Relations between location and type of intracranial atherosclerosis and parenchymal damage.

The aim of this study was to assess the relation between location and type of intracranial atherosclerosis (ICAS) and cortical microinfarcts (CMIs) and macroinfarcts in 18 patients presenting with ischemic stroke (n = 12) or transient ischemic attack (TIA) (n = 6) using 7 tesla MR imaging. The protocol included: 3D T2-weighted FLAIR and 3D T1-weighted Magnetization-Preparation Inversion Recovery Turbo Spin Echo sequence. ICAS lesions and infarcts were scored by two raters. The relation between ICAS lesions, calculated ratios of ICAS lesion characteristics, location, and infarcts were examined using linear regression analyses. A total number of 75 ICAS lesions (all patients), 101 CMIs (78% of patients), and 31 macroinfarcts (67% of patients) were found. Seventy-six and sixty-five percent of the CMIs and macroinfarcts, respectively, were found in the same vascular territory as the ICAS lesions (p = 0.977, p = 0.167, respectively). A positive correlation existed between the number of macroinfarcts and CMIs (p < 0.05). In patients with macroinfarcts, we found more concentric (p < 0.01) and diffuse (p < 0.05) type of ICAS lesions. A high prevalence of brain tissue lesions, both macroinfarcts and CMIs, were found in patients with ICAS. Macroinfarcts were found to be related to specific ICAS lesion types. The type of ICAS lesion seems to be promising as a marker for ICAS patients at higher risk of future infarcts.

Distribution and natural course of intracranial vessel wall lesions in patients with ischemic stroke or TIA at 7.0 Tesla MRI.

OBJECTIVES: Previous studies using intracranial vessel wall MRI techniques showed that over 50 % of patients with ischemic stroke or TIA had one or more intracranial vessel wall lesions. In the current study, we assessed the preferential location of these lesions within the intracranial arterial tree and their potential changes over time in these patient groups. METHODS: Forty-nine patients with ischemic stroke (n = 25) or TIA (n = 24) of the anterior cerebral circulation underwent 7.0 T MRI, including a T1-weighted magnetization-preparation inversion recovery turbo-spin-echo (MPIR-TSE) sequence within one week and approximately one month after symptom onset. Intracranial vessel wall lesions were scored for multiple locations within the arterial tree and differences between one-week and one-month images. RESULTS: At baseline, 132 intracranial vessel wall lesions were found in 41 patients (84 %), located primarily in the anterior cerebral circulation (74 %), with a preferential location in the distal internal carotid artery and M1 and M2 segments of the middle cerebral artery. During follow-up, presence or enhancement patterns changed in 14 lesions (17 %). CONCLUSIONS: A large burden of intracranial vessel wall lesions was found in both the anterior and posterior cerebral circulation. Most lesions were found to be relatively stable, possibly indicating a more generalized atherosclerotic process. KEY POINTS: • Intracranial vessel wall lesions are present in patients with varying cerebrovascular diseases. • Intracranial vessel wall 7.0 T MRI provides information on preferential location and natural course. • Distal ICA and M1 and M2 segments of MCA are predilection sites. • 83 % of lesions found remained stable, possibly indicating more generalized atherosclerosis.

Global brain atrophy but not hippocampal atrophy is related to type 2 diabetes.

AIMS: It has been suggested that in patients with type 2 diabetes mellitus (T2DM), brain atrophy is most pronounced in the hippocampus, but this has not been investigated systematically. The present pooled analysis of three studies examined if hippocampal atrophy is more prominent than global brain atrophy in patients with T2DM relative to controls. METHODS: Data were derived from a cohort study of patients with vascular disease (SMART-Medea (T2DM=120; no T2DM=502)), and from two case-control studies (UDES1 (T2DM=61; controls=30) and UDES2 (T2DM=54; controls=53)). In SMART-Medea and UDES1, hippocampal volume was obtained by manual tracing on 1.5 Tesla (T) MRI scans. Total brain and intracranial volume (ICV) were determined by an automated segmentation method. In UDES2, hippocampal and total brain volume were determined by FreeSurfer and ICV by manual segmentation on 3 T MRI scans. RESULTS: The pooled analyses, adjusted for age and sex, showed a significant negative relation between T2DM and total brain-to-ICV ratio (standardized mean difference=-1.24%, 95% CI: -1.63; -0.86), but not between T2DM and hippocampal-to-ICV ratio (0.00%, 95% CI: -0.01; 0.00) or between T2DM and hippocampal-to-total brain volume ratio (0.01%, 95% CI: -0.01; 0.02). In patients with T2DM no associations were found between brain volume measures and HbA1c or memory. CONCLUSION: Patients with T2DM had greater brain atrophy but not hippocampal atrophy, compared to controls. These findings do not support specific vulnerability of the hippocampus in patients with T2DM.

Cerebral microvascular lesions on high-resolution 7-Tesla MRI in patients with type 2 diabetes.

Cerebral small vessel disease, including microvascular lesions, is considered to play an important role in the development of type 2 diabetes mellitus (T2DM)-associated cognitive deficits. With ultra-high field MRI, microvascular lesions (e.g., microinfarcts and microbleeds) can now be visualized in vivo. For the current study, 48 nondemented older individuals with T2DM (mean age 70.3 ± 4.1 years) and 49 age-, sex-, and education-matched control subjects underwent a 7-Tesla brain MRI scan and a detailed cognitive assessment. The occurrence of cortical microinfarcts and cerebral microbleeds was assessed on fluid-attenuated inversion recovery and T1-weighted and T2*-weighted images, respectively, compared between the groups, and related to cognitive performance. Microinfarcts were found in 38% of control subjects and 48% of patients with T2DM. Microbleeds were present in 41% of control subjects and 33% of patients (all P > 0.05). The presence and number of microinfarcts or microbleeds were unrelated to cognitive performance. This study showed that microvascular brain lesions on ultra-high field MRI are not significantly more common in well-controlled patients with T2DM than in control subjects.

Brain imaging in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and dementia. Brain imaging may provide important clues about underlying processes. This review focuses on the relationship between T2DM and brain abnormalities assessed with different imaging techniques: both structural and functional magnetic resonance imaging (MRI), including diffusion tensor imaging and magnetic resonance spectroscopy, as well as positron emission tomography and single-photon emission computed tomography. Compared to people without diabetes, people with T2DM show slightly more global brain atrophy, which increases gradually over time compared with normal aging. Moreover, vascular lesions are seen more often, particularly lacunar infarcts. The association between T2DM and white matter hyperintensities and microbleeds is less clear. T2DM has been related to diminished cerebral blood flow and cerebrovascular reactivity, particularly in more advanced disease. Diffusion tensor imaging is a promising technique with respect to subtle white matter involvement. Thus, brain imaging studies show that T2DM is associated with both degenerative and vascular brain damage, which develops slowly over the course of many years. The challenge for future studies will be to further unravel the etiology of brain damage in T2DM, and to identify subgroups of patients that will develop distinct progressive brain damage and cognitive decline.

Cerebral microbleeds are not associated with long-term cognitive outcome in patients with transient ischemic attack or minor stroke.

BACKGROUND: Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. METHODS: Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n=397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n=280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n=48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. RESULTS: The mean age was 65±12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70±9 vs. 64±12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p<0.05). The mean TICS score was 35.3±5.9 for patients with microbleeds (n=29) and 34.6±5.2 for patients without microbleeds (n=251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0±10.8 for patients with microbleeds (n=9) and 63.1±12.9 for patients without microbleeds (n=39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient ß: -0.12 (-0.23 to 0.00); p=0.04] and with lower IQCODE score [0.51 (0.19-0.83); p=0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p=0.01). CONCLUSIONS: In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease.

Polymorphisms in ACVRL1 and endoglin genes are not associated with sporadic and HHT-related brain AVMs in Dutch patients.

We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.

Microbleeds as a predictor of intracerebral haemorrhage and ischaemic stroke after a TIA or minor ischaemic stroke: a cohort study.

OBJECTIVES: We examined whether patients with cerebral microbleeds on MRI, who started and continued antithrombotic medication for years, have an increased risk of symptomatic intracerebral haemorrhage (ICH). DESIGN: Prospective cohort study. SETTINGS: Multicentre outpatient clinics in the Netherlands. PARTICIPANTS: We followed 397 patients with newly diagnosed transient ischaemic attack (TIA) or minor ischaemic stroke receiving anticoagulants or antiplatelet drugs. 58% were men. The mean age was 65.3 years. 395 (99%) patients were white Europeans. MRI including a T2*-weighted gradient echo was performed within 3 months after start of medication. 48 (12%) patients had one or more microbleeds. They were followed every 6 months by telephone for a mean of 3.8 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was a symptomatic ICH. Secondary outcome were all strokes, ischaemic stroke, myocardial infarct, death from all vascular causes, death from non-vascular causes and death from all causes. RESULTS: Five patients (1%) suffered from a symptomatic ICH. One ICH occurred in a patient with microbleeds at baseline (adjusted HR 2.6, 95% CI 0.3 to 27). The incidence of all strokes during follow-up was higher in patients with than without microbleeds (adjusted HR 2.3, 95% CI 1.0 to 5.3), with a dose-response relationship. The incidences of ischaemic stroke, vascular death, non-vascular death and death of all causes were higher in patients with microbleeds, but not statistically significant. CONCLUSIONS: In our cohort of patients using antithrombotic drugs after a TIA or minor ischaemic stroke, we found that microbleeds on MRI are associated with an increased risk of future stroke in general, but we did not find an increased risk of symptomatic ICH.

Semi-Automated Detection of Cerebral Microbleeds on 3.0 T MR Images.

Cerebral microbleeds are associated with vascular disease and dementia. They can be detected on MRI and receive increasing attention. Visual rating is the current standard for microbleed detection, but is rater dependent, has limited reproducibility, modest sensitivity, and can be time-consuming. The goal of the current study is to present a tool for semi-automated detection of microbleeds that can assist human raters in the rating procedure. The radial symmetry transform is originally a technique to highlight circular-shaped objects in two-dimensional images. In the current study, the three-dimensional radial symmetry transform was adapted to detect spherical microbleeds in a series of 72 patients from our hospital, for whom a ground truth visual rating was made by four raters. Potential microbleeds were automatically identified on T2*-weighted 3.0 T MRI scans and the results were visually checked to identify microbleeds. Final ratings of the radial symmetry transform were compared to human ratings. After implementing and optimizing the radial symmetry transform, the method achieved a high sensitivity, while maintaining a modest number of false positives. Depending on the settings, sensitivities ranged from 65%-84% compared to the ground truth rating. Rating of the processed images required 1-2 minutes per participant, in which 20-96 false positive locations per participant were censored. Sensitivities of individual raters ranged from 39%-86% compared to the ground truth and required 5-10 minutes per participant per rater. The sensitivities that were achieved by the radial symmetry transform are similar to those of individual experienced human raters, demonstrating its feasibility and usefulness for semi-automated microbleed detection.

Multi-sequence whole-brain intracranial vessel wall imaging at 7.0 tesla.

OBJECTIVES: Intracranial vessel wall magnetic resonance imaging (MRI) may improve the diagnosis of vessel wall abnormalities. Current methods are hampered by limited coverage and few contrast weightings. We present a multi-sequence protocol with whole-brain coverage for vessel wall imaging on 7.0-T MRI. METHODS: A modified magnetisation-preparation inversion recovery turbo-spin-echo (MPIR-TSE) sequence was used to obtain proton density (PD)-, T1-, and T2-weighting with 190-mm whole-brain coverage. Three observers independently scored the visibility of arterial vessel walls in five healthy volunteers, and compared the conspicuity and image contrast of all sequences. Clinical applicability was demonstrated in 17 patients with cerebrovascular disease. RESULTS: Conspicuity was good for all acquisitions, with best scores for the original limited-coverage sequence, followed by whole-brain coverage T2-, PD- and T1-weighted sequences, respectively. Mean vessel wall/background MR signal intensity ratios for all whole-brain sequences were similar, with higher scores for the limited-coverage MPIR-TSE sequence. Signal intensity ratios were highest in patients, for the whole-brain T1-weighted sequence. CONCLUSIONS: The whole-brain multi-sequence vessel wall protocol can assess intracranial arterial vessel walls with full brain coverage, for different image contrast weightings. These sequences could eventually characterise intracranial vessel wall abnormalities similar to current techniques for assessing carotid artery plaques. KEY POINTS: - Intracranial vessel wall imaging using MRI improves diagnosis of cerebrovascular diseases. - Conventional 7-T MRI sequences cannot image the whole cerebral arterial tree. - New whole-brain 7-T MRI sequences compare favourably with smaller-coverage sequences. - These whole-brain sequences can demonstrate the entire cerebral arterial tree. - These sequences should help in the diagnosis of vessel wall abnormalities.

Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes.

Patients with type 2 diabetes often show slowing of information processing. Disruptions in the brain white matter network, possibly secondary to vascular damage, may underlie these cognitive disturbances. The current study reconstructed the white matter network of 55 nondemented individuals with type 2 diabetes (mean age, 71 ± 4 years) and 50 age-, sex-, and education-matched controls using diffusion magnetic resonance imaging-based fiber tractography. Graph theoretical analysis was then applied to quantify the efficiency of these networks. Patients with type 2 diabetes showed alterations in local and global network properties compared with controls (P < 0.05). These structural network abnormalities were related to slowing of information processing speed in patients. This relation was partly independent of cerebrovascular lesion load. This study shows that the approach of characterizing the brain as a network using diffusion magnetic resonance imaging and graph theory can provide new insights into how abnormalities in the white matter affect cognitive function in patients with diabetes.

Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study.

OBJECTIVE: To examine whether type 2 diabetes is associated with microstructural abnormalities in specific cerebral white matter tracts and to relate these microstructural abnormalities to cognitive functioning. RESEARCH DESIGN AND METHODS: Thirty-five nondemented older individuals with type 2 diabetes (mean age 71 ± 5 years) and 35 age-, sex-, and education-matched control subjects underwent a 3 Tesla diffusion-weighted MRI scan and a detailed cognitive assessment. Tractography was performed to reconstruct several white matter tracts. Diffusion tensor imaging measures, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups and related to cognitive performance. RESULTS: MD was significantly increased in all tracts in both hemispheres in patients compared with control subjects (P < 0.05), reflecting microstructural white matter abnormalities in the diabetes group. Increased MD was associated with slowing of information-processing speed and worse memory performance in the diabetes but not in the control group after adjustment for age, sex, and estimated IQ (group × MD interaction, all P < 0.05). These associations were independent of total white matter hyperintensity load and presence of cerebral infarcts. CONCLUSIONS: Individuals with type 2 diabetes showed microstructural abnormalities in various white matter pathways. These abnormalities were related to worse cognitive functioning.

Cerebral haemodynamics, cognition and brain volumes in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and brain abnormalities on MRI. The underlying mechanisms are unclear. We examined the relationship between cerebral haemodynamics (cerebral blood flow (CBF) and cerebrovascular reactivity (CVR)) and cognitive performance and brain volumes in patients with T2DM, at baseline and after four years. METHODS: 114 patients with T2DM, aged 56-80 years, underwent a detailed cognitive assessment and MRI scan. In 68 patients the evaluation was repeated after four years. CBF (two-dimensional flow-encoded phase-contrast MRI) and CVR (carbogen breathing response middle cerebral artery; transcranial Doppler) were measured at baseline. Cognitive performance was expressed as composite z-score and regression based index score. Brain volumes were measured on MRI by automated segmentation. The relationship of haemodynamics with cognition and brain volumes was examined with linear regression analyses adjusted for age, sex and IQ. RESULTS: Mean CVR was 51.8% ± 18.0% and mean rCBF 53.3 ± 11.3 ml/min/100 ml brain tissue. CBF was associated with baseline cognitive performance (standardized regression coefficient ß (95% CI): 0.17 (0.00; 0.32) and total brain volume (0.23 (0.05; 0.41)). No correlation was found between CVR and baseline cognitive performance. Neither CBF nor CVR predicted change in cognition (CBF 0.11 (-0.21; 0.44); CVR 0.07 (-0.21; 0.36)) or total brain volume (CBF 0.09 (-0.22; 0.39); CVR 0.13 (-0.13; 0.40)) over four years. CONCLUSIONS: CBF was associated with impaired cognition and total brain volume in cross-sectional analyses, but did not predict changes in cognition or brain volumes over time. Apparently, alterations in cerebral haemodynamics play no major etiological role in cognitive decline or change in brain volumes in non-demented individuals with T2DM.

High prevalence of cerebral microbleeds at 7Tesla MRI in patients with early Alzheimer's disease.

The prevalence of microbleeds on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD) is lower than that of its presumed pathological correlate, cerebral amyloid angiopathy. We examined 18 patients with early AD or mild cognitive impairment (MCI) and 18 non-demented controls with ultra-high field strength 7Tesla MRI, to assess if the actual prevalence of microbleeds could be higher than is currently reported. One or more microbleeds were visualized in 78% of the MCI/AD patients and in 44% of the controls (p = 0.04). 7Tesla MRI shows that presence of microbleeds may be the rule, rather than exception in patients with MCI/AD.

Cerebral microinfarcts: a systematic review of neuropathological studies.

Vascular cognitive impairment is an umbrella term for cognitive dysfunction associated with and presumed to be caused by vascular brain damage. Autopsy studies have identified microinfarcts as an important neuropathological correlate of vascular cognitive impairment that escapes detection by conventional magnetic resonance imaging (MRI). As a frame of reference for future high-resolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors, cognitive decline and dementia. We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer's disease (43%), and demented patients with both Alzheimer-type and cerebrovascular pathology (33%) compared with nondemented older individuals (24%). In many patients, multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor, or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 µm to a few mm, which is within the detection limit of current high-resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular cognitive impairment.

Intracranial vessel wall imaging at 7.0-T MRI.

BACKGROUND AND PURPOSE: Conventional imaging methods cannot depict the vessel wall of intracranial arteries at sufficient resolutions. This hampers the evaluation of intracranial arterial disease. The aim of the present study was to develop a high-resolution MRI method to image intracranial vessel wall. METHODS: We developed a volumetric (3-dimensional) turbo spin-echo (TSE) sequence for intracranial vessel wall imaging at 7.0-T MRI. Inversion recovery was used to null cerebrospinal fluid to increase contrast with the vessel wall. Magnetization preparation was applied before inversion to improve signal-to-noise ratio. Seven healthy volunteers and 35 patients with ischemic stroke or transient ischemic attack underwent imaging to test the magnetization preparation inversion recovery TSE sequence. Gadolinium-based contrast agent (Gadobutrol, 0.1 mL/kg) was administered to assess possible lesion enhancement in the patients. RESULTS: The walls of intracranial arterial vessels could be visualized in all volunteers and patients with good contrast between wall, blood, and cerebrospinal fluid. The quality of the vessel wall depiction was independent of the vessel orientation relative to the plane of acquisition. In 21 of the 35 patients, a total number of 52 intracranial vessel wall lesions were identified. Eleven of the 52 lesions showed enhancement after contrast administration. Only 14 of the 52 lesions resulted in stenosis of the arterial lumen. CONCLUSIONS: Intracranial vessel wall and its pathology can be depicted with the magnetization preparation inversion recovery TSE sequence at 7.0 T. The magnetization preparation inversion recovery TSE sequence will make it possible to study the role of intracranial arterial wall pathology in ischemic stroke. Clinical Trial Registration Information- URL: http://www.trialregister.nl/trialreg/index.asp. Unique identifier: NTR2119.

[Imaging of small cerebral blood vessels using 7-Tesla MRI]. / Beeldvorming kleine hersenbloedvaten met 7 Tesla-MRI.

MRI equipment with a magnet having a field strength of 7 Tesla (7-T) has been in use for several years at the University Medical Centre, Utrecht, the Netherlands. 7-Tesla MR imaging provides new opportunities for imaging the brain and its vasculature. The enhanced resolution and the possibilities for angiography of the smallest cerebral vessels without using contrast media are particularly of interest for patients with cerebral small-vessel disease. Microthrombi may be visualised in the perforating cerebral arteries in patients with a lacunar infarct. This technique could have a considerable impact on the classification of several types of lacunar infarcts and could lead to better customised therapies.

Cerebral cortical thickness in patients with type 2 diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with cortical atrophy on MRI. It is unclear whether this atrophy is global or if there are areas with particular vulnerability. We compared regional cortical atrophy between patients with T2DM and controls and examined determinants of atrophy within the T2DM group. METHODS: Cortical surface, volume and thickness were compared between 56 patients with T2DM and 30 controls, both globally and regionally, using the Freesurfer software package. The relationship between atrophy and HbA1c levels, diabetes duration, hypertension, a history of macrovascular disease and cerebral small vessel disease was analyzed within the T2DM group, with linear regression analyses, adjusted for age and gender. RESULTS: Total cortical surface, total cortical volume and mean cortical thickness for both hemispheres were consistently lower in the T2DM group (between group differences: 0.5-4%), but the effects were only significant in the right hemisphere (p<0.05). Post-hoc regional analyses revealed significant differences in the hippocampal region (between group differences cortical thickness and volume: 5-20.5%) and the middle temporal gyrus (between group differences cortical surface and volume ~8%). Within the T2DM group, smaller cortical thickness of the hippocampal region was associated with cerebral small vessel disease, but no associations between vascular or metabolic determinants and cortical atrophy were found. CONCLUSION: The effects of T2DM on cortical grey matter are most pronounced in the temporal lobe. This should be considered when atrophy is used as a marker in etiological or therapeutical studies.