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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]

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]

Background and Purpose: The clinical relevance of cortical microinfarcts has recently been established; however, studies on microinfarcts in the deep gray matter are lacking. We examined the risk factors and MR imaging correlates of microinfarcts in the deep gray matter on 7T MR imaging and their relation to cognitive functioning., Materials and Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, 213 patients (mean age, 68 [SD, 8] years) had a risk-factor assessment, 7T and 1.5T brain MR imaging, and a cognitive examination. Microinfarcts on 7T MR imaging were defined as lesions of <5 mm. Regression models were used to examine the age-adjusted associations among risk factors, MR imaging markers, and microinfarcts. Cognitive function was summarized as composite and domain-specific z scores., Results: A total of 47 microinfarcts were found in 28 patients (13%), most commonly in the thalamus. Older age, history of stroke, hypertension, and intima-media thickness were associated with microinfarcts. On 1.5T MR imaging, cerebellar infarcts (relative risk = 2.75; 95% CI, 1.4-5.33) and lacunes in the white (relative risk = 3.28; 95% CI, 3.28-6.04) and deep gray matter (relative risk = 3.06; 95% CI, 1.75-5.35) were associated with microinfarcts, and on 7T MR imaging cortical microinfarcts (relative risk = 2.33; 95% CI, 1.32-4.13). Microinfarcts were also associated with poorer global cognitive functioning (mean difference in the global z score between patients with multiple microinfarcts versus none = -0.97; 95% CI, -1.66 to -0.28, P = .006) and across all cognitive domains., Conclusions: Microinfarcts in the deep gray matter on 7T MR imaging were associated with worse cognitive functioning and risk factors and MR imaging markers of small-vessel and large-vessel disease. Our findings suggest that microinfarcts in the deep gray matter may represent a novel imaging marker of vascular brain injury., (© 2022 by American Journal of Neuroradiology.)

Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS. A machine learning approach identified PVS in an automatically positioned ROI in the centrum semiovale (CSO), based on -resolution T2-weighted TSE scans. Next, 3D PVS tracking was performed in 50 subjects (mean age 62.9 years (range 27-78), 19 male), and quantitative measures were extracted. Maps of PVS density, length, and tortuosity were created. Manual PVS annotations were available to train and validate the automatic method. Good correlation was found between the automatic and manual PVS count: ICC (absolute/consistency) is 0.64/0.75, and Dice similarity coefficient (DSC) is 0.61. The automatic method counts fewer PVS than the manual count, because it ignores the smallest PVS (length <2 mm). For 20 subjects manual PVS annotations of a second observer were available. Compared with the correlation between the automatic and manual PVS, higher inter-observer ICC was observed (0.85/0.88), but DSC was lower (0.49 in 4 persons). Longer PVS are observed posterior in the CSO compared with anterior in the CSO. Higher PVS tortuosity are observed in the center of the CSO compared with the periphery of the CSO. Our fully automatic method can detect PVS in a 2D slab in the CSO, and extract quantitative PVS parameters by performing 3D tracking. This method enables automated quantitative analysis of PVS., (© 2022 The Author(s).)

Objectives: Stroke is the second most common cause of death and a major cause of disability. Besides the physical consequences, depressive symptoms are frequent in the aftermath after stroke. Every year, approximately 15 million stroke survivors worldwide are at risk of developing post-stroke depression. In this study we describe the natural course of depressive symptoms in stroke patients over a long-period of time post stroke and identify associated determinants., Materials and Methods: From the Second Manifestations of ARTerial disease-Memory, depression and aging (SMART-Medea) study, an observational prospective cohort study, we selected patients with cerebrovascular disease, and used the biannually collected data of the Patient Health Questionnaire-9 for depressive symptoms. A score of ≥10 indicated the presence of depressive symptoms. A multinomial logistic regression analysis was used to identify prognostic determinants for courses of depressive symptoms after stroke., Results: During a mean follow-up time of 7.9 years, 62% of the 172 participants was never depressed, 19% had a single episode and 19% had recurrent depressive symptoms. Physical function was associated with increased risk for single episode and recurrent depressive symptoms (OR=1.06 [1.01-1.11]). OR's for social, mental and (vascular) comorbidities variables were not significant. Participants' physical function was only measured at baseline. Several relevant variables were not present in this dataset, including information about clinical events during follow-up., Conclusion: Nearly 40% of the participants are confronted with depressive symptoms on the long-term. Physical function plays a substantial part for stroke survivors in the development of these symptoms., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Intracranial atherosclerosis, a major risk factor for ischemic stroke, is thought to have different atherogenic mechanisms than extracranial atherosclerosis. Studies investigating their relationship in vivo are sparse and report inconsistent results. We studied the relationship between intracranial atherosclerosis and extracranial atherosclerosis in a cohort of patients with a history of vascular disease., Materials and Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART) study, cross-sectional analyses were performed in 130 patients (mean age, 68 ± 9 years) with a history of vascular disease and with assessable 7T intracranial vessel wall MR imaging data. Intracranial atherosclerosis burden was defined as the number of intracranial vessel wall lesions in the circle of Willis and its major branches. Age- and sex-adjusted unstandardized regression coefficients ( b -value) were calculated with intracranial atherosclerosis burden as the dependent variable and extracranial atherosclerosis markers as independent variables., Results: Ninety-six percent of patients had ≥1 vessel wall lesion, with a mean intracranial atherosclerosis burden of 8.5 ± 5.7 lesions. Significant associations were observed between higher intracranial atherosclerosis burden and carotid intima-media thickness ( b = 0.53 lesions per +0.1  mm; 95% CI, 0.1-1.0 lesions), 50%-100% carotid stenosis versus no stenosis ( b = 6.6 lesions; 95% CI, 2.3-10.9 lesions), ankle-brachial index ≤ 0.9 versus >0.9 ( b = 4.9 lesions; 95% CI, 1.7-8.0 lesions), and estimated glomerular filtration rate ( b = -0.77 lesions per +10 mL/min; 95% CI, -1.50 to -0.03 lesions). No significant differences in intracranial atherosclerosis burden were found among different categories of vascular disease., Conclusions: Intracranial atherosclerosis was associated with various extracranial markers of atherosclerosis, not supporting a different etiology., (© 2019 by American Journal of Neuroradiology.)

Background and Purpose: High resolution 7T MRI is increasingly used to investigate hippocampal subfields in vivo, but most studies rely on manual segmentation which is labor intensive. We aimed to evaluate an automated technique to segment hippocampal subfields and the entorhinal cortex at 7T MRI., Materials and Methods: The cornu ammonis (CA)1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex were manually segmented, covering most of the long axis of the hippocampus on 0.70-mm(3) T2-weighted 7T images of 26 participants (59 ± 9 years, 46% men). The automated segmentation of hippocampal subfields approach was applied and evaluated by using leave-one-out cross-validation., Results: Comparison of automated segmentations with corresponding manual segmentations yielded a Dice similarity coefficient of >0.75 for CA1, the dentate gyrus, subiculum, and entorhinal cortex and >0.54 for CA2 and CA3. Intraclass correlation coefficients were >0.74 for CA1, the dentate gyrus, and subiculum; and >0.43 for CA2, CA3, and the entorhinal cortex. Restricting the comparison of the entorhinal cortex segmentation to a smaller range along the anteroposterior axis improved both intraclass correlation coefficients (left: 0.71; right: 0.82) and Dice similarity coefficients (left: 0.78; right: 0.77). The accuracy of the automated segmentation versus a manual rater was lower, though only slightly for most subfields, than the intrarater reliability of an expert manual rater, but it was similar to or slightly higher than the accuracy of an expert-versus-manual rater with ∼170 hours of training for almost all subfields., Conclusions: This work demonstrates the feasibility of using a computational technique to automatically label hippocampal subfields and the entorhinal cortex at 7T MRI, with a high accuracy for most subfields that is competitive with the labor-intensive manual segmentation. The software and atlas are publicly available: http://www.nitrc.org/projects/ashs/., (© 2016 by American Journal of Neuroradiology.)

Introduction: Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI., Methods: In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol., Results: Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume., Limitations: A limitation of this study is the small sample size which makes replication necessary., Conclusions: In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: We aimed to examine the cross-sectional and prospective relationship between leisure time physical activity, brain MRI abnormalities and cognitive performance in patients with vascular disease., Methods: Within the SMART-MR study, 1.5 T MRI of the brain and neuropsychological examinations were performed at baseline (n = 1232) and after 3.9 ± 0.4 years follow-up (n = 663). Automatic brain segmentation was used to quantify intracranial (ICV), total brain, ventricular, and white matter lesion (WML) volumes. Brain infarcts were rated visually. Level of physical activity was expressed in metabolic equivalents (MET) hours p/week. With linear regression analysis we examined associations of level of physical activity with brain MRI measures and with cognitive performance, adjusted for potential confounders. For the association with brain infarcts relative risks (RR) were calculated with Poisson regression., Results: At baseline, an increase in physical activity of one SD (39.7 METh/w) was significantly associated with larger total brain volume (B = 0.20% of ICV; 95% CI 0.06; 0.33%). A trend was found for the association of physical activity with smaller ventricular volume (B = -0.04% of ICV; 95% CI -0.09; 0.02%) and with a decreased risk for brain infarcts (RR = 0.91, 95% CI: 0.82-1.02). No association was found with smaller WML volume (B = -0.02% of ICV; 95% CI -0.07; 0.04%). No associations with change in brain structures over time were observed. Also, no associations between physical activity and cognitive performance or cognitive decline were found., Conclusion: These data suggest that leisure time physical activity does not have a significant contribution in preventing or slowing down brain abnormalities and cognitive decline in this cohort of middle-aged individuals already burdened with vascular disease., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The reduction of major depression incidence is a public health challenge., Aim: To develop an algorithm to estimate the risk of occurrence of major depression in patients attending primary health centers (PHC)., Material and Methods: Prospective cohort study of a random sample of 2832 patients attending PHC centers in Concepción, Chile, with evaluations at baseline, six and twelve months. Thirty nine known risk factors for depression were measured to build a model, using a logistic regression. The algorithm was developed in 2,133 patients not depressed at baseline and compared with risk algorithms developed in a sample of 5,216 European primary care attenders. The main outcome was the incidence of major depression in the follow-up period., Results: The cumulative incidence of depression during the 12 months follow up in Chile was 12%. Eight variables were identified. Four corresponded to the patient (gender, age, depression background and educational level) and four to patients' current situation (physical and mental health, satisfaction with their situation at home and satisfaction with the relationship with their partner). The C-Index, used to assess the discriminating power of the final model, was 0.746 (95% confidence intervals (CI = 0,707-0,785), slightly lower than the equation obtained in European (0.790 95% CI = 0.767-0.813) and Spanish attenders (0.82; 95% CI = 0.79-0.84)., Conclusions: Four of the factors identified in the risk algorithm are not modifiable. The other two factors are directly associated with the primary support network (family and partner). This risk algorithm for the incidence of major depression provides a tool that can guide efforts towards design, implementation and evaluation of effectiveness of interventions to prevent major depression.

Summary: MR imaging at 7T has a high sensitivity for cerebral microbleed detection. We identified mIP processing conditions with an optimal balance between the number of visually detected microbleeds and the number of sections on 7T MR imaging. Even with optimal mIP processing, the limited size of some of the microbleeds and the susceptibility effects of other adjacent structures were a challenge for visual detection, which led to a modest inter-rater agreement, mainly due to missed microbleeds. Automated lesion-detection techniques may be required to optimally benefit from the increased spatial resolution offered by 7T MR imaging.

Background and Purpose: The detection of microbleeds differs strongly between studies, due to differences in scan protocol. This study aims to compare the visualization of microbleeds with 3D T2*-weighted imaging at 1.5T with 3D dual-echo T2*-weighted imaging at 7T., Materials and Methods: Thirty-four patients (29 male; mean age, 58 ± 12 years) with atherosclerotic disease from the Second Manifestations of ARTerial Disease study were included. 3D T2*-weighted imaging at 1.5T and dual-echo T2*-weighted imaging at 7T were done in all patients. The presence and number of definite microbleeds were recorded on minimal intensity projections. Inter- and intraobserver reliability was assessed with Cohen κ test and the ICC. The difference in presence and number of microbleeds was tested with the McNemar test and Wilcoxon signed rank test., Results: The interobserver ICC at 7T was 0.61 and the intraobserver ICC was 0.94, whereas at 1.5T the interobserver ICC was 0.50 and the intraobserver ICC was 0.59. Microbleeds were detected in significantly more patients on 7T (50%) than on 1.5T scans (21%) (P = .001). The number of microbleeds was also higher at 7T (median, 0.5; range, 0-5) than on 1.5T (median, 0.0; range, 0-6) (P = .002)., Conclusions: 3D dual-echo T2*-weighted imaging at 7T results in better and more reliable detection of microbleeds compared with 3D T2*-weighted imaging at 1.5T.

Context: Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied., Objective: To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause., Design and Setting: The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands., Participants: A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia., Main Outcome Measures: Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause., Results: During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed., Conclusion: Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.

Objectives: To review studies that have reported on the prevalence of memory complaints and the relationship between memory complaints and impairment or decline (dementia) in elderly individuals., Data Sources and Study Selection: All publications in the English language relating to memory complaints, memory impairment, cognitive disorder and dementia in MEDLINE, PSYCHLIT and EMBASE computerized databases, together with a search of relevant citations., Data Synthesis: The prevalence of memory complaints, defined as everyday memory problems, shows a large variation of approximately 25 - 50%. A high age, female gender and a low level of education are generally associated with a high prevalence of memory complaints. In community-based samples of elderly subjects an association has been found between memory complaints and memory impairment, after adjustment for depressive symptomatology. Memory complaints predict dementia after a follow-up of at least 2 years, in particular in those with mild cognitive impairment, defined as Mini Mental State Examination (MMSE) > 23. Memory complaints in highly educated elderly subjects may be predictive of dementia even when there is no indication of cognitive impairment on short cognitive screen tests. The shift in methodology which is noticeable in the recently published major studies is discussed as a possible explanation for the established association between memory complaints and decline in memory (or dementia) in elderly subjects. Three methodological factors, in particular, are responsible for the results: community-based sampling, longitudinal design and the treatment of variables such as depression, cognitive impairment and level of education., Conclusion: Memory complaints in elderly people should no longer be considered merely as an innocent age-related phenomenon or a symptom of depression. Instead, these complaints deserve to be taken seriously, at least as a possible early sign of dementia., (Copyright 2000 John Wiley & Sons, Ltd.)

Background and Objective: In an earlier study we observed that a depressive syndrome was highly predictive of developing Alzheimer's disease (AD) in older persons with normal baseline cognition and higher levels of education. We interpreted these findings as the depression being an early noncognitive manifestation of AD in persons with more cognitive reserve. The present study examines whether specific symptoms of depression can be identified that predict AD among older subjects with higher levels of education., Design and Participants: In the community-based Amsterdam Study of the Elderly (AMSTEL), a sample of 3,147 nondemented persons with normal cognition, 65 to 84 years old, was selected and divided into subjects with >8 years and < or =8 years of education. At baseline, the presence or absence of 12 specific symptoms of depression was assessed. At follow-up, patients with incident AD were diagnosed according to DSM-IV criteria in a two-step diagnostic procedure., Results: After an average follow-up of 3.2 years, 1,911 persons were reevaluated, of whom 22 with > 8 years and 31 with < or =8 years of education had developed AD. Multivariate logistic regression analyses showed that among persons with >8 years of education depressed mood and subjective bradyphrenia were strongly associated with incident AD. No association between depressive symptoms and AD was observed among subjects with < or =8 years of education., Conclusions: Both depressed mood and subjective bradyphrenia seem to indicate subclinical AD in older people with higher levels of education. Clinicians should be alert that in these persons, AD may become apparent within a relatively short period of time.