Search

Background and purpose: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. Methods: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. Results: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27–0.88; and RD 1.39; CI − 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23–0.80; and RD 9.05; CI 2.78–15.32). Conclusions: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis.Methods: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors.Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)].Conclusions: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 . [ABSTRACT FROM AUTHOR]

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+. Addition of the TAC or heart valve score did not improve risk predictions. [ABSTRACT FROM AUTHOR]

Objective To estimate the association between hippocampal and total brain volume and the course of depressive symptoms over eight years of follow-up in patients with a history of vascular disease. Method Within the SMART-Medea study, 636 participants (62 ± 10 years) had a 1.5-tesla brain MRI obtaining hippocampal and total brain volumes. Depressive symptoms were assessed with the Patient Health Questionnaire-9 biannually during eight-year follow-up. Generalized estimating equation models with robust standard errors were used to assess the associations of hippocampal and total brain volumes with depressive symptoms during follow-up adjusting for age, sex, education, and intracranial volume. An interaction term between volume and time (6-month intervals) was included to examine whether the course of depressive symptoms differed according to hippocampal and total brain volume. Results The mean PHQ-9 score was 2.8 ± 3.5. Smaller hippocampal volumes were associated with an increasing course of depressive symptom levels, while larger volumes were associated with decreasing levels ( P-value interaction = 0.07). Smaller total brain volume was associated with consistently higher levels of depressive symptoms, but not with change in course of depressive symptoms ( P-value interaction = 0.45). Conclusion Smaller hippocampal volume but not total brain volume is associated with poorer course of depressive symptoms over eight years of follow-up. [ABSTRACT FROM AUTHOR]

BackgroundDepressive symptoms and cognitive impairment often co-occur, but their interactive relationship is complex and the direction of causation is still a topic of research. We examined the influence of cognitive performance on the course of depressive symptoms during 7 years of follow-up in patients with vascular disease.MethodWithin the SMART-MR study, 736 patients (mean age 62 ± 10 years) had neuropsychological assessment on four cognitive domains at baseline [memory (MEM), working memory (WMEM), executive functioning (EXEC), and information processing speed (SPEED)]. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline and every 6 months during 7 years of follow-up. Generalized Estimating Equation (GEE) models were used to assess the association between cognitive performance with depressive symptoms at multiple time points during follow-up. Interaction terms between the respective cognitive domains and time was included to examine if the course of depressive symptoms differed according to baseline cognitive performance.ResultsThe GEE analyses showed no significant interactions between the respective cognitive domains and time indicating no different course of depressive symptoms according to baseline cognitive performance. Lower MEM, EXEC or SPEED, but not WMEM performance, was significantly associated with more depressive symptoms during follow-up per z score decrease: MEM [B = 0.70, 95% confidence interval (CI) 0.35–1.05]; EXEC (B = 0.88, 95% CI 0.41–1.36), and SPEED (B = 0.57, 95% CI 0.21–0.92).ConclusionsPoorer cognitive performance on the domains MEM, EXEC and SPEED, but not WMEM, was associated with higher levels of depressive symptoms over 7 years of follow-up, but not with a different course of depressive symptoms over time. [ABSTRACT FROM AUTHOR]

BackgroundSeveral studies have reported weak associations between religious or spiritual belief and psychological health. However, most have been cross-sectional surveys in the USA, limiting inference about generalizability. An international longitudinal study of incidence of major depression gave us the opportunity to investigate this relationship further.MethodData were collected in a prospective cohort study of adult general practice attendees across seven countries. Participants were followed at 6 and 12 months. Spiritual and religious beliefs were assessed using a standardized questionnaire, and DSM-IV diagnosis of major depression was made using the Composite International Diagnostic Interview (CIDI). Logistic regression was used to estimate incidence rates and odds ratios (ORs), after multiple imputation of missing data.ResultsThe analyses included 8318 attendees. Of participants reporting a spiritual understanding of life at baseline, 10.5% had an episode of depression in the following year compared to 10.3% of religious participants and 7.0% of the secular group (p < 0.001). However, the findings varied significantly across countries, with the difference being significant only in the UK, where spiritual participants were nearly three times more likely to experience an episode of depression than the secular group [OR 2.73, 95% confidence interval (CI) 1.59–4.68]. The strength of belief also had an effect, with participants with strong belief having twice the risk of participants with weak belief. There was no evidence of religion acting as a buffer to prevent depression after a serious life event.ConclusionsThese results do not support the notion that religious and spiritual life views enhance psychological well-being. [ABSTRACT FROM PUBLISHER]

Objective To investigate the independent effects of antihypertensive treatment and blood pressure ( BP) levels on physical and mental health status in patients with arterial disease. Design and setting Cross-sectional analyses were conducted within the single-centre Secondary Manifestations of ARTerial disease ( SMART) study, in a hospital care setting. Subjects A total of 5877 patients (mean age 57 years) with symptomatic and asymptomatic arterial disease underwent standardized vascular screening. Main outcome measure The primary outcome was self-rated physical and mental health assessed using the 36-item short-form health survey. Results In the total population, antihypertensive drug use and increased intensity of antihypertensive treatment were associated with poorer health status independent of important confounders including BP levels; adjusted mean differences [95% confidence interval ( CI)] in physical and mental health between n = 0 and n ≥ 3 antihypertensives were −1.2 (−2.1; −0.3) and −3.5 (−4.4; −2.6), respectively. Furthermore, both lower systolic and lower diastolic BP levels were related to poorer physical and mental health status independent of antihypertensive treatment. Mean differences (95% CI) in physical and mental health status per SD decrease in systolic BP were −0.56 (−0.84; −0.27) and −0.32 (−0.61; −0.03) and per SD decrease in diastolic BP were −0.50 (−0.78; −0.23) and −0.08 (−0.36; 0.20), respectively. The association between low BP and poor health status was particularly present in patients with coronary artery disease. Conclusions In a population of patients with asymptomatic and symptomatic arterial disease, antihypertensive treatment and lower BP levels are independently associated with poorer self-rated physical and mental health. These findings suggest that different underlying mechanisms may explain these independent associations. [ABSTRACT FROM AUTHOR]

BackgroundTo examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia.MethodWithin the population-based Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI).ResultsOf the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = –1.25%, 95% confidence interval (CI) −2.05 to −0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = –1.62%, 95% CI −3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI −0.54 to 0.66).ConclusionsIn older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia. [ABSTRACT FROM AUTHOR]

BackgroundTo examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia.MethodWithin the population-based Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI).ResultsOf the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = –1.25%, 95% confidence interval (CI) −2.05 to −0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = –1.62%, 95% CI −3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI −0.54 to 0.66).ConclusionsIn older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia. [ABSTRACT FROM PUBLISHER]

. Grool AM, van der Graaf Y, Visseren FLJ, de Borst GJ, Algra A, Geerlings MI, on behalf of the SMART Study Group (University Medical Center Utrecht, Utrecht, The Netherlands). Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study. J Intern Med 2012; 272: 277-286. Objectives. Lower self-rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self-rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. Design. Patients with CAD ( n = 2547), cerebrovascular disease ( n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease ( n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self-rated health status was assessed with the Short Form-36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima-media thickness. Results. In the total population, lower self-rated physical health status (per 10-point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24-1.52], and all-cause (HR = 1.45, 95% CI 1.29-1.63) and vascular mortality (HR = 1.40, 95% CI 1.20-1.64). A 10-point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08-1.32), and all-cause (HR = 1.19, 95% CI 1.05-1.34) and vascular mortality (HR = 1.28, 95% CI 1.09-1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. Conclusions. Poorer self-rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease. [ABSTRACT FROM AUTHOR]

BackgroundThe ‘vascular depression’ hypothesis states that brain changes located in frontal-subcortical pathways increase vulnerability for specific depressive symptom profiles, but studies examining locations of small-vessel and degenerative changes with individual symptoms are scarce. We examined whether location and progression of white-matter lesions (WMLs), lacunar infarcts and atrophy were associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease.MethodIn 578 patients [63 (s.d.=8) years] of the Second Manifestations of ARTerial disease (SMART)-Medea study, volumes of WMLs and atrophy and visually rated infarcts were obtained with 1.5 T magnetic resonance imaging at baseline and after 3.9 (s.d.=0.4) years' follow-up. Depressive symptoms were assessed with Patient Health Questionnaire-9 at follow-up and categorized into motivational and mood symptoms.ResultsRegression analyses adjusted for age, gender, education, Mini-Mental State Examination, physical functioning, antidepressant use and vascular risk factors showed that location in mainly deep white-matter tracts and progression of WMLs were associated with symptoms of anhedonia, concentration problems, psychomotor retardation and appetite disturbance. Lacunar infarcts in deep white matter were associated with greater motivational [Incidence rate ratio (IRR) 1.7, 95% confidence interval (CI) 1.2–2.4] and mood (IRR 1.7, 95% CI 1.1–2.6) sumscores, and with symptoms of psychomotor retardation, energy loss and depressed mood; lacunar infarcts in the thalamus were associated with psychomotor retardation only. Cortical atrophy was associated with symptoms of anhedonia and appetite disturbance. Excluding patients with major depression did not materially change the results.ConclusionsOur findings suggest that disruption of frontal-subcortical pathways by small-vessel lesions leads to a symptom profile that is mainly characteristic of motivational problems, also in the absence of major depression. [ABSTRACT FROM PUBLISHER]

BackgroundThe different incidence rates of, and risk factors for, depression in different countries argue for the need to have a specific risk algorithm for each country or a supranational risk algorithm. We aimed to develop and validate a predictD-Spain risk algorithm (PSRA) for the onset of major depression and to compare the performance of the PSRA with the predictD-Europe risk algorithm (PERA) in Spanish primary care.MethodA prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multi-level logistic regression and inverse probability weighting to build the PSRA. In Spain (4574), Chile (2133) and another five European countries (5184), 11 891 non-depressed adult primary care attendees formed our at-risk population. The main outcome was DSM-IV major depression (CIDI).ResultsSix variables were patient characteristics or past events (sex, age, sex×age interaction, education, physical child abuse, and lifetime depression) and six were current status [Short Form 12 (SF-12) physical score, SF-12 mental score, dissatisfaction with unpaid work, number of serious problems in very close persons, dissatisfaction with living together at home, and taking medication for stress, anxiety or depression]. The C-index of the PSRA was 0.82 [95% confidence interval (CI) 0.79–0.84]. The Integrated Discrimination Improvement (IDI) was 0.0558 [standard error (s.e.)=0.0071, Zexp=7.88, p<0.0001] mainly due to the increase in sensitivity. Both the IDI and calibration plots showed that the PSRA functioned better than the PERA in Spain.ConclusionsThe PSRA included new variables and afforded an improved performance over the PERA for predicting the onset of major depression in Spain. However, the PERA is still the best option in other European countries. [ABSTRACT FROM PUBLISHER]

BackgroundThere are no risk models for the prediction of anxiety that may help in prevention. We aimed to develop a risk algorithm for the onset of generalized anxiety and panic syndromes.MethodFamily practice attendees were recruited between April 2003 and February 2005 and followed over 24 months in the UK, Spain, Portugal and Slovenia (Europe4 countries) and over 6 months in The Netherlands, Estonia and Chile. Our main outcome was generalized anxiety and panic syndromes as measured by the Patient Health Questionnaire. We entered 38 variables into a risk model using stepwise logistic regression in Europe4 data, corrected for over-fitting and tested it in The Netherlands, Estonia and Chile.ResultsThere were 4905 attendees in Europe4, 1094 in Estonia, 1221 in The Netherlands and 2825 in Chile. In the algorithm four variables were fixed characteristics (sex, age, lifetime depression screen, family history of psychological difficulties); three current status (Short Form 12 physical health subscale and mental health subscale scores, and unsupported difficulties in paid and/or unpaid work); one concerned country; and one time of follow-up. The overall C-index in Europe4 was 0.752 [95% confidence interval (CI) 0.724–0.780]. The effect size for difference in predicted log odds between developing and not developing anxiety was 0.972 (95% CI 0.837–1.107). The validation of predictA resulted in C-indices of 0.731 (95% CI 0.654–0.809) in Estonia, 0.811 (95% CI 0.736–0.886) in The Netherlands and 0.707 (95% CI 0.671–0.742) in Chile.ConclusionsPredictA accurately predicts the risk of anxiety syndromes. The algorithm is strikingly similar to the predictD algorithm for major depression, suggesting considerable overlap in the concepts of anxiety and depression. [ABSTRACT FROM PUBLISHER]

Background. It has been hypothesized that stressful life events are associated with changes in hypothalamic-pituitary-adrenal (HPA) axis regulation, which increases susceptibility to psychiatric disorders. We investigated the association of early and late life events with HPA axis regulation in older persons. Method. Within the Longitudinal Aging Study Amsterdam (LASA) 1055 participants (47% male), aged 63-93 years, collected saliva within 30 min after waking and late in the evening. Early and late life events were assessed during a home interview. The associations between life events and cortisol levels were examined using linear regression and analysis of covariance with adjustments for demographics, cardiovascular risk factors and depressive symptoms. Results. Within our sample, the median morning and evening cortisol levels were 15.0 nmol/l [interdecile range (10-90%): 7.4-27.0 nmol/l] and 2.8 nmol/l (10-90%: 1.5-6.3 nmol/l), respectively. Persons who reported early life events showed lower levels of natural log-transformed morning cortisol [B=-0.10, 95% confidence interval (CI) -0.17 to -0.04] and flattened diurnal variability of cortisol (B=-1.06, 95% CI -2.05 to -0.08). Those reporting two or more late life events showed higher levels of natural log-transformed morning cortisol (B=0.10, 95% CI 0.02-0.18) and higher diurnal variability (B=1.19, 95% CI 0.05-2.33). No associations were found with evening cortisol. Conclusions. The results of this large population-based study of older persons suggest a differential association of early and late life events with HPA axis regulation ; early life events were associated with a relative hypo-secretion of morning cortisol and flattened diurnal variability, while late life events were associated with elevated secretion of morning cortisol and high diurnal variability of cortisol. [ABSTRACT FROM AUTHOR]

Background/Aims: It has been hypothesized that cerebral hypoperfusion may contribute to cognitive deterioration. Patients with white matter lesions (WML) may be more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between CBF and cognitive performance and whether WML modified this relation. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57 ± 10 years, 77% male). Total CBF was measured with magnetic resonance angiography in the internal carotid arteries and basilar artery, and was expressed per 100 ml brain volume. Neuropsychological tests assessing executive functioning and memory were performed and composite scores were calculated. We used linear regression analyses, adjusted for age, sex, education and intelligence, to investigate the association between CBF and cognitive performance. Results: We found that WML modified the association between CBF and executive functioning (p for interaction <0.001); the association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML. Lower CBF was not associated with worse memory. Conclusion: Our results suggest that a combination of lower CBF and WML may impair executive functioning but not memory. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Context Depression is associated with an increased mortality risk. It is not known to what extent depression characteristics such as severity and length of exposure to depression contribute to the association with excess mortality. Objectives To investigate the association between depression severity and duration with mortality in community-living elderly. Design Two-wave prospective cohort study with 10-year follow-up of vital status. Assessment of depression at baseline and at three year follow-up (GMS-AGECAT). Cox proportional hazards analyses of mortality with depression according to severity and length of exposure, adjusted for demographic variables, physical illnesses, cognitive decline and functional disabilities. Setting and participants Randomly selected cohort of 3 746 non-demented older community-living persons in the city of Amsterdam. Main outcome measures Excess mortality of both the baseline cohort, and of non-demented subjects participating in both assessments (n = 1989). Results Both moderate (MHR 1.29, 95% CI 1.03–1.61) and severe depression (MHR 1.34, 95% CI 1.07–1.68) predicted 10-year mortality after multivariate adjustment. Chronic depression was associated with a 41% higher mortality risk in 6-year follow-up compared to subjects without depression. Conclusions Severity and chronicity of depression are associated with a higher mortality risk. In combination with other findings this is suggestive of a causal relationship and may have implications for both preventive and treatment strategies of late-life depression. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case–control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26–0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81–2.14). The interaction OR was 3.21 (95% CI: 1.53–6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41–0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46–1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.Journal of Human Hypertension (2008) 22, 774–780; doi:10.1038/jhh.2008.62; published online 19 June 2008 [ABSTRACT FROM AUTHOR]

Objective:Low B-vitamin status and high levels of serum homocysteine are found in depressed inpatients, but results of population-based studies of this association are inconclusive. We investigated whether a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are associated with depressive symptoms in elderly men.Methods:The study sample included a total of 332 men aged 70–90 years who were free from cardiovascular diseases and diabetes at baseline in 1990. Depressive symptoms were measured with the Zung Self-rating Depression Scale at baseline in 1990 and dietary factors with the crosscheck dietary history method in 1985 and 1990. Serum levels of homocysteine were obtained in 1985. Multiple linear and logistic regression analyses were performed.Results:Dietary intake of folate (−1.19, 95% CI −2.03; −0.36) and vitamin B6 (−2.09, 95% CI −2.92; −1.26) per standard deviation increase was associated with lower levels of serum homocysteine, while vitamin B12 was not associated with serum homocysteine. Intake of folate, vitamin B6, vitamin B12 and levels of serum homocysteine were not related to depressive symptoms.Conclusions:Our results do not support the hypothesis that a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are related to depression in healthy elderly men.European Journal of Clinical Nutrition (2008) 62, 939–945; doi:10.1038/sj.ejcn.1602804; published online 30 May 2007 [ABSTRACT FROM AUTHOR]

Purpose Anecdotal evidence suggests that antidepressants (ADs) may complicate glycaemic control. The objective of this longitudinal study was to investigate the influence of ADs on glycaemic control within diabetes patients. Methods From the pharmacy registry database PHARMO, we selected insulin users who did not use oral antidiabetics. The study population comprised: 133 patients with at least 12 months insulin use before and 6 months during an AD episode, including 56 patients with an additional 6 months of insulin use after the AD episode; 180 patients with 24 months insulin use without an AD episode. Glycaemic control was measured as the amount of insulin used, which was calculated intra-individually in 3-month periods. We stratified for selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Results Mean age (s.d.) of the subjects was 53.9 (19) years; 46.9% were men. Overall, the amount of insulin used did not change during or after AD use. No-AD users showed an increase of 16% in amount of insulin used over a period of 2 years ( p < 0.001). SSRI users showed a decrease of 13% in amount of insulin used during the AD episode ( p = 0.029), while no change was seen in TCA users. Notable was the large intra- and interindividual variation in amount of insulin used across all groups. Conclusions Overall, AD use did not influence glycaemic control in diabetes patients. The tendency for a difference between SSRIs and TCAs is suggestive for a pharmacologic effect of ADs rather than a general effect of depression on glycaemic control. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The association between depression and increased mortality risk in older persons may depend on the severity of the depressive disorder and gender.Aims: To investigate the association between major and mild depressive syndromes and excess mortality in community-living elderly men and women.Method: Depression (Geriatric Mental State AGECAT) was assessed in 4051 older persons, with a 6-year follow-up of community death registers. The mortality risk of neurotic and psychotic depression was calculated after adjustment for demographic variables, physical illness, cognitive decline and functional disabilities.Results: A total of 75% of men and 41% of women with psychotic depression had diet at follow-up. Psychotic depression was associated with significant excess mortality in both men and women. Neurotic depression was associated with a 1.67-fold higher mortality risk in men only.Conclusions: In the elderly, major depressive syndromes increase the risk of death in both men and women, but mild depression increases the risk of death only in men. [ABSTRACT FROM AUTHOR]

Background: Depression may be associated with cognitive decline in elderly people with impaired cognition.Aims: To investigate whether depressed elderly people with normal cognition are at increased risk of cognitive decline and Alzheimer's disease.Methods: Two independent samples of older people with normal cognition were selected from the community-based Amsterdam Study of the Elderly (AMSTEL) and the Longitudinal Aging Study Amsterdam (LASA). In AMSTEL, depression was assessed by means of the Geriatric Mental State Schedule. Clinical diagnoses of incident Alzheimer's disease were made using a two-step procedure. In LASA, depression was assessed with the Center for Epidemiologic Studies Depression Scale. Cognitive decline was defined as a drop of > or = 3 on the Mini-Mental State Examination at follow-up.Results: Both in the AMSTEL and the LASA sample, depression was associated with an increased risk of Alzheimer's disease and cognitive decline, respectively, but only in subjects with higher levels of education.Conclusions: In a subgroup of more highly educated elderly people, depression may be an early manifestation of Alzheimer's disease before cognitive symptoms become apparent. [ABSTRACT FROM AUTHOR]

Background: It is still not clear whether a low level of education increases the risk of developing Alzheimer's disease (AD). Two common problems in cohort studies involving an elderly population and a two-step diagnostic procedure are the loss to follow-up without data on the presence of AD, and the fact that, in general, people with higher levels of education perform better on traditional cognitive tests, such as the Mini-Mental State Examination (MMSE). Both phenomena may lead to misclassification, resulting in a biased association between level of education and AD. This study investigated to what extent these selection mechanisms may influence this association.Methods: In the community-based Amsterdam Study of the Elderly (AMSTEL) a cohort at risk for AD was selected of 3778 people aged 65-84 years. Level of education was expressed in two categories: low (primary education or less) versus high (partial secondary education to completed university education). At follow-up, a subsample of elderly people was selected for further diagnostic evaluation, using a memory test in addition to the MMSE. Clinical diagnoses of AD were made according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria. To examine the extent to which loss to follow-up may have affected the results, a sensitivity analysis was performed comparing two extreme possibilities. Furthermore, to examine to what extent use of the MMSE only may have affected the results, the observed odds ratio (OR) was compared with the OR based on only those AD patients who were selected for diagnostics with the MMSE alone.Results: After an average of 3.2 years, 77 people had developed AD. Multivariate logistic regression analyses indicated that a low level of education was associated with incident AD (OR adjusted for age and sex 2.09; 95% CI: 1.29-3.38). The results of the sensitivity analysis still indicated that a low level of education was associated with incident AD. Screening with only the MMSE led to a higher OR than the one observed.Conclusion: Selective attrition and use of cognitive screening tests that are associated with educational level may influence the strength of the association between a low level of education and incident AD; however, it appears that these influences cannot completely explain this association. [ABSTRACT FROM AUTHOR]

Background: Population studies indicate that subjective memory complaints by elderly people are correlated with cognitive performance. These complaints have some predictive power regarding the development of dementia. The present study attempted to replicate this finding, and investigated which variables determine subjective memory complaints.Method: Participants in the Amsterdam Study of the Elderly (n = 2114; 65-84 years of age), who were not demented and had a normal MMSE score (> 23) at baseline, were re-examined after four years. Subjective complaints were measured using a previously developed scale. Dementia and depression were measured using the Geriatric Mental State Schedule (GMS). Premorbid intelligence was measured by the Dutch Adult Reading Test (DART).Results: Memory complaints at baseline contributed a small but significant amount of diagnostic information with respect to the prediction of future dementia. Depressive symptoms at baseline had no predictive value when these memory complaints were accounted for. Subjective memory complaints were associated with depression, baseline MMSE score, and premorbid intelligence.Conclusions: Subjective memory complaints are not just secondary to depression, but in part reflect realistic self-observations of cognitive decline. [ABSTRACT FROM AUTHOR]