Higher education is associated with a lower risk of dementia after a stroke or TIA

__Background:__ Higher education is associated with a lower risk of dementia, possibly because of a higher tolerance to subclinical neurodegenerative pathology. Whether higher education also protects against dementia after clinical stroke or transient ischemic attack (TIA) remains unknown. __Methods:__ Within the population-based Rotterdam Study, 12,561 participants free of stroke, TIA and dementia were followed for occurrence of stroke, TIA and dementia. Across the levels of education, associations of incident stroke or TIA with subsequent development of dementia and differences in cognitive decline following stroke or TIA were investigated. __Results:__ During 124,862 person-years, 1,463 persons suffered a stroke or TIA, 1,158 persons developed dementia, of whom 186 developed dementia after stroke or TIA. Risk of dementia after a stroke or TIA, compared to no stroke or TIA, was highest in the low education category (hazards ratio [HR] 1.46, 95% CI 1.18-1.81) followed by intermediate education category (HR 1.36, 95% CI 1.03-1.81). No significant association was observed in the high education category (HR 0.62, 95% CI 0.25-1.54). In gender stratified analyses, decrease in risk of dementia with increasing education was significant only in men. __Conclusion:__ Higher education is associated with a lower risk of dementia after stroke or TIA, particularly in men, which might be explained by a higher cognitive reserve

The potential for prevention of dementia across two decades: The prospective, population-based Rotterdam Study

Background: Cardiovascular factors and low education are important risk factors of dementia. We provide contemporary estimates of the proportion of dementia cases that could be prevented if modifiable risk factors were eliminated, i.e., population attributable risk (PAR). Furthermore, we studied whether the PAR has changed across the last two decades. Methods: We included 7,003 participants of the original cohort (starting in 1990) and 2,953 participants of the extended cohort (starting in 2000) of the Rotterdam Study. Both cohorts were followed for dementia until ten years after baseline. We calculated the PAR of overweight, hypertension, diabetes mellitus, cholesterol, smoking, and education. Additionally, we assessed the PAR of stroke, coronary heart disease, heart failure, and atrial fibrillation. We calculated the PAR for each risk factor separately and the combined PAR taking into account the interaction of risk factors. Results: During 57,996 person-years, 624 participants of the original cohort developed dementia, and during 26,177 person-years, 145 participants of the extended cohort developed dementia. The combined PAR in the original cohort was 0.23 (95 % CI, 0.05-0.62). The PAR in the extended cohort was slightly higher at 0.30 (95 % CI, 0.06-0.76). The combined PAR including cardiovascular diseases was 0.25 (95 % CI, 0.07-0.62) in the original cohort and 0.33 (95 % CI, 0.07-0.77) in the extended cohort. Conclusions: A substantial part of dementia cases could be prevented if modifiable risk factors would be eliminated. Although prevention and treatment options of cardiovascular risk factors and diseases have improved, the preventive potential for dementia has not declined over the last two decades

Unspecified Strokes: Time Trends, Determinants, and Long-Term Prognosis in the General Population

Introduction: In the absence of neuroimaging, a stroke is typically labelled as unspecified. While the majority of clinic-based stroke research focuses on hemorrhagic or ischemic stroke, in the general population, a substantial proportion of strokes remains unspecified. Objective: To investigate time trends in the occurrence and determinants of unspecified strokes and differences in patient characteristics and survival compared to ischemic or hemorrhagic stroke. Methods: We included 1,546 participants from the population-based Rotterdam Study who suffered a first-ever stroke during follow-up (1990-2016). We calculated the proportion of unspecified strokes per year and compared their characteristics between 3 time periods (1990-1999, 2000-2009, and 2010-2016) using a chi-square test, and furthermore investigated differences between unspecified, ischemic, and hemorrhagic stroke in patient characteristics and survival using age- and sex-adjusted survival curves. Results: The occurrence of unspecified stroke among all strokes decreased from 75% in 1990 to 16% in 2016. Compared to the first time period (1991-1999), diagnosis of unspecified strokes was more often done by nursing home physicians (13 vs. 40%) and unspecified stroke patients had more often dementia (30 vs. 43%) in the last time period (2010-2016). Compared to patients with ischemic or hemorrhagic stroke, patients with unspecified stroke were on average older (84.3 vs. 78.5 years) and had more often physical impairments and dementia. Furthermore, patients with unspecified stroke had a lower survival probability up to 10 years after stroke than those with ischemic stroke. Conclusions: The proportion of unspecified strokes decreased drastically from 75 to 16% in the last decades. Patients who do not undergo neuroimaging and therefore are classified as unspecified stroke represent an older, more frail patient group that suffers more often from multimorbidities and poor long-term prognosis than those who do undergo neuroimaging and are thus classified as ischemic or hemorrhagic stroke

Genetic loci for serum lipid fractions and intracerebral hemorrhage

Background: Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds. Methods: Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997-2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds. Results: After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants s

Global Brain Perfusion and the Risk of Transient Ischemic Attack and Ischemic Stroke: The Rotterdam Study

Background-—The role of subtle disturbances of brain perfusion in the risk of transient ischemic attack (TIA) or ischemic stroke remains unknown. We examined the association between global brain perfusion and risk of TIA and ischemic stroke in the general population. Methods and Results-—Between 2005 and 2015, 5289 stroke-free participants (mean age, 64.3 years; 55.6% women) from the Rotterdam Study underwent phase-contrast brain magnetic resonance imaging at baseline to assess global brain perfusion. These participants were followed for incident TIA or ischemic stroke until January 1, 2016. We investigated associations between global brain perfusion (mL of blood flow/100 mL of brain/min) and risk of TIA and ischemic stroke using Cox regression models with adjustment for age, sex, and cardiovascular risk factors. Additionally, we investigated whether associations were modified by retinal vessel calibers, small and large vessel disease, blood pressure, and heart rate. During a median follow-up of 7.2 years (36 103 person-years), 137 participants suffered a TIA and another 108 an ischemic stroke. We found that lower global brain perfusion was associated with a higher risk of TIA, but not with the risk of ischemic stroke (adjusted hazard ratio, 95% CI, per standard deviation decrease of global brain perfusion: 1.29, 1.07–1.55 for TIA and adjusted hazard ratio of 1.06, 0.87–1.30 for ischemic stroke). Across strata of wider arteriolar retinal calibers, lower brain perfusion was more prominently associated with TIA, but not with ischemic stroke. Conclusions-—In a community-dwelling population, impaired global brain perfusion increased the risk of TIA, but not of ischemic stroke

Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study

Objective: To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Design: Prospective population based cohort study. Setting: People living in the community in Rotterdam, the Netherlands. Participants: 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline. Main outcome measures First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. Results: During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were −7 for any cardiovascular disease, −102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and −1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke. Conclusions: At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages

Sex differences in lifetime risk and first manifestation of cardiovascular disease: Prospective population based cohort study

Objective: To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Design: Prospective population based cohort study. Setting: People living in the community in Rotterdam, the Netherlands. Participants: 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline. Main outcome measures: First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. Results: During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1