), signs of cognitive problems (OR 1.90 [95% CI 1.35–2.67]), stroke (OR 1.56 [95% CI 1.05–2.32]) and anemia (OR 1.32 [95% CI 1.01–1.71]) and limitations in activities of daily living (OR 1.35 [95% CI 1.07–1.70]) increased the odds of depressive symptoms. Reporting good or very good health was associated with lower odds of depressive symptoms (OR 0.48 [95% CI 0.35–0.66]). Ischemic heart disease and tuberculosis remained independent predictors of depressive symptoms in multivariable regressions.

Depressive symptoms affected almost one in three people aged over 40 years. Their prevalence differed across age groups and was moderated by chronic conditions, health status and socioeconomic factors.

Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors.

We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the ‘LIfestyle for BRAin health’ (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score.

During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)].

Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist.

With the projected surge in global dementia cases and no curative treatment available, research is increasingly focusing on lifestyle factors as preventive measures. Social and cognitive leisure activities are promising targets, but it is unclear which types of activities are more beneficial. This study investigated the individual and joint contribution of cognitive and social leisure activities to dementia risk and whether they modify the risks associated with other potentially modifiable and non-modifiable risk factors.

We used data from the English Longitudinal Study of Ageing (ELSA) from 7917 participants, followed up from 2008/2009 (Wave 4) until 2018/2019 (Wave 9) for incident dementia. Self-reported baseline cognitive activities (e.g. ‘reading the newspaper’), the number of social memberships (e.g. being a member of a social club) and social participation (e.g. ‘going to the cinema’) were clustered into high and low based on a median split. Subsequently, their individual and joint contribution to dementia risk, as well as their interaction with other dementia risk factors, were assessed with Cox regression models, adjusting for age, sex, level of education, wealth and a composite score of 11 lifestyle-related dementia risk factors.

After a median follow-up period of 9.8 years, the dementia incidence rate was 54.5 cases per 10.000 person-years (95% CI 49.0–60.8). Adjusting for demographic and other lifestyle-related risk factors, higher engagement in cognitive activities (HR = 0.58; 95% CI 0.40–0.84), a greater number of social memberships (HR = 0.65; 95% CI 0.51–0.84) and more social participation (HR = 0.71; 95% CI 0.54–0.95) were associated with lower dementia risk. In a joint model, only engagement in cognitive activities (HR = 0.60; 95% CI 0.40–0.91) and social memberships (HR = 0.75; 95% CI 0.56–0.99) independently explained dementia risk. We did not find any interaction with other modifiable and non-modifiable risk factors.

Engagement in cognitive and social leisure activities may be beneficial for overall dementia risk, independent of each other and other risk factors. Both types of activities may be potential targets for dementia prevention measures and health advice initiatives.

Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals.

We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time.

The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity.

We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.

To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD.

The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included.

Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of ‘positive’ nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%.

Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of ‘positive’ results and selective reporting of outcomes are possible mechanisms.

Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).

Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.

An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.

Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.