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Background and aim To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). Methods We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. Results We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. Conclusion Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

SUMMARY: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20–65 years of age) and follow-up of 17 mutation carriers (30–65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

BACKGROUND CONTEXT: Percutaneous laser disc decompression (PLDD) is a minimally invasive treatment for lumbar disc herniation, with Food and Drug Administration approval since 1991. However, no randomized trial comparing PLDD to conventional treatment has been performed. PURPOSE: In this trial, we assessed the effectiveness of a strategy of PLDD as compared with conventional surgery. STUDY DESIGN/SETTING: This randomized prospective trial with a noninferiority design was carried out in two academic and six teaching hospitals in the Netherlands according to an intent-to-treat protocol with full institutional review board approval. PATIENT SAMPLE: One hundred fifteen eligible surgical candidates, with sciatica from a disc herniation smaller than one-third of the spinal canal, were included. OUTCOME MEASURES: The main outcome measures for this trial were the Roland-Morris Disability Questionnaire for sciatica, visual analog scores for back and leg pain, and the patient's report of perceived recovery. METHODS: Patients were randomly allocated to PLDD (n=57) or conventional surgery (n=58). Blinding was impossible because of the nature of the interventions. This study was funded by the Healthcare Insurance Board of the Netherlands. RESULTS: The primary outcome, Roland-Morris Disability Questionnaire, showed noninferiority of PLDD at 8 (-0.1; [95% confidence interval (CI), -2.3 to 2.1]) and 52 weeks (-1.1; 95% CI, -3.4 to 1.1) compared with conventional surgery. There was, however, a higher speed of recovery in favor of conventional surgery (hazard ratio, 0.64 [95% CI, 0.42-0.97]). The number of reoperations was significantly less in the conventional surgery group (38% vs. 16%). Overall, a strategy of PLDD, with delayed surgery if needed, resulted in noninferior outcomes at 1 year. CONCLUSIONS: At 1 year, a strategy of PLDD, followed by surgery if needed, resulted in noninferior outcomes compared with surgery. (C) 2015 Elsevier Inc. All rights reserved.

Atrophy is regarded a sensitive marker of neurodegenerative pathology. In addition to confirming the well-known presence of decreased global grey matter and hippocampal volumes in Alzheimer's disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimer's disease, and whether such degeneration is associated with cognitive deterioration. In this cross-sectional correlation study, two groups were compared on volumes of seven subcortical regions: 70 memory complainers (MCs) and 69 subjects diagnosed with probable Alzheimer's disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIB's Integrated Registration and Segmentation Tool (FIRST)--algorithm FMRIB's Software Library (FSL). Subsequently, the volumes of the different regions were correlated with cognitive test results. In addition to finding the expected association between hippocampal atrophy and cognitive decline in Alzheimer's disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimer's disease. We also found that the decrease in volume correlated linearly with impaired global cognitive performance. These findings strongly suggest that, beside neo-cortical atrophy, deep grey matter structures in Alzheimer's disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimer's disease.

Background Cerebral white matter hyperintensities on magnetic resonance imaging (MRI) scans have been associated with vascular disease and late-life depression, both in the general population and in psychiatric patients. Therefore, a cerebrovascular etiology for late-onset depression has been hypothesized. However, longitudinal studies on the causal role of white matter hyperintensities in the development of depressive symptoms in elderly adults are lacking. Objective To investigate the relation between white matter hyperintensities and depressive symptoms in elderly subjects at risk of cardiovascular disease. Methods In the Dutch sample of the PROSPER (PROspective Study of Pravastatine in the Elderly at Risk of cardiovascular disease) cohort, 527 non-demented elderly, all aged 70 years or older, received a cranial MRI scan and the 15-item Geriatric Depression Scale, at baseline and 33 months (SD 1.6) later. Results Presence of white matter hyperintensities at baseline was not related to baseline depressive symptoms nor to the development of depressive symptoms during follow-up. Moreover, no association was found between progression of white matter lesion volume and progression of depressive symptoms. Conclusion This longitudinal study does not confirm the involvement of cerebrovascular disease expressed as MRI white matter hyperintensities in the development of depressive symptoms in elderly subjects. Copyright © 2006 John Wiley & Sons, Ltd.

Objective To investigate the relationship between magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE). Methods The study group consisted of 24 female patients (mean age 36 years [range 23–65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated. Results MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H-MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H-MRS and MTI findings, there was no significant correlation between H-MRS results and any other parameter. Conclusion The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.

After successful transsphenoidal surgery for acromegaly, life-long follow-up is required, because 10-15% of patients develop recurrence of disease. We assessed whether it is safe to perform postoperative follow-up with only biochemical evaluation in acromegalic patients initially cured by transsphenoidal surgery. We studied 32 patients cured after transsphenoidal surgery for acromegaly during a follow-up of 8.7 +/- 6.4 yr (mean +/- sd). Serial measurements of serum GH during glucose tolerance test and magnetic resonance imaging (MRI) scans were performed. Serial MRI scans were reevaluated by three independent neuroradiologists, who were blinded for the clinical and biochemical data, for growth of suspected tumor tissue. Twenty-three patients remained biochemically cured in the long term, whereas nine of the 32 patients developed recurrence of disease, indicated by elevated serum GH concentrations during glucose tolerance test and clinical symptoms/signs. None of the 23 patients with long-term biochemical cure showed growth of tumor tissue according to two neuroradiologists, whereas the third neuroradiologist assessed three of 23 patients as having tumor growth despite continuing biochemical cure. In the nine patients with biochemical recurrence, no tumor growth was found in the series of postoperative MRI scans, according to two of the three independent radiologists, whereas the third radiologist found tumor growth in four patients with recurrent disease. In conclusion, in patients with acromegaly, initially cured by transsphenoidal surgery, it appears safe to check for recurrent disease during long-term follow-up of these patients by biochemical markers only.

Objective: We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of MAPT (microtubule-associated protein tau) or GRN (progranulin) mutations. Methods: In this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk of frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, structural MRI, and fMRI. We used voxel-based morphometry and tract-based spatial statistics for voxel-wise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsular, anterior midcingulate, and posterior cingulate cortices. Results: Carriers (n = 39) and noncarriers (n = 36) had similar neuropsychological performance, except for lower Letter Digit Substitution Test scores in carriers. Worse performance on Stroop III, Rivermead Behavioral Memory Test, and Happe Cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy in the right uncinate fasciculus was found in carriers compared with controls. Reductions in functional connectivity between anterior midcingulate cortex and frontoinsula and several other brain regions were found in carriers compared with controls and correlated with higher age in carriers, but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found, except for a small cluster of higher volume in the precentral gyrus in carriers. Conclusions: This study demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.

Summary: The relationship between cognitive deterioration and abnormalities detected by magnetic resonance imaging (MRI) was investigated to determine the radiological correlates of cognitive deterioration in hereditary cerebral hemorrhage with amyloidosis- Dutch type (HCHWA-D). Twenty HCHWA-D subjects (12 patients who had suffered one or more strokes and eight who had not suffered a stroke) were studied with MRI and underwent extensive neuropsychological examination. On MRI the number of focal lesions was counted, and white matter hyperintensities (WMHs) were scored semiquantitatively. A significant correlation between cognitive deterioration and WMH score and number of focal lesions was found. However, cognitive deterioration, WMH score, and the number of focal lesions all increase with age, and therefore their mutual correlation can be explained as an age effect. This study shows that cognitive deterioration in HCHWA-D is not correlated with abnormalities detected by MRI (number of focal lesions and subcortical WMHs) independently of age. Although a contribution of white matter changes and/or focal lesions, possibly in combination with age, to cognitive deterioration cannot be excluded. Cognitive deterioration in these HCHWA-D patients is probably primarily the result of chronic damage of amyloid angiopathy to the brain, to which may be superimposed cognitive impairment from focal cerebral hemorrhage or infarction

The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.

Cerebral deposits of amyloid-β peptides (Aβ) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, Aβ can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar Aβ. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also Aβ itself has been suggested to be responsible for a decrease in the image intensity. In this current study we aim to investigate the MRI properties of the different cerebral Aβ deposits including diffuse plaques and vascular amyloid. Postmortem 60-μm-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain Aβ, were studied. High resolution T2*- and T2-weighted MRI scans and quantitative relaxation maps were acquired using a microcoil on a Bruker 9.4T MRI system. Specific MRI characteristics of each type of Aβ deposit were examined by co-registration of the MRI with Congo Red and Aβ-immunostainings of the same sections. Our results show that only fibrillar Aβ, present in both vascular and parenchymal amyloid, induced a significant change in T2* and T2 values. However, signal changes were not as consistent for all of the vessels affected by CAA, irrespective of possible dyshoric changes. In contrast, the non-fibrillar diffuse plaques did not create any detectable MRI signal changes. These findings are relevant for the interpretation and further development of (quantitative) MRI methods for the detection and follow-up of AD and CAA.

Item does not contain fulltext OBJECTIVE: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [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 magnetic resonance imaging (MRI) in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. METHODS: MR images of the first episode of active NPSLE in 74 patients were retrospectively reviewed. All patients fulfilled the American College of Rheumatology (ACR) 1982 revised criteria for the classification of SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. We excluded patients with a history of brain disease and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms. RESULTS: The principal findings were: 1) focal hyperintensities in white matter (WM) (49% of all patients) or both WM and gray matter (GM) (5% of all patients), 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% of all patients), compatible with an immune response to neuronal components or postseizure changes; and 4) absence of MRI abnormalities, despite signs and symptoms of active disease (42% of all patients). 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 radiographic manifestations may be a good starting point and useful for categorization of patients in further research.

Objective: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons. Methods: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions. Results: People with multiple (>= 2) CMBs had lower Z scores on tests of processing speed (beta-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62). Conclusion: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community. Neurology (R) 2010;75:2221-2228

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.

Background: Cerebral amyloid angiopathy (CAA) typically presents with lobar intracerebral macrohemorrhages (ICH) or microbleeds (MBs). Several case reports also found superficial siderosis (SS) in patients with CAA. We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage. Methods: We retrospectively analyzed the T2*-weighted MRIs of 38 patients with histopathologically proven CAA and of 22 control patients with histopathologically proven non-CAA ICHs regarding the presence of ICHs, MBs, and SS. We compared the sensitivity and specificity of the classic Boston criteria to that of modified criteria, which included SS as a criterion. Results: ICHs were present in 71% of the patients with CAA, and in all control patients. MBs were found in 47.4% of patients with CAA and in 22.7% of controls. SS was detected in 60.5% of patients with CAA, but in none of the controls. The classic criteria had a sensitivity of 89.5% for CAA-related hemorrhage, while inclusion of SS increased their sensitivity to 94.7% (not significant). On the contrary, the specificity of the Boston criteria was 81.2% both for the classic and for the modified criteria. Conclusions: Superficial siderosis (SS) occurs with high prevalence in cerebral amyloid angiopathy (CAA) and is rare in non-CAA forms of intracerebral hemorrhages. Thus, we propose that inclusion of SS in the Boston criteria might enhance their sensitivity for CAA-related hemorrhage without loss of specificity. Neurology (R) 2010; 74: 1346-1350

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.

Background and purpose: Incidental foci of signal loss suggestive of cerebral microbleeds (CMBs) are frequent findings on gradient echo T2* weighted MRI (T2* MRI) of patients with haemorrhagic or ischaemic stroke. There are few prevalence data on older populations. This paper reports on the prevalence and location of CMBs in a community based cohort of older men and women (born 1907–1935) who participated in the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population based cohort study that followed the Reykjavik Study Methods: As part of the examination, all eligible and consenting cohort members underwent a full brain MRI, and blood was drawn for genotyping. Results are based on the first 1962 men (n = 820) and women (n = 1142), mean age 76 years, with complete MRI and demographic information available. Results: Evidence of CMBs was found in 218 participants (11.1% (95% CI 9.8% to 12.6%)); men had significantly more CMBs than women (14.4% vs 8.8%; p = 0.0002, age adjusted). The prevalence of CMBs increased with age (p = 0.0001) in both men (p = 0.006) and women (p = 0.007). CMBs were located in the cerebral lobes (70%), the basal ganglia region (10.5%) and infratentorium (18.6%). Having a CMB was significantly associated with a homozygote Apo E 44 genotype (p = 0.01). Conclusion: Cerebral microbleeds are common in older persons. The association with homozygote Apo E 4 genotype and finding a relative predominance in the parietal lobes might indicate an association with amyloid angiopathy.

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.

The objective of this study is to investigate the presence of autoantibodies cross-reacting with the NR2 subunit of the N-methyl-d-aspartate (NMDA) glutamate receptor in plasma samples of patients with systemic lupus erythematosus (SLE), in their healthy first-degree relatives and in healthy unrelated individuals and to determine whether these autoantibodies are specific for lupus patients in general or for the subgroup of SLE patients with neuropsychiatric (NP) manifestations. Plasma samples were collected from 51 lupus patients (19 with and 32 without NP manifestations), 161 first-degree relatives and 55 healthy unrelated controls. Antibodies to a linear peptide of the NR2 subunit of the NMDA receptor were determined by enzyme-linked immunosorbent assay. A significant difference in mean antibody reactivity between SLE patients and healthy unrelated controls ( P < 0.01) and between firstdegree relatives and healthy unrelated controls ( P < 0.001) was found. No difference was found between lupus patients and their first-degree relatives or between lupus patients with and without NP symptoms. In this study, anti-NMDA receptor autoantibodies show more specificity for lupus patients (but not for selected patients with NP symptoms) and their first-degree relatives than for healthy controls, indicating a familial basis to mount an immune response to this peptide. Lupus (2007) 16, 329—334.

To investigate relations between EEG measures and performance on tests of global cognition, memory, language and executive functioning.Twenty-two controls, 18 patients with mild cognitive impairment (MCI) and 16 with probable Alzheimer's disease (AD) underwent neuropsychological and EEG investigations. We used the following EEG measures: theta relative power during eyes closed, alpha reactivity during memory activation (i.e. the percentual decrease in alpha power as compared to eyes closed) and alpha coherence during eyes closed and memory activation.Theta relative power was increased in AD patients as compared with controls (p0.001) and MCI patients (p0.01) and related to decreased performance in all cognitive domains. Alpha reactivity was decreased in AD patients as compared with controls (p0.005) and related to decreased performance on tests of global cognition, memory and executive functioning. Alpha coherence did not differ between groups and was unrelated to cognition.EEG power measures were associated with decreased performance on tests of global cognition, memory, language and executive functioning, while coherence measures were not.The EEG yielded several power measures related to cognitive functions. These EEG power measures might prove useful in prospective studies aimed at predicting longitudinal cognitive decline and dementia.

This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions (‘eyes closed’ and ‘eyes open’) and three memory conditions (‘word memory’, ‘picture memory’ and ‘animal fluency’). For all conditions, EEG power in the theta (4–8 Hz), lower alpha (8–10.5 Hz) and upper alpha (10.5–13 Hz) bands were expressed as percentile changes compared to ‘eyes closed’. MCI patients showed significantly less decrease in the lower alpha band than controls (p = 0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p = 0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not.

The authors examined the effect of pravastatin 40 mg daily on the progression of ischemic brain lesions using repeated brain MRI. After a mean treatment period of 33 months, there was an increase in total ischemic lesion load of 1.1 cm3 (p < 0.001) in the 270 placebo-treated subjects and 1.1 cm3 (p < 0.001) in the 265 pravastatin-treated subjects. There was no difference between the two treatment groups (p = 0.73).

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.

The role of quantitative image analysis in large clinical trials is continuously increasing. Several methods are available for performing white matter hyperintensity (WMH) volume quantification. They vary in the amount of the human interaction involved. In this paper, we describe a fully automatic segmentation that was used to quantify WMHs in a large clinical trial on elderly subjects. Our segmentation method combines information from 3 different MR images: proton density (PD), T2-weighted and fluid-attenuated inversion recovery (FLAIR) images; our method uses an established artificial intelligent technique (fuzzy inference system) and does not require extensive computations. The reproducibility of the segmentation was evaluated in 9 patients who underwent scan-rescan with repositioning; an inter-class correlation coefficient (ICC) of 0.91 was obtained. The effect of differences in image resolution was tested in 44 patients, scanned with 6- and 3-mm slice thickness FLAIR images; we obtained an ICC value of 0.99. The accuracy of the segmentation was evaluated on 100 patients for whom manual delineation of WMHs was available; the obtained ICC was 0.98 and the similarity index was 0.75. Besides the fact that the approach demonstrated very high volumetric and spatial agreement with expert delineation, the software did not require more than 2 min per patient (from loading the images to saving the results) on a Pentium-4 processor (512 MB RAM).

The authors investigated the progression of white matter hyperintensities (WMHs) in a large population of elderly men and women. After 3 years of follow-up, women had accumulated approximately twice as much deep WMH (DWMH) as men. The progression of periventricular WMH was the same for men and women. Gender differences may affect the pathogenesis of DWMH, which in turn may result in different clinical consequences in women.

Objective To investigate the relationship between quantitative estimates of global brain damage based on magnetization transfer imaging (MTI) and cerebral functioning, as measured by neurologic, psychiatric, and cognitive assessments, as well as disease duration in patients with a history of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods In a clinically heterogeneous group of 24 female patients (age range 19–65 years, mean age 35 years) with a history of NPSLE, the correlation values of several volumetric MTI measures and an estimate of cerebral atrophy, neurologic functioning (Kurtzke's Expanded Disability Status Scale [EDSS]), psychiatric functioning (the Hospital Anxiety and Depression Scale [HADS]), and cognitive functioning (cognitive impairment score [CIS] derived from the revised Wechsler Adult Intelligence Scale), as well as several measures of disease duration were assessed using Pearson's correlation coefficient. Results Quantitative volumetric estimates of global brain damage based on MTI and a measure of global brain atrophy correlated significantly with the EDSS, HADS, and CIS scores. No significant correlation was found between the quantitative estimates of global brain damage and the measures of disease duration. Conclusion The results of this study demonstrate that volumetric MTI parameters and cerebral atrophy reflect functionally relevant brain damage in patients with NPSLE. Furthermore, the absence of a linear relationship between disease duration and results of volumetric MTI measures and atrophy suggests a complicated pattern of accumulating brain damage in patients with NPSLE.

Objective: To investigate the relationships between structural damage in the whole brain, the temporal lobes, and the frontal lobes and cognitive decline at old age. The authors hypothesized that widespread brain damage as quantified using magnetization transfer imaging (MTI) is related to global cognitive decline, whereas regional damage to the temporal lobes is related to memory impairment, and regional damage to the frontal lobes is related to executive dysfunctioning. Methods: Cognitive function of 22 patients with probable AD, 13 patients with mild cognitive impairment (MCI), and 28 elderly controls was assessed using an extensive neuropsychological test battery. Structural damage in the whole brain, the temporal lobes, and the frontal lobes was estimated using volumetric MTI analysis. Associations between MTI measures and neuropsychological tests were investigated using Pearson correlation analysis. Results: MTI measures of the whole brain, as well as the temporal and the frontal lobes, were strongly associated with global cognitive deterioration and impairment in memory, orientation, language, praxis, gnosis, and executive functioning. However, there were no specific cognitive correlates of regional brain damage to the temporal and frontal lobes. Conclusions: Using whole brain volumetric magnetization transfer imaging, the authors demonstrated that cognitive decline in patients with mild cognitive impairment and AD is associated with widespread structural brain damage. As there were no specific relationships between regional brain damage and impairment of specific cognitive functions, pathology in AD and mild cognitive impairment is much more generalized than was expected.

The main causes of dementia at old age are Alzheimer's disease and vascular dementia. The clinical presentations of late-onset Alzheimer's disease and vascular dementia can barely be differentiated. This clinical observation is supported by pathological findings. Late-onset dementia should be considered a multifactorial disease, in which both vascular factors and amyloid dispositions contribute to cognitive decline.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by a mutation at codon 693 of the beta amyloid precursor protein gene. The disease is clinically characterized by strokes and dementia. In addition to cerebral plaques, cerebral amyloid angiopathy is the pathological hallmark. We investigated the correlation between radiological (white matter hyperintensities and focal lesions on magnetic resonance images) and pathological lesions (cerebrovascular amyloid angiopathy and plaques) and the apolipoprotein E genotype in patients with the disease. Twenty-five patients were studied using magnetic resonance imaging, and brain tissue from 8 patients was studied histopathologically. Neither the white matter hyperintensity scores nor the number of focal lesions on magnetic resonance images were associated with the presence of an epsilon4 allele. Nor was a correlation found between the number and type of plaques and the apolipoprotein E genotype. All patients had severe amyloid angiopathy in all cortical areas investigated. This study showed that the apolipoprotein E genotype does not modulate amyloid-related structural lesions in hereditary cerebral hemorrhage with amyloidosis of the Dutch type.

Adhesion between leukemic cells and the vascular endothelium has been suggested to play a role in the development of leukostasis in myelocytic leukemia. To define the role of adhesion molecules on the surface of endothelial cells in leukostasis, we used immunohistochemistry to study the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in lung tissue of 4 patients with pulmonary leukostasis. Lung tissue of 2 patients with myelocytic leukemia without leukostasis and 4 patients with irrelevant nonpulmonary disease was used as a negative control. Positive control tissues included a lymph node with angioimmunoblastic lymphadenopathy and a hyperplastic tonsil. Weak positive staining for ELAM-1 was found in 1 patient in vessels, both with and without leukostasis. Expression of VCAM-1 and ICAM-1 in all patients tested was similar to that in the negative controls. The results of this study suggest that activation of endothelium, with increased expression of the endothelial adhesion molecules under study, is not a prerequisite for the development of pulmonary leukostasis in leukemia.

Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply.