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

The role of extracerebral cholesterol homeostasis and ApoE e4 in cognitive decline

AbstractWe examined the associations between extracerebral markers of cholesterol homeostasis and cognitive decline over 6 years of follow-up, and studied the modifying effect of apolipoprotein E (ApoE) e4. Data were collected in the Longitudinal Aging Study Amsterdam (n = 967, with longitudinal data on cognition, ages ≥ 65 years) and analyzed using linear mixed models. General cognition (Mini-Mental State Examination; MMSE), memory (Auditory Verbal Learning Test), and information processing speed (Coding task) were measured. The results show that ApoE e4 was a significant effect modifier. Significant associations were found only in ApoE e4 noncarriers (n = 718). We found a nonlinear negative association between the ratio of lanosterol to cholesterol (≤ 189.96 ng/mg), a marker for cholesterol synthesis, and general cognition. Lower cholesterol absorption, i.e., lower ratios of campesterol and sitosterol to cholesterol, as well as a higher rate of cholesterol synthesis relative to absorption were associated with lower information processing speed. In ApoE e4 carriers, the negative association between the ratio of campesterol to cholesterol and memory reached borderline significance. Future research should focus on the interaction between (disturbed) cholesterol homeostasis and ApoE e4 status with respect to dementia

Determinants and consequences of polypharmacy in patients with a depressive disorder in later life

OBJECTIVES: Polypharmacy and late-life depression often congregate in the geriatric population. The primary objective is to identify determinants of polypharmacy in patients with depression, and second to examine polypharmacy in relation to various clinical phenotypes of depression and its course. METHODS: A longitudinal observational study using data of the Netherlands Study of Depression in Older persons (NESDO) including 375 patients with depression ≥ 60 years and 132 non-depressed comparisons. Linear and logistic regression were used to analyze both polypharmacy (dichotomous: ≥ 5 medications) and number of prescribed drugs (continuous) in relation to depression, various clinical phenotypes, and depression course. RESULTS: Polypharmacy was more prevalent among patients with depression (46.9%) versus non-depressed comparisons (19.7%). A lower level of education, lower cognitive functioning, and more chronic diseases were independently associated with polypharmacy. Adjusted for these determinants, polypharmacy was associated with a higher level of motivational problems, anxiety, pain, and an earlier age of onset. A higher number of drugs was associated with a worse course of late-life depression (OR=1.24 [95% CI: 1.03 - 1.49], p=.022). CONCLUSION: Older patients with depression have a huge risk of polypharmacy, in particular among those with an early onset depression. As an independent risk factor for chronic depression, polypharmacy needs to be identified and managed appropriately. Findings suggest that depression moderates polypharmacy through shared risk factors, including motivational problems, anxiety, and pain. The complex interaction with somatic health burden requires physicians to prescribe medications with care

Conjugacy and rigidity for nonpositively curved manifolds of higher rank

AbstractLet M and N be compact Riemannian manifolds with sectional curvature K ⩽ 0 such that M has dimension ⩾ 3 and rank ⩾ 2. If there exists a C0 conjugacy F between the geodesic flows of the unit tangent bundles of M and N, then there exists an isometry G: M → N that induces the same isomorphism as F between the fundamental groups of M and N

Long-term effectiveness and prediction of treatment outcome in cognitive behavioral therapy and sertraline for late-life anxiety disorders

Background: Although anxiety disorders are prevalent in older adults, randomized controlled trials of treatment effectiveness for late-life anxiety are scarce and have focused primarily on the effectiveness of psychotherapeutic interventions. However, recent findings suggest that in some cases, pharmacological treatment may be more beneficial for late-life anxiety disorders. As yet, there have been no systematic studies investigating prognostic factors for the outcome of cognitive behavioral therapy (CBT) and pharmacotherapy for late-life anxiety. The objective of the present study was to study long-term treatment outcomes and to explore differential predictors for both short-term and long-term treatment outcomes of sertraline and CBT for late-life anxiety disorders. Methods: Participants of a randomized controlled trial (RCT) comparing sertraline and CBT for the treatment of late-life anxiety were contacted one year after completing their treatment, so that predictors for both short-term and long-term treatment outcome could be established. Results: Sertraline showed a greater reduction of symptoms than CBT on anxiety (Hamilton Anxiety Rating Scale; HARS) and worry (Worry Domain Questionnaire) ratings at one-year follow-up. The strongest predictor for short-term CBT outcome was poor perceived health, explaining 40% of the variance in post-treatment residual gain scores on the HARS. The strongest predictor for long-term CBT outcome was neuroticism, explaining 20% of the variance in residual gain scores at one-year follow-up. Analyses revealed no significant predictors for treatment outcome in sertraline participants. Conclusions: Our study suggests that long-term use of sertraline might be more beneficial for late-life anxiety than a 15-week CBT program. Poor perceived health and neuroticism are predictive of less improvement after CBT in anxious older adults. Implications of these findings are discussed

Vitamin D deficiency and course of frailty in a depressed older population

Objective: To study the association between vitamin D levels and frailty, its components and course in a depressed sample. Methods: Baseline and two-year follow-up data from the depressed sample of the Netherlands Study of Depression in Older persons (NESDO), a prospective observational cohort study, were analyzed. The 378 participants (aged 60–93) had a diagnosis of depression according to DSM-IV criteria. Frailty was defined according to Fried’s physical phenotype. 25-OH vitamin D measurement was performed by liquid chromatography–tandem mass spectrometry. Linear and logistic regression analyses were performed, adjusted for covariates. Results: Higher vitamin D levels were cross-sectionally associated with lower prevalence of frailty (OR 0.64 [95%-CI 0.45–0.90], p =.010), predicted a lower incidence of frailty among non-frail depressed patients (OR 0.51 [95%-CI 0.26–1.00], p=.050), and, surprisingly, the persistence of frailty among frail depressed patients (OR 2.82 [95%-CI 1.23–6.49], p=.015). Conclusions: In a depressed population, higher vitamin D levels were associated with lower prevalence and incidence of frailty. Future studies should examine whether the favorable effect of low vitamin D levels on the course of frailty can be explained by confounding or whether unknown pathophysiological mechanisms may exert protective effects

Symptomatic and functional recovery in depression in later life

Objectives: Functional limitations give an indication of the total impact of diseases, such as depression, on individuals health and recovery. This study examines the change in several domains of functioning over 2 years in older persons depressed at baseline (non-remitted group and remitted group after 2 years) and in a non-depressed comparison group. Methods: Data were used from a cohort study (Netherlands Study of Depression in Older persons [NESDO]) consisting of depressed older persons ≥ 60 years (N = 378) and a non-depressed comparison group (N = 132) with 2 years of follow-up (attrition rate 24%). Functional limitations (outcome) were assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire every 6 months. Total scores and domain scores were used. Depression was classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria at baseline and at 2-year follow-up. Severity of depression (predictor) was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Results: Linear mixed models showed that the level of functional limitations differed between the three groups during 2 years of follow-up. The non-remitted group had the highest level of functional limitations during 2 years, followed by the remitted group. Stable low levels of functional limitations were found for the non-depressed group. Remission from depression was accompanied by improvements in functioning, however, compared to the non-depressed comparison group significant functional limitations remained. Higher severity of depression appeared as risk factor for a declining course of functioning, especially the social aspects of functioning. Methodological considerations: Participants that were more severely depressed and more functionally impaired at baseline had higher attrition rates than the participants that were included in the analytical sample. Conclusion: This study showed that depression in later life has long-term debilitating effects on functioning, enduring even after remission from depression. This implies that depression treatment in later life should aim broader than just symptomatic recovery, but also include functional recovery

Vitamin D Status and Depressive Symptoms in Older Adults:A Role for Physical Functioning?

Objectives: Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms. Methods: Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995–2002) and a younger-old cohort (55–65 years, n = 737, assessed from 2002–2009). Measurements: Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models. Results: Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations >75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed. Conclusions: Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed

The importance of personality and life-events in anxious depression:From trait to state anxiety

Objectives: Anxious depression is associated with severe impairment and bad prognoses. We hypothesize that recent life-events are associated with more anxiety in late-life depression and that this is conditional upon the level of certain personality traits. Method: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used. In 333 patients (>= 60 years) suffering from a major depressive disorder, anxiety was assessed with the BAI, personality traits with the NEO-FFI and the Mastery Scale, and life-events with the Brugha questionnaire. Multiple linear regression analyses were applied with anxiety severity as dependent and life-events and personality traits as independent variables. Results: 147 patients (44.1%) had recently experienced one or more life-events. The presence of a life-event is not associated with anxiety (p = .161) or depression severity (p = .440). However, certain personality traits interacted with life-events in explaining anxiety severity. Stratified analyses showed that life-events were associated with higher anxiety levels in case of high levels of neuroticism and openness and low levels of conscientiousness or mastery. Conclusions: In the face of a life-event, personality traits may play a central role in increased anxiety levels in late-life depression

Long-term exposure to anticholinergic and sedative medications and cognitive and physical function in later life

Background: Anticholinergic and sedative medications are frequently prescribed to older individuals. These medications are associated with short-term cognitive and physical impairment, but less is known about long-term associations. We therefore examined over twenty years whether cumulative exposure to these medications was related to poorer cognitive and physical functioning. Methods: Older adult participants of the Longitudinal Aging Study Amsterdam (LASA) were followed from 1992-2012. On 7 measurement occasions, cumulative exposure to anticholinergic and sedative medications was quantified with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Cognitive functioning was assessed with the Mini Mental State Examination (MMSE), Alphabet Coding Task (ACT, 3 trials), Auditory Verbal Learning Test (AVLT, learning and retention condition), and Raven Colored Progressive Matrices (RCPM, 2 trials). Physical functioning was assessed with the Walking Test (WT), Cardigan Test (CT), Chair Stands Test (CST), Balance Test (BT), and self-reported Functional Independence (FI). Data were analyzed with linear mixed models adjusted for age, education, sex, living with a partner, BMI, depressive symptoms, co-morbidities (cardiovascular disease, diabetes, cancer, COPD, osteoarthritis, CNS diseases), and prescribed medications. Results: Longitudinal associations were found of the DBI with poorer cognitive functioning (less items correct on the 3 ACT trials, AVLT learning condition, and the 2 RCPM trials) and with poorer physical functioning (longer completion time on the CT, CST, and lower self-reported FI). Conclusions: This longitudinal analysis of data collected over 20 years, showed that higher long-term cumulative exposure to anticholinergic and sedative medications was associated with poorer cognitive and physical functioning