Prevalence, Clinical Management, and Natural Course of Incidental Findings on Brain MR Images: The Population-based Rotterdam Scan Study.

Purpose To present an updated prevalence estimate for incidental findings on brain magnetic resonance (MR) images and provide information on clinical relevance, including natural course, over a period of up to 9 years. Materials and Methods This study was approved by the institutional review board and all participants gave informed consent. In a prospective population-based setting, structural brain MR imaging was performed in 5800 participants (mean age, 64.9 years; 3194 women [55.1%]). Trained reviewers recorded abnormalities, which were subsequently evaluated by neuroradiologists. The prevalence with 95% confidence interval (CI) of incidental findings was determined, and clinical management of findings that required the attention of a medical specialist was followed. Follow-up imaging in the study context provided information on the natural course of findings that were not referred. Results In 549 of 5800 participants (9.5% [95% CI: 8.7%, 10.3%]), incidental findings were found, of which meningiomas (143 of 5800; 2.5% [95% CI: 2.1%, 2.9%]) and cerebral aneurysms (134 of 5800; 2.3% [95% CI: 2.0%, 2.7%]) were most common. A total of 188 participants were referred to medical specialists for incidental findings (3.2% [95% CI: 2.8%, 3.7%]). Of these, 144 (76.6% [95% CI: 70.1%, 82.1%]) either underwent a wait-and-see policy or were discharged after the initial clinical visit. The majority of meningiomas and virtually all aneurysms not referred or referred but untreated remained stable in size during follow-up. Conclusion Incidental findings at brain MR imaging that necessitate further diagnostic evaluation occur in over 3% of the general middle-aged and elderly population, but are mostly without direct clinical consequences. © RSNA, 2016.

Surgical outcomes of the Baerveldt Glaucoma Implant: differences between surgical techniques in the Rotterdam Eye Hospital.

PURPOSE: During the last decades, the Baerveldt Glaucoma Implant (BGI) has proven effective in the surgical treatment of glaucoma. Various surgical procedures have been used for its implantation and these may yield different clinical outcomes and different intraoperative and postoperative complications. We evaluated the success rate of BGI and compared complications between 2 different surgical implantation techniques. METHODS: Retrospective analyses of medical records of consecutive adult patients who underwent a BGI implantation at the Rotterdam Eye Hospital between September 2007 and August 2008. Patients were divided by the surgical implantation technique. Success was defined as an intraocular pressure ≥6 mm Hg and ≤21 mm Hg as well as a reduction of ≥20% from preoperative values. Other outcome measures were intraoperative and postoperative complications and surgical revisions of the BGI. RESULTS: A total of 173 BGI procedures were performed during the study period. Only first-ever BGI implantations in adult patients were analyzed, yielding 141 implants for the analyses. The length of follow-up averaged 11.5 months (range, 0.3 to 24.7 mo) and the mean (SD) preoperative intraocular pressure was 25.6 (8.6). Overall success rates were 75% and 83%, respectively, for the 2 different groups (P=0.40 for differences between groups). Nine patients (6%) needed a reoperation, whereas complications were documented in another 9 patients without significant differences between groups. CONCLUSIONS: Overall complication rates of the BGI were low and they combined with high success rates. Outcomes did not differ between the various surgical techniques. The choice of a certain technique might therefore be based on differences in costs and length of surgery between these techniques.

Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study.

BACKGROUND AND PURPOSE: Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease. METHODS: Overall, 1460 participants (mean age, 58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis, we obtained white matter lesion volumes. Infarcts and microbleeds were rated visually. We used linear and logistic regression models to associate aPWV with small vessel disease, adjusting for age, sex, mean arterial pressure, and heart rate and additionally for cardiovascular risk factors. Subsequently, we explored associations in strata of hypertension. RESULTS: In the study group, higher aPWV was associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.07; 95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with uncontrolled hypertension, higher aPWV was significantly associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.09; 95% CI, 0.00-0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16-3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98-2.70). No such associations were present in persons with controlled hypertension or without hypertension. CONCLUSIONS: In our study, increased arterial stiffness is associated with a larger volume of white matter lesions.

Assessment of cerebral small vessel disease predicts individual stroke risk.

BACKGROUND: Despite several known risk factors it is still difficult to foresee who will develop a stroke and who will not. Vascular brain damage, visualised with MRI, reflects how the brain tolerates the effects of vascular risk factors and may therefore be relevant in predicting individual stroke risk. OBJECTIVE: To examine whether the presence of small vessel disease on brain MRI could improve the prediction of stroke beyond the classic stroke risk factors from the 1991 Framingham Stroke Risk Function. METHODS: 1007 community-dwelling elderly people, free of stroke at baseline were included in the study. Small vessel disease--that is, the presence of silent brain infarcts (SBI) and white matter lesions (WML), was scored on MRI scans obtained in 1995-6. 10-Year stroke risk prediction was assessed by the C statistic and by reclassification adding SBI and WML to a risk model including the classic stroke risk factors. RESULTS: During 10-years of follow-up 99 strokes occurred. Individual stroke risk prediction significantly improved from 0.73 (95% CI 0.67 to 0.78) to 0.75 (0.69 to 0.80) in men and from 0.69 (0.64 to 0.75) to 0.77 (0.71 to 0.82) in women after inclusion of SBI and periventricular WML to the stroke risk factors. Reclassification occurred mainly in the intermediate stroke risk group (men 26%; women 61% reclassified). CONCLUSIONS: Assessment of small vessel disease with MRI beyond the classic stroke risk factors improved the prediction of subsequent stroke, especially in women with an intermediate stroke risk. These findings support the use of MRI as a possible tool for better identifying people at high risk of stroke.

Serum lipid levels and the risk of intracerebral hemorrhage: the Rotterdam Study.

OBJECTIVE: Low serum total cholesterol levels are associated with an increased risk of symptomatic intracerebral hemorrhage and with presence of asymptomatic cerebral microbleeds. The relative contribution of lipid fractions to these associations is unclear and requires investigation. We determined whether serum HDL-cholesterol, LDL-cholesterol, and triglycerides are associated with risk of intracerebral hemorrhage and presence of cerebral microbleeds. METHODS AND RESULTS: Nine thousand sixty-eight stroke-free community-dwelling persons aged ≥55 were followed from baseline (1990-2001) up to January 1, 2009, of whom 85 suffered from intracerebral hemorrhage during follow-up. Brain MRI was carried out in 789 healthy participants, of whom 162 had cerebral microbleeds. Triglycerides were strongly and inversely associated with intracerebral hemorrhage, independently of HDL-cholesterol, LDL-cholesterol, and potential confounders [hazard ratio for highest versus lowest quartile: 0.20 (0.06-0.69)]. Triglycerides were also associated with deep or infratentorial microbleeds [odds ratio for highest versus lowest quartile: 0.37 (0.14-0.96)], but not with strictly lobar microbleeds. No associations were found for HDL-cholesterol or LDL-cholesterol. CONCLUSIONS: Low serum triglyceride levels were associated with an increased risk of intracerebral hemorrhage and with the presence of deep or infratentorial cerebral microbleeds. This provides novel insights into the role of lipid fractions, particularly triglycerides, in the etiology of intracerebral hemorrhage.

Incidental findings on brain Magnetic Resonance Imaging in long-term survivors of breast cancer treated with adjuvant chemotherapy.

PURPOSE: Incidental brain findings defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered at brain imaging and are unrelated to the purpose of the examination are common in the general population. Because it is unclear whether the prevalence of incidental findings in breast cancer patients treated with chemotherapy is different to that in the general population, we compared the prevalence in breast cancer survivors treated with chemotherapy to that in a population-based sample of women without a history of any cancer. PATIENTS AND METHODS: Structural brain MRI (1.5T) was performed in 191 female CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) chemotherapy-exposed breast cancer survivors. A reference group of 1590 women without a history of cancer was sampled from a population-based cohort study. All participants were aged 50 to 80 years. Five trained reviewers recorded the brain abnormalities. Two experienced neuro-radiologists reviewed the incidental findings. RESULTS: The cancer survivors had completed chemotherapy on average 21 years before. Of the 191 subjects, 2.6% had an aneurysm and 3.7% had a meningioma. The prevalence of meningiomas and aneurysms was not different between the groups. The prevalence of pituitary macro adenomas in the breast cancer survivors (1.6%) was higher than that in the reference group (0.1%) (OR=23.7; 95% CI 2.3-245.8). CONCLUSION: Contrary to commonly held opinions, we did not observe an increased prevalence of meningiomas in cancer survivors. Breast cancer survivors previously treated with chemotherapy are more likely to develop pituitary adenomas than persons without a history of cancer and chemotherapy treatment.

Lobar distribution of cerebral microbleeds: the Rotterdam Scan Study.

OBJECTIVE: To investigate the distribution of lobar microbleeds over the different lobes, taking into account lobar volume and clustering effects of multiple microbleeds. DESIGN: Population-based, cross-sectional analysis. SETTING: The Rotterdam Scan Study. PARTICIPANTS: A total of 198 persons (age range, 61-95 years) with lobar microbleeds. MAIN OUTCOME MEASURES: Distribution of microbleeds over different lobes. RESULTS: We found that lobar cerebral microbleeds occurred significantly more often in the temporal lobe, a region known to be more affected in cerebral amyloid angiopathy. CONCLUSION: This study corroborates the presumed association of lobar microbleeds with cerebral amyloid angiopathy.

Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study.

BACKGROUND AND PURPOSE: Cerebral microbleeds are frequently seen in the general elderly population, but it is unknown at what rate they occur with aging and whether once present can disappear over time. METHODS: As part of the Rotterdam Scan Study, 831 persons (mean age, 68.5 years) underwent repeated brain MRI with a mean interval of 3.4 years. We assessed determinants of incident microbleeds in relation to their location with multiple logistic regressions. RESULTS: Overall prevalence of microbleeds increased from 24.4% at baseline to 28.0% at follow-up. Eighty-five persons (10.2%) developed new microbleeds. Microbleeds at baseline predicted development of new microbleeds (OR, 5.38; 95% CI, 3.34 to 8.67). In only 6 persons with microbleeds at baseline, fewer microbleeds were present at the follow-up examination. Cardiovascular risk factors, presence of lacunar infarcts, and larger white matter lesion volume at baseline were all associated with incident deep or infratentorial microbleeds, whereas people with the apolipoprotein E ε4/ε4 genotype or larger white matter lesion volume had a higher risk of incident strictly lobar microbleeds. CONCLUSIONS: Incidence of microbleeds in the general population over a 3-year interval was substantial and microbleeds rarely disappeared. Risk factors for incident microbleeds were similar to those for prevalent microbleeds and differed according to microbleed location. These results support the assessment of microbleeds on T2-weighted MRI as a possible marker of both cerebral amyloid angiopathy and hypertensive vasculopathy progression.

Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study.

BACKGROUND AND PURPOSE: We previously reported on the high prevalence of cerebral microbleeds (CMBs) in community-dwelling people aged 60 years and older. Moreover, we found that their spatial distribution likely reflects differences in underlying etiology. We have since almost quadrupled the number of participants in our study and expanded it to include persons of 45 years and older. We examined the prevalence and determinants of microbleeds in this larger and younger cohort from the general population. METHODS: In 3979 persons (mean age, 60.3 years), we performed brain MRI at 1.5T, including a sequence optimized for visualization of CMBs. Associations between APOE genotype, cardiovascular risk factors, and markers of cerebrovascular disease with the presence and location of CMBs were assessed by multiple logistic regression adjusted for age, sex, and relevant confounders. RESULTS: Microbleed prevalence gradually increased with age, from 6.5% in persons aged 45 to 50 years to 35.7% in participants of 80 years and older. Overall, 15.3% of all subjects had at least 1 CMB. Cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial region, whereas APOE ε4 and diastolic blood pressure were related to microbleeds in a strictly lobar location. CONCLUSIONS: Findings in this larger population are in line with our previous results and, more importantly, extend these to a younger age group. CMBs are already present at middle age, and prevalence rises strongly with increasing age. We confirmed that determinants of the presence of cerebral microbleeds differ according to their location in the brain.

Total cerebral blood flow in relation to cognitive function: the Rotterdam Scan Study.

Cerebral hypoperfusion has been associated with worse cognitive function. We investigated the association between cerebral blood flow and cognition and whether this association is independent of brain volume. In 892 participants, aged 60 to 91 years, of the population-based Rotterdam Scan study, we measured total cerebral blood flow (tCBF) and brain volume using magnetic resonance imaging. Lower tCBF was associated with worse information-processing speed, executive function, and global cognition. However, after correcting tCBF for brain volume, these associations disappeared. The association between tCBF and cognition may be mediated or confounded by brain atrophy. Future studies on tCBF should take into account brain atrophy.

Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study.

BACKGROUND AND PURPOSE: Arterial stiffness is associated with an increased risk of myocardial infarction and stroke, independent of classical vascular risk factors. Vascular factors and stroke are associated with cognitive function and dementia. We examined whether arterial stiffness was independently associated with cognitive function and dementia. METHODS: The present study was based on the Rotterdam Study, a prospective population-based cohort study ongoing since 1990. During the third examination (1997-1999) arterial stiffness was measured by assessment of pulse wave velocity and carotid distensibility. Cognitive function was assessed during the third and fourth examination (2002-2004) with a neuropsychological test battery. We used linear and logistic regression to estimate the association of arterial stiffness with cognitive function and cognitive decline. From the third examination until January 1, 2005, we identified 156 incident dementia cases. Cox proportional hazard models were used to estimate the association between arterial stiffness and the risk of dementia. RESULTS: After adjustment for cardiovascular risk factors we found an association of increased pulse wave velocity with poorer performance on the Stroop test (adjusted beta-coefficient [95% confidence interval] 1.13 [0.26 to 1.99] per standard deviation increase in pulse wave velocity) but not with performance on other cognitive tests. No associations were found between measures of arterial stiffness and cognitive decline or risk of dementia after adjustment for cardiovascular factors. CONCLUSIONS: We did not identify arterial stiffness as an independent risk factor of cognitive decline or risk of dementia.