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Background: Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Purpose: Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Study Type: Prospective-observational. Population: Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence: 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. Assessment: To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Statistical Tests: Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Results: Healthy aging was associated with decreased BOLD amplitude (beta = -0.711) and prolonged time to baseline (beta = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion: Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers.

Background: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co-morbidity with Alzheimer's disease. So far, DMVs have not been evaluated in CAA. Objective: To evaluate DMVs in Dutch-type hereditary CAA (D-CAA) mutation carriers and controls, in relation to MRI markers associated with D-CAA. Methods: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density were quantified on 7 Tesla 3D susceptibility weighted MRI in pre-symptomatic D-CAA mutation carriers (n = 8), symptomatic D-CAA mutation carriers (n = 8), and controls (n = 25). HemorrhagicMRImarkers (cerebral microbleeds, intracerebral hemorrhages, cortical superficial siderosis, convexity subarachnoid hemorrhage), non-hemorrhagic MRI markers (white matter hyperintensities, enlarged perivascular spaces, lacunar infarcts, cortical microinfarcts), cortical grey matter perfusion, and diffusion tensor imaging parameters were assessed in D-CAA mutation carriers. Univariate general linear analysis was used to determine associations between DMV parameters and MRI markers. Results: QuantitativeDMVparameters length, tortuosity, inhomogeneity, and density did not differ between pre-symptomatic D-CAA mutation carriers, symptomatic D-CAA mutation carriers, and controls. No associations were found between DMV parameters and MRI markers associated with D-CAA.Conclusion: This study indicates that vascular amyloid-beta deposition does not affectDMVparameters. In patients with CAA, DMVs do not seem to play a role in the pathogenesis of MRI markers associated with CAA.

ObjectiveTo identify common genetic variants associated with the presence of brain microbleeds (BMBs).MethodsWe performed genome-wide association studies in 11 population-based cohort studies and 3 case–control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.ResultsBMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21–1.45]; p = 2.5 × 10−10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19–1.50]; p = 1.0 × 10−6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86–1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.ConclusionsGenetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p=2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials. White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients ( n = 29 females, 75 years [SD 3]) and 219 controls ( n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group ( P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (β-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume.

BackgroundImpairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the risk of long-term mortality in dementia-free older subjects. Moreover, we investigated the role of structural brain abnormalities in this association.MethodsWe included 547 dementia-free participants (mean age 78 years, 56.5% male) from the nested magnetic resonance imaging sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were used to model 10-year risk of all-cause, cardiovascular, and noncardiovascular mortality in relation to performance in executive function and memory. Moreover, we evaluated the role of total brain parenchymal volume, cerebral blood flow, white matter hyperintensity, and the presence of microbleeds and infarcts in the link between cognitive function and mortality.ResultsIn the multivariable model, lower performance in executive function was associated with greater risk of all-cause (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.31-1.70), cardiovascular (HR 1.69; 95% CI, 1.36-2.11), and noncardiovascular (HR 1.36; 95% CI, 1.15-1.62) mortality. Similarly, poorer performance in memory tests associated with higher risk of all-cause (HR 1.47; 95% CI, 1.29-1.68), cardiovascular (HR 1.45; 95% CI, 1.15-1.83), and noncardiovascular (HR 1.49; 95% CI, 1.27-1.76) mortality. The associations were similar in subjects with various levels of brain structural abnormalities and cerebral blood flow (all P for interaction ≫ .05).ConclusionsPoorer performance in both executive function and memory tests associates with all-cause, cardiovascular, and noncardiovascular mortality in elderly individuals. This association is independent of cardiovascular risk factors and diseases, brain structural abnormalities, and cerebral blood flow.

Importance In Huntington disease (HD), mutation severity is defined by the length of the CAG trinucleotide sequence, a well-known predictor of clinical onset age. The association with disease trajectory is less well characterized. Quantifiable summary measures of trajectory applicable over decades of early disease progression are lacking. An accurate model of the age-CAG association with early progression is critical to clinical trial design, informing both sample size and intervention timing. Objective To succinctly capture the decades-long early progression of HD and its dependence on CAG repeat length. Design, Setting, and Participants Prospective study at 4 academic HD treatment and research centers. Participants were the combined sample from the TRACK-HD and Track-On HD studies consisting of 290 gene carriers (presymptomatic to stage II), recruited from research registries at participating centers, and 153 nonbiologically related controls, generally spouses or friends. Recruitment was targeted to match a balanced, prespecified spectrum of age, CAG repeat length, and diagnostic status. In the TRACK-HD and Track-On HD studies, 13 and 5 potential participants, respectively, failed study screening. Follow-up ranged from 0 to 6 years. The study dates were January 2008 to November 2014. These analyses were performed between December 2015 and January 2019. Main Outcomes and Measures The outcome measures were principal component summary scores of motor-cognitive function and of brain volumes. The main outcome was the association of these scores with age and CAG repeat length. Results We analyzed 2065 visits from 443 participants (247 female [55.8%]; mean [SD] age, 44.4 [10.3] years). Motor-cognitive measures were highly correlated and had similar CAG repeat length–dependent associations with age. A composite summary score accounted for 67.6% of their combined variance. This score was well approximated by a score combining 3 items (total motor score, Symbol Digit Modalities Test, and Stroop word reading) from the Unified Huntington’s Disease Rating Scale. For either score, initial progression age and then acceleration rate were highly CAG repeat length dependent. The acceleration continues through at least stage II disease. In contrast, 3 distinct patterns emerged among brain measures (basal ganglia, gray matter, and a combination of whole-brain, ventricular, and white matter volumes). The basal ganglia pattern showed considerable change in even the youngest participants but demonstrated minimal acceleration of loss with aging. Each clinical and brain summary score was strongly associated with the onset and rate of decline in total functional capacity. Conclusions and Relevance Results of this study suggest that succinct summary measures of function and brain loss characterize HD progression across a wide disease span. CAG repeat length strongly predicts their decline rate. This work aids our understanding of the age and CAG repeat length–dependent association between changes in the brain and clinical manifestations of HD.

Contains fulltext : 182399.pdf (Publisher’s version ) (Open Access) Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer's disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer's and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

Collaborators (845): Astrid M. Vicente Free PMC article:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369905/ Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI. info:eu-repo/semantics/publishedVersion

Objectives: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson’s disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington’s disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. Methods: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment – short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. Results: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington’s Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. Conclusions: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453–461)

Background and Purpose— Low wall shear stress (WSS) is an early marker in the development of vascular lesions. The present study aims to assess the relationship between diastolic and systolic WSS in the internal carotid artery and periventricular (PWML), deep white matter lesions, and cerebral infarcts (CI). Methods— Early, mid, and late diastolic and peak systolic WSS were derived from shear rate obtained by gradient echo phase contrast magnetic resonance sequences multiplied by individually modeled viscosity. PWML, deep white matter lesions, and CI were derived from proton density (PD), T2, and fluid attenuated inversion recovery (FLAIR) MRI in 329 participants (70–82 years; PROSPER baseline). Analyses were adjusted, if appropriate, for age, gender, intracranial volume, and multiple cardiovascular risk factors. Results— Mid-diastolic WSS was significantly correlated with the presence of PWML (B=−10.15; P =0.006) and CI (B=−2.06; P =0.044), but not with deep white matter lesions (B=−1.30; P =0.050; adjusted for age, gender, WML, and intracranial volume). After adjustment for cardiovascular risk factors, these correlations weakened but remained significant. Systolic WSS was not correlated with any of the cerebrovascular parameters. Conclusions— This study is the first to our knowledge to present a cross-sectional correlation between carotid artery WSS and cerebrovascular pathology such as PWML and CI in a large population. Furthermore, it shows that diastolic hemodynamics may be more important than systolic or mean hemodynamics. Future studies exploring vascular hemodynamic damage should focus on diastolic WSS.

Background and Purpose— Migraine is a risk factor for clinical stroke and for subclinical white matter hyperintensities and infratentorial infarcts. These subclinical lesions are linked to small-vessel pathology. Cerebral microbleeds (CMBs) are another biomarker of small-vessel disease but have not yet been studied in migraine. Methods— Identification of CMBs in 63 migraineurs (25 with aura/35 without aura/3 unknown aura status) and 359 controls (aged, 73–85 years) from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) magnetic resonance imaging study. We assessed the modifying role of migraine in the co-occurrence of CMBs, infarcts, and white matter hyperintensity-load. Results— Infratentorial microbleeds were more prevalent in migraine without aura patients than controls (14% versus 4%). Prevalence of other CMBs, infarcts, and white matter hyperintensities did not differ between groups. Migraineurs with CMBs had more often infarcts than controls with CMBs (65% versus 43%). In comparison with controls with infarcts, migraineurs with infarcts had more commonly CMBs (55% versus 30%). Conclusions— Migraine, notably without aura, is associated with infratentorial CMBs at older age. CMBs and infarcts co-occur more often in migraine than in controls. This supports the hypothesis of small-vessel involvement in migraine pathophysiology.

Background Huntington's disease (HD) is characterised by both regional and generalised neuronal cell loss in the brain. Investigating functional brain connectivity patterns in rest in HD has the potential to broaden the understanding of brain functionality in relation to disease progression. This study aims to establish whether brain connectivity during rest is different in premanifest and manifest HD as compared to controls. Methods At the Leiden University Medical Centre study site of the TRACK-HD study, 20 early HD patients (disease stages 1 and 2), 28 premanifest gene carriers and 28 healthy controls underwent 3 T MRI scanning. Standard and high-resolution T1-weighted images and a resting state fMRI scan were acquired. Using FSL, group differences in resting state connectivity were examined for eight networks of interest using a dual regression method. With a voxelwise correction for localised atrophy, group differences in functional connectivity were examined. Results Brain connectivity of the left middle frontal and pre-central gyrus, and right post central gyrus with the medial visual network was reduced in premanifest and manifest HD as compared to controls (0.05 > p > 0.0001). In manifest HD connectivity of numerous widespread brain regions with the default mode network and the executive control network were reduced (0.05 > p > 0.0001). Discussion Brain regions that show reduced intrinsic functional connectivity are present in premanifest gene carriers and to a much larger extent in manifest HD patients. These differences are present even when the potential influence of atrophy is taken into account. Resting state fMRI could potentially be used for early disease detection in the premanifest phase of HD and for monitoring of disease modifying compounds., Highlights • We applied resting state fMRI in premanifest and manifest Huntington's disease. • Reduced functional brain connectivity was present in premanifest HD gene carriers. • Large regions demonstrate reduced functional brain connectivity in manifest HD. • Medial visual, default mode and executive control networks were affected.

PURPOSE: To evaluate ventricular shape differences along the complete surface of the lateral and third ventricles of persons with subjective memory complaints (MC). MATERIALS AND METHODS: We included 28 controls and 21 persons with MC. FLAIR, T2, and PD-weighted brain MRI scans were acquired at 1.5 Tesla, followed by semi-automated segmentation of the lateral and third ventricles, and local shape difference analysis based on growing and adaptive meshes. Ventricular meshes were used to highlight local areas with significant differences between controls and persons with MC, determined by permutation tests with a predefined threshold (P = 0.01). RESULTS: Compared with control subjects, relevant differences were found in the shape of the ventricular surface adjacent to the thalamus and corona radiata in persons with MC. Before correction for multiple comparisons, relevant differences were also found in the shape of the ventricular surface adjacent to the corpus callosum, hippocampus, and amydala. CONCLUSION: Our findings suggest the presence of localized structural brain differences in patients with subjective memory complaints in the thalamus and the corona radiata. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected.

Objectives: Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. Methods: For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. Results: We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. Conclusions: Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning.

AIM Diffuse white matter injury is not well detected by cranial ultrasonography (CUS). The aim of this study was twofold: (1) to assess in very preterm neonates the predictive values of individual CUS abnormalities for white matter injury on MRI and neurological outcome; (2) to develop a strategy optimizing CUS detection of white matter injury. METHOD Very preterm neonates (n=67; 44 males, 23 females) underwent serial CUS and single MRI. Predictive values of CUS findings for a white matter classification on MRI, individual MRI findings, and neurological outcome at 2 years corrected age were calculated. The effects of timing and frequency of CUS were evaluated. RESULTS Periventricular echodensities (PVEs) predicted abnormal white matter on MRI, but absence of PVEs did not predict absence of white matter changes. Peri-and intraventricular haemorrhage (P/IVH) was highly predictive of abnormal white matter on MRI. Frequency and timing of CUS did not influence predictive values. P/IVH and abnormal ventricular size/shape were reasonably predictive of unfavourable outcome, whereas absence of CUS abnormalities predicted a favorable outcome. INTERPRETATION (1) If PVEs are present, there is a significant chance of abnormal white matter on MRI. (2) Increasing frequency of CUS does not increase its diagnostic performance for white matter injury. (3) P/IVH is highly predictive of abnormal white matter on MRI and reasonably predictive of unfavourable outcome. (4) Absence of PVEs and P/IVH on CUS does not guarantee normal white matter, but predicts a favourable outcome.

Background: The P3 event-related potential (ERP) is presumably partly generated by the basal ganglia. Because degeneration of these brain structures starts many years before clinical disease onset in Huntington's disease (HD), studying the interplay between P3 characteristics and basal ganglia volumes in 'premanifest' carriers might lead to new insights into the disease process. Methods: Fourteen premanifest HD mutation carriers and twelve non-mutation carriers underwent clinical, MRI and P3-ERP investigations. The P3 was measured during the Sustained Attention to Response Task. Results: P3 amplitude and latency did not differ between groups. In carriers, longer P3 latency during Go-trials was strongly associated with smaller caudate, putamen and globus pallidus volumes (r values up to -0.827, P

Background: The basal ganglia, hippocampus, and thalamus are involved in the regulation of human feeding behavior. Recent studies have shown that obesity [body mass index (BMI; in kg/m(2)) > 30] is associated with loss of gray and white matter. Objective: It is unknown whether the subcortical brain structures that are actually involved in feeding behavior also show volume changes in obesity. Therefore, the purpose of this study was to evaluate the volumes of the basal ganglia, hippocampus, and thalamus in obesity. Design: Three-dimensional T1-weighted magnetic resonance imaging scans of the brain were analyzed by using automatic segmentation to measure volumes of the nucleus accumbens, globus pallidus, amygdala, putamen, caudate nucleus, thalamus, and hippocampus in 471 subjects (mean age: 74.4 y; 56% men). Results: Obese subjects had larger left (P = 0.013) and right (P = 0.003) amygdalar volumes and a larger left hippocampal volume (P = 0.040) than did normal-weight subjects (BMI, 25). None of the other subcortical structures differed in size between these groups. After correction for age, sex, smoking, hypertension, and pravastatin use, BMI was associated with left (beta = 0.175, P = 0.001) and right (beta = 0.157, P = 0.001) amygdalar volumes and with left hippocampal volume (beta = 0.121, P = 0.016). Conclusions: This study showed that the amygdala and hippocampus are enlarged in obesity. In consideration of the function of these structures, this finding may indicate that hedonic memories could be of major importance in the regulation of feeding. Because of the cross-sectional design, cause and effect could not be discriminated in this study. Am J Clin Nutr 2011;93:1190-5.

Objective. The aim of this study was to determine whether there are differences in white matter integrity between systemic lupus erythematosus (SLE) patients and healthy controls, as determined using tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging data. Methods. Twelve patients with SLE (mean age 42 years [range 15-61 years]) diagnosed according to the American College of Rheumatology 1982 revised criteria for SLE and 28 healthy controls (mean age 46 years [range 21-61 years]) were included in the study. Magnetic resonance imaging was performed on a 3.0T scanner. Fractional anisotropy (FA) maps were calculated for each patient. TBSS analysis was used to compare the FA maps. The TBSS technique projects the FA data into a common space through the use of an initial approximate nonlinear registration, followed by projection onto an alignment-invariant tract representation (mean FA skeleton). The cluster results were corrected for multiple comparisons across space, and a threshold of significance of 0.05 was used. Results. The white matter of tracts in the inferior fronto-occipital fasciculus, the fasciculus uncinatus, as well as the fornix, the posterior limb of the internal capsule (corticospinal tract), and the anterior limb of the internal capsule (anterior thalamic radiation) of patients with SLE showed reduced integrity as compared with normal subjects. Conclusion. In this preliminary study, the integrity of white matter tracts in areas around limbic structures and in the internal capsule was found to be reduced. Larger studies could improve our understanding of the pathologic mechanisms behind the reduced white matter tract integrity in SLE.

OBJECTIVE:: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE or NPSLE) are highly diverse and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain MRI in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. METHODS:: MRI exams of the first episode of active NPSLE of 74 patients were retrospectively reviewed. All patients fulfilled the revised 1982 ACR criteria for SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. Patients with a history of brain disease, and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms, were excluded. RESULTS:: The principal findings were: 1) focal hyperintensities in WM (49% of all patients) or both WM and GM (5%) suggestive of vasculopathy or vasculitis, 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms, 3) diffuse cortical GM lesions (12%), compatible with an immune response to neuronal components or post-seizure changes, and 4) absence of MRI abnormalities, despite active signs and symptoms (42%). CONCLUSION:: Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiological manifestations may be a good starting point and useful for categorization of patients in further research.

In Huntington’s disease (HD) atrophy of the caudate nucleus and putamen has been described many years before clinical manifestation. Volume changes of the pallidum, thalamus, brainstem, accumbens nucleus, hippocampus, and amygdala are less well investigated, or reported with contradicting results. The aim of our study is to provide a more precise view of the specific atrophy of the subcortical grey matter structures in different stages of Huntington’s disease, and secondly to investigate how this influences the clinical manifestations. All TRACK-HD subjects underwent standardised T1-weighted 3T MRI scans encompassing 123 manifest HD (stage 1, n = 77; stage 2, n = 46), 120 premanifest HD (close to onset n = 58, far from onset n = 62) and 123 controls. Using FMRIB’s FIRST and SIENAX tools the accumbens nucleus, amygdala, brainstem, caudate nucleus, hippocampus, pallidum, putamen, thalamus and whole brain volume were extracted. Results showed that volumes of the caudate nucleus and putamen were reduced in premanifest HD far from predicted onset (>10.8 years). Atrophy of accumbens nucleus and pallidum was apparent in premanifest HD in the close to onset group (0–10.8 years). All other structures were affected to some degree in the manifest group, although brainstem, thalamus and amygdala were relatively spared. The accumbens nucleus, putamen, pallidum and hippocampus had a strong significant correlation with functional and motor scores. We conclude that volume changes may be a sensitive and reliable measure for early disease detection and in this way serve as a biomarker for Huntington’s disease. Besides the caudate nucleus and putamen, the pallidum and the accumbens nucleus show great potential in this respect. Electronic supplementary material The online version of this article (doi:10.1007/s00415-010-5768-0) contains supplementary material, which is available to authorized users.

Objective: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. Methods: From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70-82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. Results: Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). Conclusion: Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity. Neurology (R) 2010;75:997-1002