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Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic-pituitary-adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non-depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7-8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty-two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration., (© 2017 European Sleep Research Society.)

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

Background: Late-life depression is thought to differ in clinical presentation from early-life depression. Particularly, late-life depression is considered to be more characterized by apathy than is early-life depression. Lacking convincing evidence, this study examines the presence and associated socio-demographic/clinical characteristics of apathy in older compared to younger depressed persons., Methods: This cross-sectional study used data from two naturalistic cohort studies, i.e. the Netherlands Study of Depression in Older Persons (NESDO) and the Netherlands Study of Depression and Anxiety (NESDA). These studies included 605 persons (aged 18-93 years) with a major depressive disorder, divided into 217 early-life (< 60 years) and 388 late-life (≥ 60 years) depressed persons. Apathy was considered present if a score of ≥14 on the Apathy Scale., Results: Apathy was strongly associated with age: it was more frequently present in persons with late-life depression (74.5%) than in those with early-life depression (53.5%). Independent of age, the following characteristics were associated with the presence of apathy: male gender, low education, use of benzodiazepines, chronic diseases, and more severe depression. Of all potential risk factors, only former and current smoking was associated with the presence of apathy in older depressed persons but not in younger depressed persons (p-value for age interaction = 0.01)., Limitations: No causal relationships can be drawn due to the cross-sectional design of the study., Conclusions: In depressed individuals, clinically relevant apathy was more frequently present in older compared to younger persons. Both age groups showed largely the same associated risk factors. Apathy was independently associated with older age, male gender and more severe depression., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The occurrence of well-established risk factors for depression differs across the lifespan. Risk factors may be more strongly associated with depression at ages when occurrence, and therefore expectance, is relatively low ("on-time off-time" hypothesis). This large-scale study examined absolute and relative risks of established risk factors for depression across the lifespan., Methods: Participants were 2,215 currently or never depressed adults aged 18 to 93 years from two cohort studies: NESDA and NESDO. The occurrence of 19 established risk factors (absolute risk) was examined in different age groups. In addition, the relative risk of these risk factors for depression was compared across age groups by examining risk factor × age interaction., Results: The occurrence of all risk factors differed significantly across age groups. Although most risk factors had significant associations with depression across the lifespan, for five risk factors the strength of the association was age-dependent. Stronger associations with depression in younger age were found for childhood abuse, pain, higher body mass index (BMI) and number of chronic diseases, whereas low income imposed a stronger risk in older age. Associations with depression were strongest in age groups where occurrence was lowest., Conclusions: Although the exposure to risk factors changes across the lifespan, the relative risk associating them to depression remains similar for most risk factors. Some specific risk factors (low income, and health factors pain, BMI, and number of chronic diseases), however, seem more strongly associated with depression in ages in which occurrence is lowest and least expected., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women., Methods: In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months., Results: Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level < 8 nmol/L, of whom 8 suffered from MDD. In women, hormone levels showed no significant difference between the groups. In men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (β = -0.15, t(151) = -2.15, p = 0.03)., Conclusion: Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: To gain new insights for support for older people with low mood, we explored the perceptions of 'screenpositive' older people on underlying causes and possible solutions., Design and Method: We conducted two in-depth interviews with 38 participants (≥77 years) who screened positive for depressive symptoms in general practice. To investigate the influence of the presence of complex health problems, we included 19 persons with and 19 without complex problems. Complex problems were defined as a combination of functional, somatic, psychological or social problems., Results: All participants used several cognitive, social or practical coping strategies. Four patterns emerged: mastery, acceptance, ambivalence, and need for support. Some participants, especially those with complex problems, were ambivalent about possible interventions., Conclusion: Most older participants perceived their coping strategies as sufficient. General practitioners can support self-management by exploring the (effectiveness of) personal coping strategies, providing information, elaborating on perceptions of risks and discussing alternative options with older persons.

The accuracy of cerebral blood flow measurements using pseudo-continuous arterial spin labeling can be affected by vascular factors other than cerebral blood flow, such as flow velocity and arterial transit time. We aimed to elucidate the effects of common variations in vascular anatomy of the circle of Willis on pseudo-continuous arterial spin labeling signal. In addition, we investigated whether possible differences in pseudo-continuous arterial spin labeling signal could be mediated by differences in flow velocities. Two hundred and three elderly participants underwent magnetic resonance angiography of the circle of Willis and pseudo-continuous arterial spin labeling scans. Mean pseudo-continuous arterial spin labeling-cerebral blood flow signal was calculated for the gray matter of the main cerebral flow territories. Mean cerebellar gray matter pseudo-continuous arterial spin labeling-cerebral blood flow was significantly lower in subjects having a posterior fetal circle of Willis variant with an absent P1 segment. The posterior fetal circle of Willis variants also showed a significantly higher pseudo-continuous arterial spin labeling-cerebral blood flow signal in the ipsilateral flow territory of the posterior cerebral artery. Flow velocity in the basilar artery was significantly lower in these posterior fetal circle of Willis variants. This study indicates that pseudo-continuous arterial spin labeling measurements underestimate cerebral blood flow in the posterior flow territories and cerebellum of subjects with a highly prevalent variation in circle of Willis morphology. Additionally, our data suggest that this effect is mediated by concomitant differences in flow velocity between the supplying arteries., (© The Author(s) 2016.)

Objectives: To identify clinically relevant subtypes of apathy in older persons using latent class analysis (LCA) and investigate the distribution of different characteristics across these subtypes., Measurements: Cross-sectional data of 122 older persons (mean age 84 years, 60% female) participating in the general population-based PROactive Management Of Depression in the Elderly study, with apathy according to a score of 14 or higher on the Apathy Scale, were included for LCA. All 14 items of the Apathy Scale were used as indicator variables. Several characteristics were examined including sociodemographics, depressive, and anxiety symptoms; global cognitive function; quality of life indicators; hazardous alcohol intake (drinking ≥ 14 consumptions per week); and perceived chronic pain., Results: Three distinct LCA classes were found classifying 17%, 7%, and 76% of the participants respectively. Individuals in the first class had a higher level of education and were less likely to live alone. Those in the second class had higher apathy and depression scores, lived more frequently alone and used more alcohol. Individuals in the third class showed a lower level of education and worse cognitive function. In multivariable multinomial analyses, only a lower educational level and higher scores on the Apathy Scale were significant predictors for class membership., Conclusion: Differences between LCA-derived classes were minimal, suggesting that in a general population-based cohort the Apathy Scale measures a homogeneous construct. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials., Objective: to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment., Methods: a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses., Results: at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]., Conclusion: in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Metabolic changes have been frequently associated with Huntington's disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington's disease patients especially when brain or other tissue samples are difficult to collect., Objectives: We investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabolomics data with our previously published next generation sequencing-based gene expression data from the same patients in order to interconnect the metabolomics changes with transcriptional alterations., Methods: This analysis was performed using targeted metabolomics and flow injection electrospray ionization tandem mass spectrometry in 133 serum samples from 97 Huntington's disease patients (29 pre-symptomatic and 68 symptomatic) and 36 controls., Results: By comparing HD mutation carriers with controls we identified 3 metabolites significantly changed in HD (serine and threonine and one phosphatidylcholine-PC ae C36:0) and an additional 8 phosphatidylcholines (PC aa C38:6, PC aa C36:0, PC ae C38:0, PC aa C38:0, PC ae C38:6, PC ae C42:0, PC aa C36:5 and PC ae C36:0) that exhibited a significant association with disease severity. Using workflow based exploitation of pathway databases and by integrating our metabolomics data with our gene expression data from the same patients we identified 4 deregulated phosphatidylcholine metabolism related genes ( ALDH1B1 , MBOAT1 , MTRR and PLB1 ) that showed significant association with the changes in metabolite concentrations., Conclusion: Our results support the notion that phosphatidylcholine metabolism is deregulated in HD blood and that these metabolite alterations are associated with specific gene expression changes.

Importance: Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function., Objective: To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning., Design, Setting, and Participants: A community-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-up was performed at 128 general practices in the Netherlands. A total of 385 participants 75 years or older with mild cognitive deficits (Mini-Mental State Examination score, 21-27) without serious cardiovascular disease who received antihypertensive treatment were enrolled in the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26, 2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat analyses were performed from January 20 through April 11, 2014., Interventions: Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment (allocation ratio, 1:1)., Main Outcomes and Measures: Change in the overall cognition compound score. Secondary outcomes included changes in scores on cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen Activity Restriction Scale (functional status), and Cantril Ladder (quality of life)., Results: Compared with 176 participants undergoing analysis in the control (continuation) group, 180 in the intervention (discontinuation) group had a greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg; P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The intervention group did not differ from the control group in change (95% CI) in overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14]; difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did not differ significantly in secondary outcomes, including differences (95% CIs) in change in compound scores of the 3 cognitive domains (executive function, -0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99; P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [-1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]). Adverse events were equally distributed., Conclusions and Relevance: In older persons with mild cognitive deficits, discontinuation of antihypertensive treatment did not improve cognitive, psychological, or general daily functioning at the 16-week follow-up., Trial Registration: trialregister.nl Identifier: NTR2829.

Patients with long-term remission of Cushing's disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. Earlier magnetic resonance imaging (MRI) studies demonstrated abnormalities of brain structure and resting-state connectivity in patients with long-term remission of CD, but no data are available on functional alterations in the brain during the performance of emotional or cognitive tasks in these patients. We performed a cross-sectional functional MRI study, investigating brain activation during emotion processing in patients with long-term remission of CD. Processing of emotional faces versus a non-emotional control condition was examined in 21 patients and 21 matched healthy controls. Analyses focused on activation and connectivity of two a priori determined regions of interest: the amygdala and the medial prefrontal-orbitofrontal cortex (mPFC-OFC). We also assessed psychological functioning, cognitive failure, and clinical disease severity. Patients showed less mPFC activation during processing of emotional faces compared to controls, whereas no differences were found in amygdala activation. An exploratory psychophysiological interaction analysis demonstrated decreased functional coupling between the ventromedial PFC and posterior cingulate cortex (a region structurally connected to the PFC) in CD-patients. The present study is the first to show alterations in brain function and task-related functional coupling in patients with long-term remission of CD relative to matched healthy controls. These alterations may, together with abnormalities in brain structure, be related to the persisting psychological morbidity in patients with CD after long-term remission., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Dispositional optimism, a personality trait characterized by generalized positive expectations towards the future, is thought to remain rather stable over time. It is however largely unknown to what extent affective disorders and its risk factors affect dispositional optimism., Methods: We examined the association between (lifetime) affective disorders and childhood trauma with dispositional optimism in a sample of 2104 subjects (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA). Dispositional optimism was measured with the Life Orientation Test Revised (LOT-R). Diagnoses of depressive and anxiety disorders were based on the Composite Interview diagnostic Instrument (CIDI).Childhood trauma was assessed using the Childhood Trauma Interview (CTI) and life-events with the List of Threatening Events Questionnaire (LTQ)., Results: The 2104 participants were on average 46.0 (SD 13.1) years old and 65.8% were female. Multivariate analyses showed that dispositional optimism was inversely associated with current affective disorders (depression: B=-1.089 and anxiety: B=-1.066, both p<0.001), but also with remitted affective disorders (depression: B=-0.822 and anxiety: B=-0.558, both p<0.001) and severity of depression (B=-4.230; p<0.001). A history of childhood emotional maltreatment (B=-0.905, p<0.001) was related to lower optimism, whilst positive life-events were associated with higher levels of optimism (B=0.235, p>0.001)., Limitations: The cross-sectional design hampers inferences about causality., Conclusion: Lower levels of dispositional optimism are associated with stage of affective disorders, even after remission, and a history of childhood emotional maltreatment. Identification of the risk factors contributes to understand fluctuations in dispositional optimism., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: To explore the decision-making process involving elderly subjects with mild cognitive impairment and a relative when asked to participate in a clinical trial., Design, Setting, and Participants: In this qualitative study, we investigated the decision-making process during the informed consent conversations between the researchers of a clinical trial and 18 persons aged 75 years and older, with a Mini-Mental State Examination score ≥21 and ≤27. This assessment was performed by both observation and a standardized interview with the older person and a close relative who could act as a proxy (surrogate) decision maker, if necessary. The informed consent conversation and procedure took place at the home of the potential participants., Measurements: Videotapes or audiotapes were transcribed and analyzed by using coding schemes., Results: The participants were able to formulate substantial reasons why they would want to participate in the clinical trial. Willingness to help others and contribute to medical knowledge, combined with the absence of substantial risks, were predominant reasons for participation. Most older subjects did consult their relatives, who generally considered them capable of deciding for themselves., Conclusions: Notwithstanding their (mild) cognitive impairment, these older subjects were able to formulate substantiated reasons for participation in a clinical trial. Thus, it is plausible that they were capable of making this decision themselves, which was affirmed by their relatives. Recognition of the desire to contribute unselfishly to research that might benefit others has important implications for future clinical research conducted in older people with mild cognitive impairment., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare alcohol use between depressed and nondepressed older adults, and to investigate correlates of alcohol abstinence and at-risk alcohol consumption in depressed older adults., Design: Cross-sectional study., Setting: Netherlands Study of Depression in Older Persons (NESDO)., Participants: A total of 373 participants (mean [standard deviation] age: 70.6 [7.3] years; 66% women) diagnosed with a depressive disorder, and 128 nondepressed participants., Measurements: Alcohol use was assessed with the Alcohol Use Disorders Identification Test (AUDIT). Participants were categorized into abstainers (AUDIT score: 0), moderate drinkers (AUDIT score: 1-4), and at-risk drinkers (AUDIT score: ≥5). Multinomial logistic regression analysis was performed with AUDIT categories as outcome, and demographic, social, somatic, and psychological variables as determinants., Results: The depressed group consisted of 40.2% abstainers, 40.8% moderate drinkers, and 19.0% at-risk drinkers. The depressed participants were more often abstinent and less often moderate drinkers than the nondepressed participants; they did not differ in at-risk drinking. Depressed abstainers more often used benzodiazepines but less often used antidepressants, and they had a poorer cognitive function than depressed moderate drinkers. Depressed at-risk drinkers were more often smokers and had fewer functional limitations but more severe depressive symptoms than depressed moderate drinkers., Conclusions: Although alcohol abstinence was more common in depressed than in nondepressed older adults, 19% of depressed persons were at-risk drinkers. Because at-risk drinking is associated with more severe depression and may have a negative impact on health and treatment outcome, it is important that physicians consider alcohol use in depressed older adults., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between apathy and perceived quality of life in groups both with and without depressive symptoms or cognitive impairment., Methods: We conducted a cross-sectional study comparing quality of life in older persons with and without apathy in 19 Dutch general practices. Participants were 1,118 older persons aged at least 75 years without current treatment for depression and a Mini-Mental State Examination score of at least 19. Perceived quality of life was determined using Cantril's Ladder for overall quality of life, EuroQol (EQ)-5D thermometer for subjective health quality, and De Jong-Gierveld Loneliness questionnaire for perceived loneliness. Apathy was assessed with the Apathy Scale., Results: Of the 1,118 older persons, apathy was present in 122 (11%) of them. Overall, apathy was associated with having no work, lower level of education, presence of depressive symptoms, cognitive impairment, and decreased scores on all quality of life measures. Among the 979 (88%) older persons without depressive symptoms and cognitive impairment, apathy was present in 73 (7.5%) of them, showing similar associations as in the total population. In the 77 (7%) persons with cognitive impairment only, apathy was correlated to a lower score on the EQ-5D thermometer. However, in the 51 (5%) depressed persons without cognitive impairment, presence of apathy did not contribute to their decreased quality of life., Conclusion: Apathy frequently occurred in community-dwelling older persons, also in the absence of depressive symptoms and cognitive impairment. In them, apathy contributed to the perception of a diminished quality of life in various aspects of daily life., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the role of childhood abuse in late-life depression. The aim of the study is therefore to study whether childhood abuse is associated with late-life depression according to its onset, and which clinical characteristics play a role in this association., Methods: Data were used from 378 depressed and 132 non-depressed persons, aged 60-93 years, from the Netherlands Study of Depression in Older persons (NESDO). Childhood abuse included psychological, physical and sexual abuse and emotional neglect., Results: 53% of the depressed older adults reported childhood abuse, compared to 16% of the non-depressed older adults (p<0.001). Using logistic regression analyses adjusted for age, sex and level of education, depression was strongest associated with physical abuse (Odds Ratio ((OR) 13.71; 95% Confidence Interval (CI) 3.25-57.91) and least with sexual abuse (OR 5.35; 95% CI 2.36-12.14). Childhood abuse was associated with early-onset (OR 13.73, 95% CI 7.31-25.80), middle age-onset (OR 5.36, 95% CI 2.90-9.90) and late-onset depression (OR 4.74, 95% CI 2.51-8.95). In the late-onset group childhood abuse was associated with an increased number of chronic diseases., Limitations: Age of depression onset and childhood abuse were asked retrospectively, which may have biased the results., Conclusions: Childhood abuse is strongly related to late-life depression and its comorbidities, even in the case of late-onset depression. This might suggest that psychological wellbeing can be maintained throughout middle age, but may be disturbed in later life., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To investigate the performance and usability of the Six-Item Cognitive Impairment Test (6CIT) as a screening instrument for cognitive impairment in older, general hospital inpatients/outpatients., Method: In 253 general hospital patients aged ≥ 70 years, diagnostic accuracy of the 6CIT and time required to administer it were assessed using the Mini-Mental State Examination (MMSE) as the criterion standard., Results: The (negative) correlation between the 6CIT and the MMSE was very high (r = -0.82). Optimal comparability was found using a MMSE cutoff of ≤19 for lower and ≤23 for higher educated patients, at a cutoff of ≥11 on the 6CIT that was not sensitive to educational level. The sensitivity of the 6CIT was 0.90 and the specificity was 0.96, whereas the positive predictive value was 0.83 and the negative predictive value was 0.98. The area under the curve was 0.95. The mean administration time was 5.8 min for the MMSE and 2.5 min for the 6CIT (p ≤ 0.01)., Conclusions: Diagnostic accuracy of the 6CIT was high. As the 6CIT is not sensitive to educational level, does not require advanced language skills, only takes a few minutes to administer and is very easy to use, it appears to be a suitable screening instrument for cognitive impairment in older patients in the general hospital., (Copyright © 2011 John Wiley & Sons, Ltd.)

Many rating scales can be self-administered or interviewer-administered, and the influence of administration method on scores is unclear. We aimed to study this influence on scores of the Geriatric Depression Scale (GDS-15), used as a screening instrument in general practice. In two general practices 376 registered patients aged 75 years and older were asked to participate. Exclusion criteria were dementia and current treatment for depression. The GDS-15 was administered twice within 1 month: self-administered by mail, and interviewer-administered during home visits. The sequence of administering the methods was different for the two practices. We analyzed differences in total and item GDS-scores. Of 141 subjects who participated (response rate 55%) 59 were men (42%). Mean age was 81.4 years (SD 4.8). When the GDS-15 was self-administered, 33 subjects (23.4%) left items unanswered. There were no items unanswered when the GDS-15 was interviewer-administered. On average the self-administered total GDS scores were 0.70 points higher than interviewer-administered scores (95% confidence interval=0.41; 0.98), with a large range of variation in the scores (limits of agreement -2.69 to 4.08). Item-item comparisons showed high percentages of agreement. Chance-corrected agreement (kappa) was moderate to fair, but three items showed only slight agreement (kappa values <0.21). In conclusion, compared to interviewer-administered scores, scores on the GDS-15 when self-administered were higher. The method of administration should be taken into account when interpreting scores., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Dispositional optimism, defined as a generalized tendency to positive outcome expectancies, is associated with well-being and successful aging. However, it remains unclear whether optimism is also correlated to less feelings of loneliness over time. We aimed to determine whether dispositional optimism is prospectively associated with less feelings of loneliness, independently of potential confounders inherent to the aging process., Methods: We observed 416 older men aged between 70 and 89 years (mean 74.9 years, standard deviation [SD] 4.7 years) within the population-based Zutphen Elderly Study during 10 years of follow-up. Baseline dispositional optimism was assessed using a four-item questionnaire. The presence of feelings of loneliness, the main outcome of our study, was assessed using the 11-item loneliness scale of De Jong Gierveld in the years 1990, 1993, 1995, and 2000. The association between baseline dispositional optimism and loneliness over time was tested by using multilevel regression analysis and by adjusting for potential confounders (i.e. age, living arrangement, social contacts, widowhood, memberships, self-rated health, and depressive symptoms)., Results: Feelings of loneliness significantly increased during 10 years of follow-up but showed temporal stability (reliability coefficient 0.78). Low baseline dispositional optimism was strongly associated with loneliness over time, also in the adjusted analysis. A 1 SD increase in baseline dispositional optimism was associated with a 0.14 SD (95% confidence interval 0.04-0.23) lower level of loneliness (F(1,320)  = 7.8; p = 0.006)., Conclusions: Dispositional optimism is correlated to lower feelings of loneliness over time in older men, independently of depression or changes in social network., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to have an important role in the development of delirium. We aimed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients., Methods: Patients (aged ≥18 years) who were diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated between November, 2008, and January, 2010. Patients were randomised (1:1 ratio) to receive an increasing dose of rivastigmine or placebo, starting at 0·75 mL (1·5 mg rivastigmine) twice daily and increasing in increments to 3 mL (6 mg rivastigmine) twice daily from day 10 onwards, as an adjunct to usual care based on haloperidol. The trial pharmacist generated the randomisation sequence by computer, and consecutively numbered bottles of the study drug according to this sequence to conceal allocation. The primary outcome was the duration of delirium during hospital admission. Analysis was by intention to treat. Duration of delirium was censored for patients who died or were discharged from hospital while delirious. Patients, medical staff, and investigators were masked to treatment allocation. Members of the data safety and monitoring board (DSMB) were unmasked and did interim analyses every 3 months. This trial is registered with ClinicalTrials.gov, number NCT00704301., Findings: Although a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n=54 on rivastigmine, n=50 on placebo), the DSMB recommended that the trial be halted because mortality in the rivastigmine group (n=12, 22%) was higher than in the placebo group (n=4, 8%; p=0·07). Median duration of delirium was longer in the rivastigmine group (5·0 days, IQR 2·7-14·2) than in the placebo group (3·0 days, IQR 1·0-9·3; p=0·06)., Interpretation: Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients., Funding: ZonMw, the Netherlands Brain Foundation, and Novartis., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: Chronic obstructive pulmonary disease (COPD) has been associated with depression in middle-aged and younger old adults. However, it remains unknown whether COPD contributes to the occurrence of depressive symptoms in the oldest old subjects. The authors aimed to determine whether oldest old persons with COPD are at increased risk of developing depressive symptoms., Design, Setting, Participants: The authors prospectively followed up 333 subjects from age 85 years onward within the population-based Leiden 85-plus Study. COPD, along with other chronic diseases, was assessed using structured questionnaires and confirmed with the diagnosis of the treating physician. Depressive symptoms were assessed annually using the 15-item version of the Geriatric Depression Scale (GDS-15). Nondepressed subjects with and without COPD at baseline were compared for the occurrence of depressive symptoms during 5 years of follow-up using multilevel analysis., Results: At baseline, COPD was present in 40 subjects (12%) and associated with male gender, lower education, and smoking. During 5 years of follow-up, an additional annual increase of 0.29 points (standard error [SE] = 0.14) in the GDS-score was observed in subjects with COPD, when compared with those without COPD (F[1, 212] = 4.1, p = 0.04). This difference persisted after adjustment for demographics, baseline GDS score, functional limitations, and presence of chronic diseases (F[1, 451] = 4.6, p = 0.03)., Conclusion: In the oldest old subjects, COPD independently contributes to an increased risk of developing depressive symptoms. Clinicians should be aware of the association of COPD with depressive symptoms in the oldest old to offer them optimal treatment in an early stage.

Objective: To examine the temporal relation between depression and cognitive impairment in old age., Design: Prospective, population based study with four years of follow up., Setting: City of Leiden, the Netherlands., Participants: 500 people aged 85 years at recruitment., Main Outcome Measures: Annual assessments of depressive symptoms (15 item geriatric depression scale), global cognitive function (mini-mental state examination), attention (Stroop test), processing speed (letter digit coding test), and immediate and delayed recall (12 word learning test)., Results: At 85 years old, participants' depressive symptoms and cognitive impairment were highly significantly correlated (P < 0.001). During follow up, an accelerated annual increase of depressive symptoms was associated with impaired attention (0.08 points (95% confidence interval 0.01 to 0.16)), immediate recall (0.17 points (0.09 to 0.25)), and delayed recall (0.10 points (0.02 to 0.18)) at baseline. In contrast, depressive symptoms at baseline were not related to an accelerated cognitive decline during follow up (P > 0.05)., Conclusion: Caregivers should be aware of the development of depressive symptoms when cognitive impairment is present. However, the presence of depression only does not increase the risk of cognitive decline.