Depression and chronic diseases in old age : understanding their interplay for better health

Late-life depression is intricately linked with somatic diseases. This thesis aimed to systematically explore this complex interplay. Specifically, we investigated: 1) the symptom-level interconnectedness between depression and somatic diseases, 2) the association of depression with somatic multimorbidity accumulation, 3) the role of somatic disease burden in depression development, and 4) the association of somatic burden with transitions across depressive states in older adults. Data were gathered from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a populationbased study comprising 3,363 individuals aged 60+ years who underwent clinical assessments over a 15-year follow-up. Study I. Using a network approach, we aimed to describe the interconnectedness between depressive symptoms and somatic disease burden in older people. We found that sadness, pessimism, anxiety, and suicidal thoughts were central to the network, whereas somatic symptoms of depression appeared peripherally with fewer interconnections. When examining the association between depressive symptoms and measures of somatic disease burden, we found that suicidal thoughts, reduced appetite, and cognitive difficulties were bridge symptoms, linking late-life depression with somatic health. Study II. We investigated the impact of depression severity and phenotypes (i.e., affective, anxiety, cognitive, and psychomotor) on the progression of somatic multimorbidity over 15 years. Compared to those without depression, individuals with major (β*year: 0.33, 95%CI: 0.06-0.61) and subsyndromal depression (β*year: 0.21, 95%CI: 0.12-0.30) presented an accelerated accumulation of somatic multimorbidity. An increase in the cognitive phenotype burden (and not in the other three) was associated with faster accumulation of somatic diseases in old age (β*year: 0.07, 95%CI: 0.03-0.10). Study III. We aimed to examine the association between quantitative and qualitative measures of somatic disease burden and the incidence of depression in older adults. Each additional somatic disease was associated with an increased hazard of depression over a 15-year follow-up (HR 1.16, 95%CI: 1.08-1.24). Individuals presenting with disease patterns of sensory/anemia (HR 1.91, 95%CI: 1.03-3.53), thyroid/musculoskeletal (HR 1.90, 95%CI: 1.06-3.39), and cardiometabolic patterns (HR 2.77, 95%CI: 1.40-5.46) had higher depression hazards compared to those without multimorbidity. In the subsample of multimorbid participants, the cardiometabolic pattern remained associated with a higher depression risk (HR 1.71, 95%CI: 1.02-2.84) compared to the unspecific pattern. Study IV. We examined the course of old-age depression by investigating 15-year transitions along the depressive continuum and exploring time-varying factors associated with specific transition patterns. Over the follow-up, 19.1% had ≥1 transitions across depressive states (no depression, subsyndromal depression [SSD], depression), while 6.5% had ≥2 transitions. A higher number of somatic diseases was associated with progression from no depression to both SSD (HR 1.09, 95%CI: 1.07-1.10) and depression (HR 1.06, 95%CI: 1.04-1.08), and with lower recovery rates from SSD (HR 0.95, 95%CI: 0.93- 0.97) and depression (HR 0.96, 95%CI: 0.93-0.99). A richer social network was linked to lower transition rates to depressive states (HRNoDep-SSD 0.81, 95%CI: 0.70-0.94; HRNoDep-Dep 0.58, 95%CI: 0.46-0.73; HRSSD-Dep 0.66, 95%CI: 0.44-0.98), and higher recovery rates (HRSSD-NoDep 1.44, 95%CI: 1.26-1.66; HRDep-NoDep 1.51, 95%CI: 1.34-1.71). Being physically active was associated with higher recovery rates (HRSSD-NoDep 1.49, 95%CI: 1.28-1.73; HRDep-NoDep 1.20, 95%CI: 1.00-1.44). Conclusions. Our findings suggest that several dimensions of complexity characterize the interconnection of depression and somatic disease burden in old age. A symptomlevel characterisation of depression, along with a consideration of subsyndromal severity, may help clarify the comorbidity of depression and somatic diseases, as well as predict health decline in people with depressive symptoms. Similarly, recognizing disease patterns may help improve risk stratification for depression development in clinically complex older adults. Last, the natural course of depression in late life is dynamic and involves complex patterns of transitions through symptom severities, which can be influenced by the time-varying burden of somatic diseases. Developing person-centered care that integrates these complexities could enhance resilience and contribute to better health in old age

Risk Prediction Models for Depression in Community-Dwelling Older Adults

Objective: To develop streamlined Risk Prediction Models (Manto RPMs) for late-life depression. Design: Prospective study. Setting: The Survey of Health, Ageing and Retirement in Europe (SHARE) study. Participants: Participants were community residing adults aged 55 years or older. Measurements: The outcome was presence of depression at a 2-year follow up evaluation. Risk fac-tors were identified after a literature review of longitudinal studies. Separate RPMs were developed in the 29,116 participants who were not depressed at baseline and in the combined sample of 39,439 of non-depressed and depressed subjects. Models derived from the combined sample were used to develop a web-based risk calculator. Results: The authors identified 129 predictors of late-life depression after reviewing 227 studies. In non-depressed participants at baseline, the RPMs based on regression and Least Absolute Shrinkage and Selection Operator (LASSO) penalty (34 and 58 predictors, respectively) and the RPM based on Artificial Neural Networks (124 predictors) had a similar perfor-mance (AUC: 0.730-0.743). In the combined depressed and non-depressed par-ticipants at baseline, the RPM based on neural networks (35 predictors; AUC: 0.807; 95% CI: 0.80-0.82) and the model based on linear regression and LASSO penalty (32 predictors; AUC: 0.81; 95% CI: 0.79-0.82) had satisfactory accu-racy. Conclusions: The Manto RPMs can identify community-dwelling older individuals at risk for developing depression over 2 years. A web-based calcula-tor based on the streamlined Manto model is freely available at https://manto. unife.it/for use by individuals, clinicians, and policy makers and may be used to target prevention interventions at the individual and the population levels

Measuring gait speed to better identify prodromal dementia

Abstract Slow gait speed has been shown to predict incident dementia and cognitive decline in older individuals. We aimed to summarize the evidence concerning the association of slow gait speed with cognitive decline and dementia, and discuss the possible shared pathways leading to cognitive and motor impairments, under the unifying hypothesis that body and mind are intimately connected. This is a scoping review supported by a systematic search of the literature, performed on PubMed and Web of Science. Longitudinal studies providing information on the role of gait speed in the prediction of cognitive decline and dementia in cognitively intact people and in those with initial cognitive impairment were eligible. Of 39 studies selected, including overall 57,456 participants, 33 reported a significant association between gait speed and cognitive outcomes, including dementia. Neurodegenerative pathology and cerebrovascular burden may damage cerebral areas involved in both cognitive functions and motor control. At the same time, systemic conditions, characterized by higher cardiorespiratory, and metabolic and inflammatory burden, can affect a number of organs and systems involved in motor functions, including the brain, having ultimately an impact on cognition. The interplay of body and mind seems relevant during the development of cognitive decline and dementia. The measurement of gait speed may improve the detection of prodromal dementia and cognitive impairment in individuals with and without initial cognitive deficits. The potential applicability of such a measure in both clinical and research settings points at the importance of expanding our knowledge about the common underlying mechanisms of cognitive and motor decline

social engagement in late life may attenuate the burden of depressive symptoms due to financial strain in childhood

Abstract Background : It remains poorly understood if childhood financial strain is associated with old-age depression and if active social life may mitigate this relationship. Aims : To investigate the association between childhood financial strain and depressive symptoms during aging; to examine whether late-life social engagement modifies this association. Method : 2884 dementia-free individuals (aged 60+) from the Swedish National study of Aging and Care-Kungsholmen were clinically examined over a 15-year follow-up. Presence of childhood financial strain was ascertained at baseline. Depressive symptoms were repeatedly assessed with the Montgomery–Asberg Depression Rating Scale. Social engagement comprised information on baseline social network and leisure activities. Linear, logistic and mixed-effect models estimated baseline and longitudinal associations accounting for sociodemographic, clinical, and lifestyle factors. Results : Childhood financial strain was independently associated with a higher baseline level of depressive symptoms (β = 0.37, 95%CI 0.10-0.65), but not with symptom change over time. Relative to those without financial strain and with active social engagement, depressive burden was increased in those without financial strain but with inactive social engagement (β = 0.43, 95%CI: 0.15-0.71), and in those with both financial strain and inactive engagement (β = 0.99; 95%CI: 0.59-1.40). Individuals with financial strain and active social engagement exhibited similar depressive burden as those without financial strain and with active social engagement. Limitations : Recall bias and reverse causality may affect study results, although sensitivity analyses suggest their limited effect. Conclusions : Early-life financial strain may be of lasting importance for old-age depressive symptoms. Active social engagement in late-life may mitigate this association

Sleep disturbances and the speed of multimorbidity development in old age : results from a longitudinal population-based study

Sleep disturbances are prevalent among older adults and are associated with various individual diseases. The aim of this study was to investigate whether sleep disturbances are associated with the speed of multimorbidity development among older adults. Data were gathered from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study of subjects aged 60+ (N = 3363). The study included a subsample (n = 1189) without multimorbidity at baseline (< 2 chronic diseases). Baseline sleep disturbances were derived from the Comprehensive Psychiatric Rating Scale and categorized as none, mild, and moderate-severe. The number of chronic conditions throughout the 9-year follow-up was obtained from clinical examinations. Linear mixed models were used to study the association between sleep disturbances and the speed of chronic disease accumulation, adjusting for sex, age, education, physical activity, smoking, alcohol consumption, depression, pain, and psychotropic drug use. We repeated the analyses including only cardiovascular, neuropsychiatric, or musculoskeletal diseases as the outcome. Moderate-severe sleep disturbances were associated with a higher speed of chronic disease accumulation (ß /year = 0.142, p = 0.008), regardless of potential confounders. Significant positive associations were also found between moderate-severe sleep disturbances and neuropsychiatric (ß /year = 0.041, p = 0.016) and musculoskeletal (ß /year = 0.038, p = 0.025) disease accumulation, but not with cardiovascular diseases. Results remained stable when participants with baseline dementia, cognitive impairment, or depression were excluded. The finding that sleep disturbances are associated with faster chronic disease accumulation points towards the importance of early detection and treatment of sleep disturbances as a possible strategy to reduce chronic multimorbidity among older adults. The online version contains supplementary material available at 10.1186/s12916-020-01846-w

Neuroactive Steroids in First-Episode Psychosis: A Role for Progesterone?

Neuroactive steroids may play a role in the pathophysiology of psychotic disorders, but few studies examined this issue. We compared serumlevels of cortisol, testosterone, dehydroepiandrosterone, and progesterone between a representative sample of firstepisode psychosis (FEP) patients and age- and gender-matched healthy subjects. Furthermore, we analyzed the associations between neuroactive steroids levels and the severity of psychotic symptom dimensions.Male patients had lower levels of progesterone than controls

The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition

Background: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression.Methods: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions.Results: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations.Discussion: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence

Background The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. Methods A cross-sectional study including 3283 adolescents 15-16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. Results Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5-2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. Conclusions Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments

Choroidal Neovascularization in a Patient with Crohn's Disease

Purpose: To report a case of subfoveal choroidal neovascularization (CNV) in a patient with Crohn's disease (CD) and to discuss a possible association between these two conditions. Methods: This is an observational case report. Results: A 69-year-old male affected by CD was referred to our department because of sudden visual acuity drop in the left eye. A subfoveal CNV was diagnosed based on slit-lamp fundus biomicroscopy and fluorescein angiography. Color fundus photography, infrared autofluorescence and spectral-domain optical coherence tomography imaging of both eyes were also performed. Following six intravitreal ranibizumab injections, visual improvement was obtained with no related adverse events. Conclusion: We report a case of CNV as a possible rare extraintestinal manifestation of CD. The use of ranibizumab successfully impacted on CNV, while not affecting CD, which remained quiescent

Optic Nerve Head and Macular Choroidal Vascularization in Patients Affected by Normal Tension Glaucoma and Non-Arteritic Ischemic Optic Neuropathy

"Two consecutive series of patients affected by chronic optic neuropathy due to NTG and N-AION, as well as a cohort of healthy subjects, underwent complete ophthalmological examination, Humphrey Visual Field (HVF), Enhanced Depth Imaging Optical Coherence Tomography (EDI OCT). Peripapillary choroidal thickness has been measured on peripapillary circular scans at 3, 6, 9, 12 clocks' hours. Macular choroidal thickness was evaluated on line scans below the subfoveal region (SF), and at 750- and 1000-μm intervals, nasally, inferiorly, temporally and superiorly to the fovea. Ganglion Cell Complex (GCC) thickness was also considered in the study. T-test and ANOVA were used to perform statistical analysis.