J. van der Grond

Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: an MRI study

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 Alzheimers disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimers 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 Alzheimers disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIBs Integrated Registration and Segmentation Tool (FIRST)—algorithm FMRIBs 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 Alzheimers disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimers 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 Alzheimers disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimers disease.

Fully automatic segmentation of white matter hyperintensities in MR images of the elderly.

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).

Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes

Aims/hypothesisThe determinants of cerebral complications of type 2 diabetes are unclear. The present study aimed to identify metabolic and vascular factors that are associated with impaired cognitive performance and abnormalities on brain MRI in patients with type 2 diabetes.MethodsThe study included 122 patients and 56 controls. Neuropsychological test scores were divided into five cognitive domains and expressed as standardised z values. Brain MRI scans were rated for white matter lesions (WML), cortical and subcortical atrophy, and infarcts. Data on glucose metabolism, vascular risk factors and micro- and macrovascular disease were collected.ResultsPatients with type 2 diabetes had more cortical (pu2009<u20090.001) and subcortical (pu2009<u20090.01) atrophy and deep WML (pu2009=u20090.02) than the control group and their cognitive performance was worse. In multivariate regression analyses within the type 2 diabetes group, hypertension (pu2009<u20090.05) and a history of vascular events (pu2009<u20090.01) were associated with worse cognitive performance, while statin use was associated (pu2009<u20090.05) with better performance. Retinopathy and brain infarcts on MRI were associated with more severe cortical atrophy (both pu2009<u20090.01) and statin use with less atrophy (pu2009<u20090.05). Insulin level and brain infarcts were associated with more severe WML and statin use with less severe WML (all pu2009<u20090.05).Conclusions/interpretationType 2 diabetes is associated with modest impairments in cognition, as well as atrophy and vascular lesions on MRI. This ‘diabetic encephalopathy’ is a multifactorial condition, for which atherosclerotic (macroangiopathic) vascular disease is an important determinant. Chronic hyperglycaemia, hyperinsulinaemia and hypertension may play additional roles.

Neuropsychiatric systemic lupus erythematosus: lessons learned from magnetic resonance imaging

OBJECTIVEnThe 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.nnnMETHODSnMR 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.nnnRESULTSnThe 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).nnnCONCLUSIONnSeveral 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.

Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington's disease.

Objectives: To investigate the function–structure relationship of white matter within different stages of Huntingtons disease (HD) using diffusion tensor imaging (DTI). Experimental design: From the TRACK‐HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age‐matched to two healthy control groups; all underwent 3‐T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. Principle observations: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 – P < 0.005), sensorimotor (P < 0.01 – P < 0.005), and prefrontal region (P < 0.01). Conclusions: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks. Hum Brain Mapp, 2012.

Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study

Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years). Design Prospective cohort study. Setting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands. Participants 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits. Main outcome measures Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured. Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P<0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors. Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age.

EEG and MRI correlates of mild cognitive impairment and Alzheimer's disease

OBJECTIVEnTo investigate whether cognitive function in the spectrum of normal aging to Alzheimers disease is better reflected in MRI or EEG measures, or a combination of both.nnnMETHODSnCognitive functions were tested in 33 elderly subjects: 10 with probable Alzheimers disease, 11 with mild cognitive impairment and 12 controls. Structural brain parameters were derived from conventional MRI and a quantitative MR technique called magnetization transfer imaging. The EEG provided measures of brain function. We performed multiple linear regression analyses to relate EEG and MRI parameters to global cognition, memory, language and psychomotor speed.nnnRESULTSnThe model showed EEG alpha reactivity during eyes open to be the primary factor associated with global cognition, memory and language skills. Brain atrophy was the primary factor associated with psychomotor speed. Furthermore, EEG alpha reactivity during eyes open explained significant additional variability in psychomotor speed.nnnCONCLUSIONnEEG and MRI are each associated with different aspects of cognitive function and complement each other in their relations to psychomotor speed.

Origin and reduction of motion and f0 artifacts in high resolution T2*-weighted magnetic resonance imaging: application in Alzheimer's disease patients.

The altered iron concentration in many neurodegenerative diseases such as Alzheimers disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the transverse relaxation rate. Heavily T(2)*-weighted imaging sequences at high magnetic field strength (7T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T(2)*-weighted sequences at 7T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T(2)*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24+/-13%.

Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging.

ObjectiveTo evaluate, with the use of magnetic resonance imaging (MRI), whether aortic pulse wave velocity (PWV) is associated with cardiac left ventricular (LV) function and mass as well as with cerebral small vessel disease in patients with type 1 diabetes mellitus (DM).Materials and methodsWe included 86 consecutive type 1 DM patients (49 male, mean age 46.9u2009±u200911.7xa0years) in a prospective, cross-sectional study. Exclusion criteria included aortic/heart disease and general MRI contra-indications. MRI of the aorta, heart and brain was performed for assessment of aortic PWV, as a marker of aortic stiffness, systolic LV function and mass, as well as for the presence of cerebral white matter hyperintensities (WMHs), microbleeds and lacunar infarcts. Multivariate linear or logistic regression was performed to analyse the association between aortic PWV and outcome parameters, with covariates defined as age, gender, mean arterial pressure, heart rate, BMI, smoking, DM duration and hypertension.ResultsMean aortic PWV was 7.1u2009±u20092.5xa0m/s. Aortic PWV was independently associated with LV ejection fraction (ßu2009=u2009-0.406, Pu2009=u20090.006), LV stroke volume (ßu2009=u2009-0.407, Pu2009=u20090.001), LV cardiac output (ßu2009=u2009-0.458, Pu2009=u20090.001), and with cerebral WMHs (Pu2009<u20090.05). There were no independent associations between aortic stiffness and LV mass, cerebral microbleeds or lacunar infarcts.ConclusionAortic stiffness is independently associated with systolic LV function and cerebral WMHs in patients with type 1 DM.

Cerebral microbleeds and cognitive functioning in the PROSPER study

Objectives: Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. Methods: For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. Results: We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. Conclusions: Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning.