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Background: This study aimed to compare direct aspiration, stent retriever, and the combined thrombectomy technique on clinical, safety, and technical outcomes in late-window stroke patients included in the MR CLEAN-LATE trial., Methods: This post hoc analysis of the MR CLEAN-LATE trial included patients treated with direct aspiration, stent retriever, or combined thrombectomy technique as first-line approach. Primary outcome was the modified Rankin Scale (mRS) score at 90 days follow-up, and compared between the three groups with ordinal logistic regression analysis. Secondary outcomes included mortality at 90 days, total technique switches, procedure time, recanalization rate measured with the expanded thrombolysis in cerebral infarction (eTICI) score, and symptomatic intracranial hemorrhage (sICH). Predefined variables were used for adjustments., Results: In the MR CLEAN-LATE trial, 258 patients underwent endovascular treatment and 232 were included in our analyses. The mRS at 90 days did not differ (stent retriever vs. direct aspiration: adjusted common odds ratio (acOR) = 1.35, 95% confidence interval (CI) = 0.73 to 2.50; stent retriever vs. combined: acOR = 1.13, 95% CI = 0.64 to 2.00; direct aspiration vs. combined: acOR = 1.19, 95% CI = 0.64 to 2.21). Direct aspiration thrombectomy was accompanied with more switches to another technique compared to the stent retriever (adjusted odds ratio (aOR) = 6.50, 95% CI = 2.52 to 16.8) or combined group (aOR = 4.67, 95% CI = 1.80 to 12.1) and with higher sICH rates compared to the combined technique (13% vs. 2.5%; aOR = 8.19, 95% CI = 1.49 to 45.1). Mortality, procedure time, and eTICI did not differ., Conclusion: Stent retriever, direct aspiration, or the combined thrombectomy technique as first-line approach showed no differences in clinical outcome in late-window stroke patients. Direct aspiration was accompanied with higher sICH rates and more switcher to another technique compared to the combined group., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.H.v.Z. reports speaker fees from Stryker, Cerenovus, and Nicolab and consulting fees from Philips (all paid to institution); participated in the advisory boards of WeTrust (Philips) and ANAIS (Anaconda) (all paid to institution); and participated in the advisory boards of InEcxtremis (CHU Montpellier, Montpellier, France) and DISTAL (University Hospital Basel, Basel, Switzerland), studies for which no payments were received. B.J.E. reports funding from the Netherlands Organisation for Health Research and Development and Health Holland Top Sector Life Sciences & Health and unrestricted grants from Nicolab (all paid to institution). All other authors declare no competing interests.

Background: Women with anterior circulation large vessel occlusion (LVO) have been reported to have worse outcomes after endovascular treatment (EVT) than men. Whether these disparities also exist in LVO of the posterior circulation is yet uncertain. We assessed sex differences in clinical, technical, and safety outcomes of EVT in posterior circulation LVO., Methods: We used data of patients with posterior circulation LVO included in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2018). Primary outcome was the modified Rankin Scale (mRS) score at 90 days assessed with multivariable ordinal regression analysis. Secondary outcomes included favorable functional outcome (mRS ≤3), functional independence (mRS ≤2), death within 90 days, National Institutes of Health Stroke Scale (NIHSS) score 24-48 hours postintervention, complications, successful reperfusion (extended Thrombolysis in Cerebral Ischemia 2B-3), and procedure duration analyzed with multivariable logistic and linear regression analyses., Results: We included 264 patients (42% women). Compared with men, women were older (median age 68 vs 63 years), more often had prestroke disability (mRS ≥1: 37% vs 30%), and received intravenous thrombolytics less often (45% vs 56%). Clinical outcomes were similar between sexes (adjusted (common) OR (aOR) 0.82, 95% CI 0.51 to 1.34; favorable functional outcome 50% vs 43%, aOR 1.31, 95% CI 0.77 to 2.25; death 32% vs 29%, aOR 0.98, 95% CI 0.52 to 1.84). In addition, NIHSS score after 24-48 hours (median 7 vs 9), successful reperfusion (77% vs 73%), and complications did not differ between men and women., Conclusions: Outcomes in women treated with EVT for posterior circulation LVO were similar compared with men despite less favorable baseline characteristics in women. Therefore men and women may benefit equally from EVT., Competing Interests: Competing interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MJHW reports funding from NWO/ZonMw (VIDI 91717337 and Aspasia). JH reports funding from the Dutch Heart Foundation (CEI 2018T070). CBLMM reports funding from the TWIN Foundation, CVON/Dutch Heart Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker, all outside the submitted work (paid to institution). In addition, he is shareholder of Nicolab. IRvdW reports consulting fees from Philips, Medtronic, and Neurophyxia. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus, all paid to the institution. The other authors had no conflicting interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could optimize in-hospital surveillance time points and duration. The aim of this study was to delineate the probability of sICH over time and to identify factors associated with its timing., Patients and Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial and MR CLEAN Registry. We included adult patients who underwent EVT for an anterior circulation large vessel occlusion within 6.5 h of stroke onset. In patients with sICH (defined as ICH causing an increase of ⩾4 points on the National Institutes of Health Stroke Scale [NIHSS]), univariable and multivariable linear regression analysis was used to identify factors associated with the timing of sICH. This was defined as the time between end of EVT and the time of first CT-scan on which ICH was seen as a proxy., Results: SICH occurred in 205 (6%) of 3391 included patients. Median time from end of EVT procedure to sICH detection on NCCT was 9.0 [IQR 2.9-22.5] hours, with a rapidly decreasing incidence after 24 h. None of the analyzed factors, including baseline NIHSS, intravenous alteplase treatment, and poor reperfusion at the end of the procedure were associated with the timing of sICH., Conclusion: SICHs primarily occur in the first hours after EVT, and less frequently beyond 24 h. Guidelines that recommend to perform frequent neurological assessments for at least 24 h after intravenous alteplase treatment can be applied to ischemic stroke patients treated with EVT., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DD and AvdL report funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. CM: received funds from TWIN Foundation (related to this project, paid to institution); and from CVON/Dutch Heart Foundation, Stryker, European Commission, Health Evaluation Netherlands (unrelated; all paid to institution). CM is shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical imaging analysis. WvZ reports speaker fees from Stryker, Nicolab and Cerenovus, both paid to institution. BR reports funding from the Dutch Heart Foundation, and The Netherlands Organisation for Health Research and Development, all paid to institution., (© European Stroke Organisation 2022.)

Background: Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion., Methods: We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 - TBV/ICV) × 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation., Results: We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97-3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03-3.74] in the middle tertile vs. 3.15 [95% CI: 1.59-6.24] in the highest tertile)., Conclusion: Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment.

Introduction: Prehospital stroke scales have been proposed to identify stroke patients with a large vessel occlusion to allow direct transport to an intervention centre capable of endovascular treatment (EVT). It is unclear whether these scales are able to detect not only proximal, but also more distal treatable occlusions. Our aim was to assess the sensitivity of prehospital stroke scales for different EVT-eligible occlusion locations in the anterior circulation., Patients and Methods: The MR CLEAN Registry is a prospective, observational study in all centres that perform EVT in the Netherlands. We included adult patients with an anterior circulation stroke treated between March 2014 and November 2017. We used National Institutes of Health Stroke Scale scores at admission to reconstruct previously published prehospital stroke scales. We compared the sensitivity of each scale for different occlusion locations. Occlusions were assessed with CT angiography by an imaging core laboratory blinded to clinical findings., Results: We included 3021 patients for the analysis of 14 scales. All scales had the highest sensitivity to detect internal carotid artery terminus occlusions (ranging from 0.21 to 0.97) and lowest for occlusions of the M2 segment (0.08 to 0.84, p-values < 0.001). Discussion and conclusion: Although prehospital stroke scales are generally sensitive for proximal large vessel occlusions, they are less sensitive to detect more distal occlusions., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. AvdL reports funding from Stryker. BvdW has received fees for consultation from Bayer, Boehringer Ingelheim, and LivaNova., (© European Stroke Organisation 2021.)

Background: Antiplatelet therapy may increase the risk of symptomatic intracranial hemorrhage after endovascular treatment for ischemic stroke but may also have a beneficial effect on functional outcome. The aim of this study is to compare safety and efficacy outcomes after endovascular treatment in patients with and without prior antiplatelet therapy., Methods: We analyzed patients registered in the MR CLEAN Registry between March 2014 and November 2017, for whom data on antiplatelet therapy were available. We used propensity score nearest-neighbor matching with replacement to balance the probability of receiving prior antiplatelet therapy between the prior antiplatelet therapy and no prior antiplatelet therapy group and adjusted for baseline prognostic factors to compare these groups. Primary outcome was symptomatic intracranial hemorrhage. Secondary outcomes were 90-day functional outcome (modified Rankin Scale), successful reperfusion (extended thrombolysis in cerebral infarction score ≥2B) and 90-day mortality., Results: Thirty percent ( n  = 937) of the 3154 patients were on prior antiplatelet therapy, who were matched to 477 patients not on prior antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 74/937 (7.9%) patients on prior antiplatelet therapy and in 27/477 (5.6%) patients without prior antiplatelet therapy adjusted odds ratio 1.47, 95% confidence interval 0.86-2.49. No associations were found between prior antiplatelet therapy and functional outcome (adjusted common odds ratio 0.87, 95% confidence interval 0.65-1.16), successful reperfusion (adjusted odds ratio 1.23, 95% confidence interval 0.77-1.97), or 90-day mortality (adjusted odds ratio 1.15, 95% confidence interval 0.86-1.54)., Conclusion: We found no evidence of an association of prior antiplatelet therapy with the risk of symptomatic intracranial hemorrhage after endovascular treatment, nor on functional outcome, reperfusion, or mortality. A substantial beneficial or detrimental effect of antiplatelet therapy on clinical outcome cannot be excluded. A randomized clinical trial comparing antiplatelet therapy versus no antiplatelet therapy is needed.

Background: Persistent carotid-basilar connections have a prevalence of 0.14%. Recognizing such persistent fetal anastomoses between the carotid and the vertebrobasilar circulation is of great importance because they are reportedly associated with an increased prevalence of intracranial aneurysms., Methods: We report the case of a 15-year-old female patient who presented with a World Federation of Neurosurgical Societies grade 5 subarachnoid hemorrhage from an aneurysm at the junction of a persistent primitive hypoglossal artery and the posterior inferior cerebellar artery origin. Supratentorially, unfortunately, there was no parenchymal blush or cortical venous return. Eventually, a multidisciplinary decision was made to withdraw care., Results: Fifty-seven cases were reported in the literature to date of persistent hypoglossal arteries, 16 of which presented with an associated aneurysm, 5 with an arteriovenous malformation, and 6 with a subarachnoid hemorrhage. Our case is the youngest patient reported so far. Hypoplasia or aplasia of the vertebral artery often were encountered (36 and 13 cases, respectively), as well as carotid artery stenosis (15 cases)., Conclusions: Although uncommon, it is important to recognize persistent carotid-basilar connections, since they have a considerable hemodynamic impact on the posterior cerebral circulation via the carotid system. A critical reduction in the carotid blood flow will, therefore, have ischemic consequences in the posterior cerebral territories. In addition, such connections might be associated with anomalies of the vessel wall and be predisposed to aneurysm formation. The endovascular neurointerventionalist, as well as the vascular and skull base neurosurgeon, need to be aware of their anatomy and variations., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cerebral venous sinus thrombosis is a rare cause of stroke, which is routinely treated with systemic heparin. Unfavourable outcome is often seen in severe cases. Therefore alternative treatment methods should be explored in these patients. Due to the risk of haemorrhagic complications, treatment without administration of thrombolytics is of particular interest. This report presents a case of successful mechanical thrombectomy, without the use of thrombolytics, in a comatose patient with cerebral venous sinus thrombosis.

Little is known on the natural history of ruptured isolated aneurysms of the posterior spinal artery (PSA). To date, only a few of such cases have been described in the literature. This paper aims to assess the most appropriate management strategy, based on the available literature and two new cases. In one of these, treatment was postponed until day 33, when angiography showed slight growth of the aneurysm. In the other, conservative treatment, requested by the patient, was successful. From these data, we conclude that treatment strategies for ruptured PSA aneurysms may vary. Aside from the recommendation by others to perform prompt surgical treatment, we suggest an alternative clinical paradigm allowing for the evaluation of the early clinical course. This may preclude the unnecessary treatment of spontaneously regressing lesions and still allows for appropriate treatment for persistent lesions.

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.

Background and Purpose: To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible differences based on a cerebral amyloid angiopathy-type and nonlobar distribution of microbleeds., Methods: We included 435 subjects who were participants from the nested MRI substudy of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were applied to estimate the risk of overall, cardiovascular-related, and stroke-related death associated with microbleeds in general and microbleeds with a lobar distribution suggestive of the presence of cerebral amyloid angiopathy. The corresponding Kaplan-Meier survival curves were calculated., Results: Subjects with >1 CMB had a 6-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 5.97; 95% CI, 1.60-22.26; P=0.01). The diagnosis of nonlobar microbleeds was associated with >2-fold risk of cardiovascular death compared to subjects without microbleeds (hazard ratio, 2.67; 95% CI, 1.23-5.81; P=0.01). Subjects with probable cerebral amyloid angiopathy-type microbleeds had >7-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 7.20; 95% CI, 1.44-36.10; P=0.02)., Conclusions: This is the first study investigating the association between microbleeds and risk of overall, cardiovascular-related, and stroke-related mortality in an elderly population. Our findings indicate that the diagnosis of microbleeds is potentially of clinical relevance. Larger studies are needed to expand our observations and to address potential clinical implications and cost-benefits of such a policy.

Background and Purpose: Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow., Materials and Methods: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min., Results: We found a significant correlation between tCBF in mL/min and both age (r = -.124; p = p

Background/aims: Vascular pathology is increasingly seen as a factor contributing to the development of Alzheimer's disease (AD). With this in mind we hypothesized that this vascular pathology could be directly detected in the arteries contributing to the cerebral circulation of mild cognitive impairment (MCI) and AD patients by means of wall shear stress (WSS) measurements., Methods: In this study we investigated the mean wall shear stress (MWSS), diastolic wall shear stress (DWSS) and systolic wall shear stress (SWSS) in the carotid and basilar arteries of control subjects (mean age: 72; SD: 8.8), patients suffering from MCI (mean age: 76; SD: 6.7), and patients suffering from AD (mean age: 72; SD: 8.2) that were consecutively referred to our outpatient memory clinic using in-house developed software on gradient echo phase-contrast MRI sequences., Results: We found that all these parameters were significantly lower in the carotid arteries of patients suffering from AD or MCI when compared to control subjects. In the basilar artery only DWSS was lower in MCI or AD patients compared to control subjects. In none of the arteries a difference was found for any WSS parameter between MCI and AD patients. WSS parameters were significantly associated (corrected for age and sex) with the degree of cognitive impairment., Conclusion: Increased vascular pathology, as expressed by lower WSS measures, was found in patients suffering from MCI and AD compared to normal controls. This might point to the involvement of vascular pathology in the development of AD., (Copyright 2009 S. Karger AG, Basel.)

In this study we investigated patterns of hypointense basal ganglia on T2*-weighted magnetic resonance imaging (MRI) in 413 non-demented elderly (range: 70-82 years, mean 77 years; male/female: 177/239). In addition, we assessed associations between these patterns and age-related changes in the brain. Three patterns were noted: hypointensity limited to the globus pallidus (group I; n=30; 7%), hypointensity of both globus pallidus and putamen (group II; n=272; 66%), and hypointensity of globus pallidus, putamen and caudate nucleus (group III; n=111; 27%). Group III demonstrated a higher volume of white matter hyperintensities, more atrophy, decreased whole brain magnetization transfer ratios and increased T2-values compared to groups I and II. No differences were observed between groups I and II. From this study we conclude that hypointensity of the caudate nucleus is associated with a higher load of age-related cerebral changes. These data suggest that hypointensity of the caudate nucleus could be a new biomarker of age-related changes in the brain.

Objective: To establish differences in basal ganglia and thalamic volume between preclinical carriers and non-carriers of the Huntington's disease (HD) gene and to link the volume to motor, cognitive and behavioural characteristics in carriers., Methods: Sixteen HD gene carriers without overt clinical motor signs and 14 non-gene carriers underwent clinical evaluation and a MRI scan. Volumes of the caudate nucleus, putamen, gobus pallidus and thalamus were measured using T1-weighted MR images. Motor, cognitive and behavioural functioning was assessed using the Unified Huntington's Disease Rating Scale (UHDRS), cognitive testing and the Beck Depression Inventory (BDI-II)., Results: Volumes of the caudate nucleus, putamen and globus pallidus were significantly smaller in carriers than in non-carriers while no differences between groups were found on clinical evaluation. In gene carriers smaller globus pallidus volume was associated with more motor abnormalities. A smaller putamen volume correlated significantly with worse psychomotor function on the Symbol Digit Modalities Task and the Trail Making Test B., Conclusions: In line with previous research we demonstrated that basal ganglia abnormalities precede overt disease manifestation of HD. Besides we showed that smaller basal ganglia volumes are related to subtle motor abnormalities and worse psychomotor performance in gene carriers without clinical diagnosis. Motor and psychomotor measures may be suitable clinical markers in future neuroprotective trials when combined with volumetric imaging.

Background: To define the cardiovascular risk factors for cerebral microbleeds and to investigate the relationship between microbleeds on the one hand, and the volume of age-related white matter hyperintensities (WMH) and atrophy on the other in an elderly population., Methods: Four hundred and thirty-nine elderly subjects (age range: 72-85; mean: 77) suffering from vascular disease or at high risk for developing this condition were included in this study. For each subject the number and localization of the microbleeds was recorded., Results: The prevalence of microbleeds in this study was 24%. We found age and a history of hypertension to be risk factors for microbleeds. After regional subdivision systolic blood pressure was found to be a risk factor for microbleeds located in the basal ganglia. A history of hypertension was more prevalent in patients with corticosubcortical and basal ganglia microbleeds. Magnetic resonance imaging risk factors associated with one or more microbleeds were total WMH volume, subcortical WMH volume, and periventricular WMH volume. Total WMH volume and periventricular WMH volume were risk factors for corticosubcortical microbleeds and basal ganglia microbleeds., Conclusion: A high prevalence of microbleeds was found in a population of patients suffering from vascular disease or at high risk for developing this condition. Age, hypertension and WMH were the most important risk factors for microbleeds, especially when located in the corticosubcortial junction or in the basal ganglia., (Copyright 2008 S. Karger AG, Basel.)

Background and Purpose: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline., Materials and Methods: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage., Results: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition., Conclusion: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.

Objective: To assess whether structural brain damage as detected by magnetization transfer imaging (MTI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is located in the gray matter (GM) and/or the white matter (WM)., Methods: Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive function participated in this study. GM and WM segmentations were generated from dual fast spin-echo MR images. These masks were co-registrated to MT images for volumetric MTI-analysis of the GM and WM., Results: AD patients had a lower GM volume than controls. Both MCI and AD patients had more structural brain damage in both GM and WM than subjects with normal cognition. Cerebral lesion load in both GM and WM was associated with the degree of cognitive impairment., Conclusion: Using MTI, structural brain changes that are related to cognitive impairment could be demonstrated in both GM and WM of patients with AD and MCI. These results suggest that cerebral changes are present in GM and WM even before patients are clinically demented.

Background and Purpose: Detection of longitudinal changes in white matter hyperintensities (WMH) by using visual rating scales is problematic. We compared a widely used visual rating scale with a volumetric method to study longitudinal white matter changes., Methods: WMH were assessed with the visual Scheltens scale and a volumetric method in 100 elderly subjects aged 70-81 years for whom repetitive MR images were available with an interval of 33 (SD, 1.4) months. Reliability was determined by intraclass correlation coefficients. To examine the sensitivity of both the visual and volumetric method, we calculated Spearman rank correlations of WMH ratings and volume measurements with age., Results: Reliability of the visual rating scale was good, whereas reliability of the volumetric measurement was excellent. For baseline measurements of WMH, we found weaker associations between WMH and age when assessed with the visual scale (r = 0.20, P = .045) than with the volumetric method (r = 0.31, P = .002). Longitudinal evaluation of WMH assessments showed regression in 26% of the subjects when analyzed with the visual rating scale against 12% of the subjects when using volumetric measurements. Compared with the visual rating, the correlation between progression in WMH and age was twice as high when using the volumetric measurement (r = 0.19, P = .062 and r = 0.39, P < .001, respectively)., Conclusion: Volumetric measurements of WMH offer a more reliable, sensitive, and objective alternative to visual rating scales in studying longitudinal white matter changes.