Manon Brundel

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%), Alzheimers 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.

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.

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.

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.

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.

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.

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 Alzheimers 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.

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

ObjectivesIntracranial 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.MethodsA 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.ResultsConspicuity 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.ConclusionsThe 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.

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 β (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.

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.