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F Barkhof

Publications and source records attributed to F Barkhof.

At least 19 recordsLinked to original sources
PubMed2006

Improved reliability of hippocampal atrophy rate measurement in mild cognitive impairment using fluid registration.

MRI-derived rates of hippocampal atrophy may serve as surrogate markers of disease progression in mild cognitive impairment (MCI). Manual delineation is the gold standard in hippocampal volumetry; however, this technique is time-consuming and subject to errors. We aimed to compare regional non-linear (fluid) registration measurement of hippocampal atrophy rates against manual delineation in MCI. Hippocampi of 18 subjects were manually outlined twice on MRI scan-pairs (interval+/-SD: 2.01+/-0.11 years), and volumes were subtracted to calculate change over time. Following global affine and local rigid registration, regional fluid registration was performed from which atrophy rates were derived from the Jacobian determinants over the hippocampal region. Atrophy rates as derived by fluid registration were computed using both forward (repeat onto baseline) and backward (baseline onto repeat) registration. Reliability for both methods and agreement between methods was assessed. Mean+/-SD hippocampal atrophy rates (%/year) derived by manual delineation were: left: 2.13+/-1.62; right: 2.36+/-1.78 and for regional fluid registration: forward: left: 2.39+/-1.68; right: 2.49+/-1.52 and backward: left: 2.21+/-1.51; right: 2.42+/-1.49. Mean hippocampal atrophy rates did not differ between both methods. Reliability for manual hippocampal volume measurements (cross-sectional) was high (intraclass correlation coefficient (ICC): baseline and follow-up, left and right, >0.99). However, the resulting ICC for manual measurements of hippocampal volume change (longitudinal) was considerably lower (left: 0.798; right: 0.850) compared with regional fluid registration (forward: left: 0.985; right: 0.988 and backward: left: 0.975; right: 0.989). We conclude that regional fluid registration is more reliable than manual delineation in assessing hippocampal atrophy rates, without sacrificing sensitivity to change. This method may be useful to quantify hippocampal volume change, given the reduction in operator time and improved precision.

Aged↗
PubMed2006

Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection?

BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis (aCAS) remains a matter of debate. It seems that not only the degree of stenosis, but also other factors have to be taken in account to improve patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS: The literature pertaining aCAS was reviewed in order to describe the natural history, risk of stroke and benefit of CEA for patients with aCAS in regard to several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors influencing the indication for CEA are severity of stenosis, age, contralateral disease, stenosis progression to >80%, gender, concomitant operations and life expectancy. To improve patient selection investigations will concentrate on plaque characteristics and instability and cerebral hemodynamics and metabolism.

Carotid Stenosis↗
PubMed2006

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.

BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. METHODS: Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, -0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. CONCLUSION: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.

Aged↗
PubMed2006

Consistent resting-state networks across healthy subjects.

Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3%. In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.

Brain↗
PubMed2006

Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.

OBJECTIVE: To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 mug subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months. RESULTS: After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group). CONCLUSIONS: Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.

Adult↗
PubMed2006

Clinical significance of corpus callosum atrophy in a mixed elderly population.

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

Age Factors↗
PubMed2006

CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment.

OBJECTIVE: To study CSF biomarkers, beta-amyloid(1-42) (Abeta(1-42)) and tau, and medial temporal lobe atrophy (MTA) on MRI in their ability to predict dementia in patients with mild cognitive impairment (MCI). METHODS: Fifty-nine MCI patients (49% male, mean age 69+/-8), follow-up 19 months, were included. Baseline CSF levels of Abeta(1-42), tau and MTA-score were dichotomized. RESULTS: Thirty-three (56%) of the MCI patients progressed to dementia, 30 of which had Alzheimer's disease. Lower CSF Abeta(1-42) level, higher CSF-tau and higher MTA-scores at baseline were found in progressed patients. Cox proportional hazards models revealed that abnormal CSF Abeta(1-42), CSF tau and MTA were significantly associated with dementia at follow-up (hazard ratio (95% confidence interval): 4.0 (1.3-12.1), 5.9 (1.6-21.7) and 2.1 (1.0-4.6)). A fourfold higher risk was found for patients with both abnormal CSF biomarkers and MTA compared to patients with either test abnormal. Ninety-four percent of patients with both abnormalities converted to dementia. CONCLUSIONS: These findings suggest an added value of CSF to MRI in the diagnostic work up of patients presenting at a memory clinic.

Aged↗
PubMed2006

Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy.

AIMS/HYPOTHESIS: In addition to nephropathy, retinopathy and peripheral neuropathy, a microvascular complication of type 1 diabetes that may be tentatively referred to as 'diabetic encephalopathy' has gained increasing attention. There is growing evidence that lowered cognitive performance in patients with type 1 diabetes is related to chronic hyperglycaemia rather than recurrent episodes of severe hypoglycaemia, as previously speculated. The aim of our study was to use magnetic resonance imaging (MRI) to establish whether long-term hyperglycaemia, resulting in advanced retinopathy, contributes to structural changes in the brain (reduced grey matter). SUBJECTS, MATERIALS AND METHODS: We applied voxel-based morphometry on magnetic resonance images to compare grey matter density (GMD) between three groups of participants. GMD is used as a marker of cortical atrophy. We compared 13 type 1 diabetic patients with a microvascular complication (i.e. proliferative retinopathy) with 18 type 1 diabetic patients who did not have retinopathy in order to assess the effects of microvascular changes on GMD. Both patient groups were compared with 21 healthy control subjects to assess the effect of diabetes in itself. RESULTS: Patients with diabetic retinopathy showed reduced GMD in the right inferior frontal gyrus and right occipital lobe compared both with patients without retinopathy and with healthy controls (p<0.05). CONCLUSIONS/INTERPRETATION: Our data show that patients with type 1 diabetes, who, as a consequence of chronic hyperglycaemia, had developed advanced retinopathy, also showed increased focal cortical atrophy on brain MRI.

Adult↗
PubMed2006

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

BACKGROUND: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. OBJECTIVE: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. METHODS: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. RESULTS: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. CONCLUSIONS: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Adult↗
PubMed2006

Prevalence and severity of microbleeds in a memory clinic setting.

OBJECTIVE: To determine prevalence and severity of microbleeds (MBs) in a large cohort of patients attending a memory clinic. METHODS: The authors consecutively included patients attending their memory clinic between January 2002 and April 2005. They analyzed prevalence and number of MBs according to demographic, diagnostic, and MRI data. RESULTS: The authors included 772 patients (53% men, age 66 +/- 11). One hundred twenty-seven patients (17%) exhibited at least one MB. The prevalence differed according to diagnostic groups (p < 0.0001): Sixty-five percent of patients with vascular dementia exhibited MBs vs 18% of Alzheimer disease patients, 20% of mild cognitive impairment patients, and 10% of patients with subjective complaints. The presence of MBs was associated with age, white matter hyperintensities, lacunar infarcts, and infarcts. CONCLUSION: The prevalence of microbleeds (MBs) in a large cohort of patients attending a memory clinic is higher than previously described in community samples and lower than reported in stroke patients. This finding of a relatively high proportion of MBs in Alzheimer disease and mild cognitive impairment provides further evidence for the involvement of vascular factors in neurodegenerative diseases such as Alzheimer disease.

Aged↗
PubMed2006

Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord.

BACKGROUND: Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized. METHODS: The authors studied seven patients with Alexander disease, diagnosed based on mutations in the GFAP gene, who presented unusual MRI findings. The authors reviewed clinical history, MRI abnormalities, and GFAP mutations. RESULTS: All patients had juvenile disease onset with signs of brainstem or spinal cord dysfunction. None of the patients had a macrocephaly. The MRI abnormalities were dominated by medulla and spinal cord abnormalities, either signal abnormalities or atrophy. One patient had only minor cerebral white matter abnormalities. A peculiar finding was the presence of a kind of garland along the ventricular wall in four patients. Three patients had an unusual GFAP mutation, one of which was a duplication mutation of two amino acids, and one an insertion deletion. CONCLUSION: Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.

Adolescent↗
PubMed2006

Hippocampal atrophy in Alzheimer disease: age matters.

Hippocampal atrophy is a marker of Alzheimer disease (AD). It remains unclear whether this holds true for younger patients as well. Hippocampal volume was measured on MRI scans of 103 clinically diagnosed AD patients and 73 controls (aged 51 to 85 years). Aging and AD were independently associated with smaller hippocampal volume. Both young and old AD patients have hippocampal atrophy abnormal for age. Age-dependent criteria for hippocampal atrophy, suggestive of AD, are needed.

Aged↗
PubMed2006

Growth-associated protein 43 in lesions and cerebrospinal fluid in multiple sclerosis.

Axonal damage in multiple sclerosis (MS) is correlated to disease progression. Early axonal damage may be compensated for by regenerative processes. Growth-associated protein 43 (GAP-43) is a marker for axonal growth and synaptogenesis in various neurodegenerative diseases. We investigated the expression of GAP-43 in 48 MS grey and white matter lesions of different stages. Decreased GAP-43 expression was found in 74% of the white matter lesions, independent of the lesion stage. In 19 out of 35 white matter lesions, areas of increased GAP-43 expression were present immediately adjacent to the lesions. Increased or unaltered expression was observed in remyelinated lesions. GAP-43 was expressed in neurofilament-positive structures. GAP-43 expression appeared unchanged in grey matter lesions. Macrophages were present in the areas of changed GAP-43 expression. cerebrospinal fluid GAP-43 levels were negatively correlated with magnetic resonance imaging measures of whole-brain atrophy (r = -0.30). In conclusion, these results indicate that decreased GAP-43 immunopositivity reflects axonal damage in MS lesions, which may again be reflected in decreased cerebrospinal fluid levels. The increased levels of GAP-43 in remyelinated or nondemyelinated white matter close to MS lesions may reflect regenerative attempts by damaged axons.

Adult↗
PubMed2006

EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis.

Magnetic resonance (MR)-based techniques are widely used for the assessment of patients with suspected and definite multiple sclerosis (MS). However, despite the publication of several position papers, which attempted to define the utility of MR techniques in the management of MS, their application in everyday clinical practice is still suboptimal. This is probably related, not only, to the fact that the majority of published guidelines focused on the optimization of MR technology in clinical trials, but also to the continuing development of modern, quantitative MR-based techniques, that have not as yet entered the clinical arena. The present report summarizes the conclusions of the 'EFNS Expert Panel of Neuroimaging of MS' on the application of conventional and non-conventional MR techniques to the clinical management of patients with MS. These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS. In addition, they should provide a foundation for the development of more widespread but rational clinical applications of non-conventional MR-based techniques in studies of MS patients.

Brain↗
PubMed2006

CSF biomarkers in frontotemporal lobar degeneration: relations with clinical characteristics, apolipoprotein E genotype, and neuroimaging.

In order to better understand the large variation in cerebrospinal fluid (CSF) tau and amyloid-beta(1-42) (Abeta42) in frontotemporal lobar degeneration (FTLD), relations between these biomarkers and clinical parameters, neuroimaging characteristics, and apolipoprotein E (ApoE) genotype were studied in 31 patients with FTLD, including 16 patients with the frontal variant and 15 with the temporal variant. CSF tau was highest in FTLD with predominant temporal involvement. In the frontal subgroup, CSF tau level was influenced by the number of ApoE epsilon3 alleles. In the temporal subgroup, CSF tau level was dependent on a combination of CSF Abeta42, age, disease duration, and disease severity. No relation with degree of atrophy or asymmetry on neuroimaging could be established. CSF Abeta42 variability remained unexplained. Future research could study the role of ApoE genotype and Abeta42 in FTLD, as well as establish measures for disease intensity.

Age Factors↗
PubMed2006

Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus.

BACKGROUND: The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. OBJECTIVE: To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. METHODS: In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. RESULTS: The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non-DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. CONCLUSION: The results suggest that non-vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2.

Aged↗