Professional occupation and the risk of Parkinson's disease.

BACKGROUND AND PURPOSE: Creativity in Parkinson's disease (PD) is strongly related to dopaminergic activity and medication. We hypothesized that patients with PD, including those who are in the pre-diagnostic phase of PD, are prone to choose highly structured 'conventional' professional occupations and avoid highly creative 'artistic' occupations. METHODS: At baseline of the population-based Rotterdam Study, we asked 12 147 individuals aged ≥45 years about their latest occupation and categorized occupations according to the RIASEC model. Participants underwent baseline and follow-up (median 11 years) examinations for PD. We determined associations of artistic (versus any other occupation) and conventional (versus any other occupation) occupations with PD. Additionally, we pooled our results with a recently published case-control study (Radboud Study). RESULTS: At baseline, conventional occupations were common [n = 4356 (36%)], whereas artistic occupations were rare [n = 137 (1%)]. There were 217 patients with PD, including 91 with prevalent PD and 126 with incident PD. The risk of PD varied substantially across occupational categories (chi-square, 14.61; P = 0.01). The penalized odds ratio (OR) of artistic occupations for PD was 0.19 [95% confidence interval (CI), 0.00-1.31; P = 0.11], whereas the OR of conventional occupations for PD was 1.23 (95% CI, 0.95-1.66; P = 0.10). The direction and magnitude of ORs were similar in cross-sectional and longitudinal subsamples. Pooled ORs across the Rotterdam and Radboud Studies were 0.20 (95% CI, 0.08-0.52; P < 0.001) for artistic and 1.23 (95% CI, 0.92-1.67; P = 0.08) for conventional occupations. CONCLUSIONS: The risk of PD varies substantially by choice of professional occupation. Our findings suggest that dopaminergic degeneration affects choice of occupation, which may start in the pre-diagnostic phase of PD.

Glucose in prediabetic and diabetic range and outcome after stroke.

OBJECTIVES: Newly diagnosed disturbed glucose metabolism is highly prevalent in patients with stroke. Limited data are available on their prognostic value on outcome after stroke. We aimed to assess the association of glucose in the prediabetic and diabetic range with unfavourable short-term outcome after stroke. MATERIALS AND METHODS: We included 839 consecutive patients with ischemic stroke and 168 patients with intracerebral haemorrhage. In all nondiabetic patients, fasting glucose levels were determined on day 2-4. Prediabetic range was defined as fasting glucose of 5.6-6.9 mmol/L, diabetic range as ≥7.0 mmol/L, pre-existent diabetes as the use of anti-diabetic medication prior to admission. Outcome measures were poor functional outcome or death defined as modified Rankin Scale (mRS) score >2 and discharge not to home. The association of prediabetic range, diabetic range and pre-existent diabetes (versus normal glucose) with unfavourable outcome was expressed as odds ratios, estimated with multiple logistic regression, with adjustment for prognostic factors. RESULTS: Compared with normal glucose, prediabetic range (aOR 1.8; 95%CI 1.1-2.8), diabetic range (aOR 2.5; 95%CI 1.3-4.9) and pre-existent diabetes (aOR 2.6; 95%CI 1.6-4.0) were associated with poor functional outcome or death. Patients in the prediabetic range (aOR 0.6; 95%CI 0.4-0.9), diabetic range (aOR 0.4; 95%CI 0.2-0.9) and pre-existent diabetes (aOR 0.6; 95%CI 0.4-0.9) were more likely not to be discharged to home. CONCLUSIONS: Patients with glucose in the prediabetic and diabetic range have an increased risk of unfavourable short-term outcome after stroke. These findings illustrate the potential impact of early detection and treatment of these patients.

N-terminal pro-B-type natriuretic peptide and the risk of stroke and transient ischaemic attack: the Rotterdam Study.

BACKGROUND AND PURPOSE: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population-based Rotterdam Study, the association of NT-proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated. METHODS: NT-proBNP was measured in 1997-2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex. RESULTS: During 22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person-years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29-1.76] and in women (HR 1.24; 95% CI 1.05-1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26-1.82) but not in men (HR 1.02; 95% CI 0.83-1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow-up did not change the associations. CONCLUSIONS: Higher NT-proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.

Is isolated aphasia a typical presentation of presumed cardioembolic transient ischemic attack or stroke?

BACKGROUND: Previous studies have suggested that patients with a transient ischemic attack (TIA) or minor ischemic stroke and isolated aphasia should be carefully screened for a potential cardiac source of embolism. Most of these publications, however, were case reports or small-series. The purpose of this study was to assess the relationship between isolated aphasia and atrial fibrillation (AF) as the cause of presumed cardioembolic TIA or stroke within the setting of 2 large multicenter trials. METHODS: The frequency of isolated aphasia was compared between patients with a TIA or minor ischemic stroke either with AF [European Atrial Fibrillation Trial (EAFT), n = 1,001] or without AF [Dutch TIA Trial (DTT), n = 3,150]. We analyzed data with univariable and multivariable logistic regression. Isolated aphasia was defined as aphasia without dysarthria, visual-field defects or motor or sensory deficits of the arm, leg or face. Because dysarthria can be difficult to detect in aphasic patients, a second analysis was done without excluding dysarthric patients. In a third analysis, we excluded patients with a symptomatic lacunar infarct from the DTT, as these patients were overrepresented due to the exclusion of patients with AF. Subgroup analysis was performed for patients presenting with TIA and minor stroke. RESULTS: Of 4,151 patients, 210 (5.1%) had isolated aphasia, 109 from the EAFT and 101 from the DTT, crude odds ratio (OR) 3.69, 95% confidence interval (CI) 2.79-4.89. Patients with isolated aphasia were older (mean age 70.3 vs. 66.8 years, p < 0.01), more often female (OR 1.87, 95% CI 1.41-2.46), and more often had diabetes (OR 1.73, 95% CI 1.16-2.59) and hypercholesterolemia (OR 1.83, 95% CI 1.11-3.03) than those without aphasia. After simultaneous adjustment for age, sex, diabetes and hypercholesterolemia, patients with isolated aphasia still had AF more often than patients without isolated aphasia (adjusted OR 2.94, 95% CI 2.16-4.01). Both after inclusion of patients with dysarthria in the group of patients with isolated aphasia and after exclusion of patients with a symptomatic lacunar infarct, essentially the results remained the same. Patients presenting with isolated aphasia due to a TIA tended to have AF more often than patients with a minor ischemic stroke. CONCLUSIONS: Isolated aphasia is an independent sign of AF in patients with a TIA or minor ischemic stroke. Careful cardiac screening seems warranted in patients with isolated aphasia, as secondary prevention is different in patients with a cardiac source of embolism.

Structural and diffusion MRI measures of the hippocampus and memory performance.

Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in patients with Alzheimer's disease. We examined the association between hippocampal volumes, DTI measures of the hippocampus and memory performance in 892 non-demented persons (age ≥ 55 years) across different age groups. Hippocampal volume was segmented on 3D volumetric MRI scans. The segmentations were co-registered to mean diffusivity (MD) and fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements. Higher MD of the hippocampus was associated with impaired verbal memory performance. In all persons ≥ 55 years, a higher MD of the hippocampus was associated with a worse memory performance. Hippocampal volumes were very weakly positively associated with delayed recall and only in persons > 65 years. FA of the hippocampus was not associated with memory performance. Follow-up studies will be needed to determine whether higher MD of hippocampus at younger ages could be an earlier marker of incident Alzheimer's disease than hippocampal volume.

Tiotropium Handihaler and the risk of cardio- or cerebrovascular events and mortality in patients with COPD.

BACKGROUND: Tiotropium has been associated with an increased risk of mortality and/or cardiovascular events. Recent data from RCTs suggests tiotropium Handihaler to be safe, but its safety has not yet been fully investigated under real-life circumstances. METHODS: We conducted 2 nested case-control studies in a COPD cohort from the Dutch IPCI database. In the first case-control study, cases had a cardiovascular or cerebrovascular endpoint (CCVE): stroke and transient ischemic attack (TIA), myocardial infarction, heart failure and/or ventricular arrhythmia. In the second, cases were all patients who died. Cases were matched to controls on age, sex and index date. Conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (CI) for tiotropium vs. long-acting beta-agonists (LABA). RESULTS: Within a cohort of 6788 COPD patients, 784 CCVE's and 1032 deaths were reported. Compared to current LABA use, use of tiotropium Handihaler was neither associated with an increased risk of a CCVE (OR(adj) 0.89, 95% 0.55-1.44) nor with an increased risk of death (OR(adj) 0.79, 95% CI 0.49-1.28). CONCLUSIONS: In real life, use of tiotropium Handihaler in COPD patients is not associated with an increased risk of a CCVE or mortality compared to LABA.

Effects of high-dose paracetamol on blood pressure in acute stroke.

BACKGROUND: Early administration of paracetamol may improve outcome of patients with acute stroke and a baseline body temperature of 37°C or above by lowering body temperature and preventing fever. Besides its antipyretic effects, paracetamol may affect blood pressure through cyclooxygenase-2 inhibition. We therefore aimed to assess the effect of high-dose paracetamol on blood pressure in patients with acute stroke. METHODS: We analyzed data of 540 patients admitted within 24 h of stroke onset who were randomized to treatment with either paracetamol (6 g daily) or placebo. Blood pressures were measured at 12, 24, and 48 h from the start of treatment. Changes in blood pressure from baseline in the two treatment groups and corresponding 95% confidence intervals (CI) were calculated with linear regression analysis. Adjustments for potential confounders were made with a multiple linear regression model. RESULTS: Treatment with high-dose paracetamol was associated with a significant reduction in systolic blood pressure of 4.5 mm Hg (95% CI 0.6-8.5) at 12 h from the start of treatment. This effect was no longer present after 24 and 48 h. CONCLUSION: High-dose paracetamol reduces not only body temperature but also systolic blood pressure in the first 12 h after start of treatment. Both effects may improve functional outcome after stroke, but this needs further study.

Efficacy of early cognitive-linguistic treatment and communicative treatment in aphasia after stroke: a randomised controlled trial (RATS-2).

BACKGROUND: The two main approaches in aphasia treatment are cognitive-linguistic treatment (CLT), aimed at restoring the linguistic levels affected, semantics, phonology or syntax, and communicative treatment, aimed at optimising information transfer by training compensatory strategies and use of residual language skills. The hypothesis that CLT is more effective than communicative treatment in the early stages after stroke was tested in this study. METHODS: In this multicentre, randomised, parallel group trial with blinded outcome assessment, 80 patients with aphasia after stroke were included within 3 weeks post-stroke. Patients received 6 months of CLT, comprising semantic and/or phonological training, or communicative treatment for at least 2 h per week. They were assessed before treatment and at 3 and 6 months with the Amsterdam-Nijmegen Everyday Language Test (ANELT-A, primary outcome) and semantic and phonological tests (secondary outcomes). The intervention effect was evaluated by means of analysis of covariance, with adjustment for baseline scores. RESULTS: There was no difference between the mean ANELT-A score of the CLT group (n=38) and the communicative treatment group (n=42), at 3 months (adjusted difference 1.5, 95% CI -2.6 to 5.6) or at 6 months (adjusted difference 1.6, 95% CI -2.3 to 5.6) post-stroke. On two of six specific semantic and phonological tests, the mean scores differed significantly, both in favour of CLT. CONCLUSION: This study does not confirm the hypothesis that patients with aphasia after stroke benefit more from CLT, aimed at activation of the underlying semantic and phonologic processes, than from general, non-specific communicative treatment (ISRCTN67723958 Current Controlled Trials).

The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.

BACKGROUND - Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI-MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. METHODS - Five hundred and ninety-eight consecutive patients underwent TCD investigation. Outcome events were fatal or non-fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. RESULTS - TCD registration was successful in 489 patients. Mean follow-up was 2.1 years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3-6.0) and major vascular events (HR 2.6; 95% CI: 1.3-5.0). Each unit increase in PI-MFV ratio was associated with a HR 2.8 (95% CI: 1.7-4.8) for stroke and HR 2.2 (95% CI: 1.3-3.6) for major vascular events. CONCLUSION - In patients with a TIA or non-disabling ischemic stroke, MFV and the PI-MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.

BACKGROUND AND PURPOSE: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. MATERIALS AND METHODS: We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. RESULTS: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). CONCLUSIONS: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Heart failure and the risk of stroke: the Rotterdam Study.

Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (1990­1993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.15­15.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.96­6.25] after 1­6 months and 0.83 [95% CI 0.53­1.29] after 0.5­6 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure.

Cognitive and physical impairment and the risk of stroke - A prospective cohort study.

The manifestation of cognitive and physical impairment in stroke patients before the acute event suggests accumulating subclinical vascular pathology in the brain. We investigated whether impairments in cognitive and physical functioning were associated with an increased stroke risk. Between 2002 and 2008, 8,519 stroke-free non-demented participants from the population-based Rotterdam Study underwent cognition and physical assessments including Mini-Mental State Examination, 15-word learning test, Stroop test, letter-digit substitution test, verbal fluency test, Purdue pegboard test and questionnaires on basic and instrumental activities of daily living (BADL; IADL). Principal component analysis was used to derive global cognition (G-factor). Incident stroke was assessed through continuous monitoring of medical records until 2016. Among 8,519 persons (mean age 66.0 years; 57.8% women), 489 suffered a stroke during mean follow-up of 8.7 years (SD: 2.9). Worse G-factor was associated with higher stroke risk (Hazard Ratio 1.21, 95% CI: 1.06-1.38), largely driven by unspecified stroke. Likewise, worse scores on 15-word learning test, Stroop test, Purdue pegboard test, IADL, and BADL were associated with higher risk of stroke. Thus both worse cognitive and physical functioning were associated with a higher stroke risk, in particular unspecified stroke and persons with worse memory, information processing, executive function, and motor function.

Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study.

BACKGROUND: Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease (AD). Prospective studies have provided inconsistent evidence. Moreover, it is unclear whether the association differs for lipophilic statins, those that could more easily pass the blood-brain barrier and hydrophilic statins. OBJECTIVES: To prospectively evaluate whether use of statins is associated with the risk of AD, and to determine whether associations differ for lipophilic and hydrophilic statins. METHOD: 6992 participants of the prospective, population-based Rotterdam Study were followed, from baseline (1990-1993) until January 2005 for incident AD. Data on all filled prescriptions came from pharmacy records. For each date on which each event occurred, cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as "any" or "never" use. A distinction was made between statin, lipophilic and hydrophilic statins, and non-statin cholesterol-lowering drugs. Data were analysed with the Cox regression analysis, adjusting for sex, age and potential confounders. RESULTS: During follow-up (mean 9 years), 582 persons developed AD. Compared with never use of cholesterol-lowering drugs, statin use was associated with a decreased risk of AD (HR 0.57; 95% CI 0.37 to 0.90), but non-statin cholesterol-lowering drug use was not (HR 1.05; 95% CI 0.45 to 2.44). HRs were equal for lipophilic (HR 0.54; 95% CI 0.32 to 0.89) and hydrophilic statins (HR 0.54; 95% CI 0.26 to 1.11). CONCLUSION: In the general population, the use of statins, but not of non-statin cholesterol-lowering drugs, was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs. The protective effect was independent of the lipophilicity of statins.

Risk indicators for development of headache during dipyridamole treatment after cerebral ischaemia of arterial origin.

A considerable proportion of patients discontinue dipyridamole therapy because of headache. Risk indicators for the development of dipyridamole induced headache were identified by means of an exploratory analysis of data from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) and the Second European Stroke Prevention Study (ESPS 2). In ESPRIT, dipyridamole induced headache was significantly associated with female sex, absence of hypertension and non-smoking (area under the receiver operator characteristic (ROC) curve 0.63 (95% CI 0.58 to 0.68)) and in ESPS 2 with female sex and absence of ischaemic lesions on imaging (area under the ROC curve 0.64 (95% CI 0.59 to 0.69)).

Impact of early surgery after aneurysmal subarachnoid haemorrhage.

OBJECTIVES: To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989-1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996-1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. RESULTS: Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0-39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1-99.4). CONCLUSIONS: Our results support the widely adopted practice of ES in good-grade SAH patients.

Association between fibrinogen and fibrinogen γ' and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study.

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025.

Depressive symptoms and risk of stroke: the Rotterdam Study.

BACKGROUND: Previous studies that have assessed whether the presence of depressive symptoms predisposes to stroke in the general elderly population have been contradictory. Moreover, they did not distinguish between men and women and did not perform psychiatric workups in those with depressive symptoms. This study examines the association between depressive symptoms, depressive disorder and the risk of stroke in the general population. METHODS: This prospective population based cohort study included 4424 participants from the third Rotterdam Study Survey (1997-1999) who, at that time, were > or =61 years of age and free from stroke. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale (CESD) and considered present if the CESD score was > or =16. Participants with depressive symptoms had a diagnostic interview for depressive disorder. Follow-up was complete until 1 January 2005. Data were analysed using Cox proportional hazards models with adjustment for relevant confounders. RESULTS: Men with depressive symptoms (n = 73) were at increased risk of stroke (adjusted hazard ratio (HR) 2.17; 95% CI 1.11 to 4.23) and ischaemic stroke (adjusted HR 3.21; 95% CI 1.62 to 6.38). These associations were at least partly attributable to men who reported depressive symptoms but who did not fulfil Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic criteria for depressive disorder (n = 32): they had a very high risk of stroke (adjusted HR 2.70; 95% CI 1.15 to 6.33) and ischaemic stroke (adjusted HR 4.01; 95% CI 1.68 to 9.57). In women there was no association between presence of depressive symptoms and risk of stroke. CONCLUSIONS: Presence of depressive symptoms is a strong risk factor for stroke in men but not in women.