Jeroen de Bresser

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.

Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes

OBJECTIVE Type 2 diabetes is associated with a moderate degree of cerebral atrophy and a higher white matter hyperintensity (WMH) volume. How these brain-imaging abnormalities evolve over time is unknown. The present study aims to quantify cerebral atrophy and WMH progression over 4 years in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 55 patients with type 2 diabetes and 28 age-, sex-, and IQ-matched control participants had two 1.5T magnetic resonance imaging scans with a 4-year interval. Volumetric measurements of total brain, peripheral cerebrospinal fluid (CSF), lateral ventricles, and WMH were performed with k-nearest neighbor–based probabilistic segmentation. All volumes were expressed as percentage of intracranial volume. Linear regression analyses, adjusted for age and sex, were performed to compare brain volumes between the groups and to identify determinants of volumetric change within the type 2 diabetic group. RESULTS At baseline, patients with type 2 diabetes had a significantly smaller total brain volume and larger peripheral CSF volume than control participants. In both groups, all volumes showed a significant change over time. Patients with type 2 diabetes had a greater increase in lateral ventricular volume than control participants (mean adjusted between-group difference in change over time [95% CI]: 0.11% in 4 years [0.00 to 0.22], P = 0.047). CONCLUSIONS The greater increase in lateral ventricular volume over time in patients with type 2 diabetes compared with control participants shows that type 2 diabetes is associated with a slow increase of cerebral atrophy over the course of years.

MRBrainS challenge: online evaluation framework for brain image segmentation in 3T MRI scans

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65–80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand.

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.

Accelerated cognitive decline in patients with type 2 diabetes: MRI correlates and risk factors

Type 2 diabetes mellitus is associated with an increased risk of cognitive decline and dementia. We examined brain imaging correlates and vascular and metabolic risk factors of accelerated cognitive decline in patients with type 2 diabetes.

A comparison of MR based segmentation methods for measuring brain atrophy progression

Automated brain segmentation methods with a good precision and accuracy are required to detect subtle changes in brain volumes over time in clinical applications. However, the ability of established methods such as SIENA, US and kNN to estimate brain volume change have not been compared on the same data, nor been evaluated with ground-truth manual segmentations. We compared measurements of brain volume change between SIENA, US and kNN in terms of precision (repeatability) and accuracy (ground-truth) using one baseline and two repeated follow-up 1.5 T MRI scans after 4 years of 10 subjects. The coefficient of repeatability (brain volume/volume change) was larger for US (29.6 cc/2.84%) than for kNN (4.9 cc/0.31%) and SIENA (-/0.92%). In terms of absolute brain volume measurements US and kNN showed good correlation with the manual segmentations and with each other (all Spearmans correlation coefficients ρ≥0.96; all p<0.001). Concerning brain volume changes, SIENA showed a good (ρ=0.82; p=0.004), kNN a moderate (ρ=0.60; p=0.067) and US a weak (ρ=0.50; p=0.138) correlation with the manual segmentations. For measurements of volume change, SIENA-US (mean correlation coefficient and p-value: ρ=0.28; p=0.442) and US-kNN (ρ=0.17; p=0.641) showed a weak correlation, but correlation was fairly good for kNN-SIENA (ρ=0.65; p=0.048). In conclusion, US and kNN showed a good precision, accuracy and comparability for brain volume measurements. For measurements of volume change, SIENA showed the best performance. kNN is a good alternative if volume change measurements of other brain structures are required.

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.

Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes

Background/Aims: The present study examined the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities over a period of 4 years in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-eight elderly patients with T2DM had 2 cognitive assessments with a 4-year interval. Two MRI scans, performed at the same time as the cognitive assessments, were available from 55 patients. Changes in cognitive performance over time were expressed as a regression-based index (RBI). Automated volumetric measurements of total brain, lateral ventricles and white matter hyperintensities were performed. The relationship between baseline microvascular complications [diabetic retinopathy, peripheral neuropathy or albuminuria (micro- or macroalbuminuria)] and cognition and brain volumes was examined with linear regression analyses adjusted for age and sex (for cognition also for IQ). Results: At baseline, diabetic retinopathy was present in 18% of patients, peripheral neuropathy in 36%, albuminuria in 15%. Retinopathy or neuropathy were not significantly associated with baseline cognition or brain volumes, or changes in these measures over time. Albuminuria was associated with a lower composite RBI score, indicating accelerated cognitive decline (adjusted mean difference between patients with or without albuminuria: –0.58, 95% CI –0.85 to –0.31, p < 0.001). Conclusion: Albuminuria predicted accelerated cognitive decline in patients with T2DM, but other microvascular complications were unrelated to accelerated cognitive decline or brain MRI 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.