Alzheimer Disease: van Buchem MA

Blauw GJ, Bollen EL, van Buchem MA, Westendorp RG. · Section of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands. · Eur Heart J. · Pubmed #11913485 No free full text.

Abstract: The main causes of dementia at old age are Alzheimer's disease and vascular dementia. The clinical presentations of late-onset Alzheimer's disease and vascular dementia can barely be differentiated. This clinical observation is supported by pathological findings. Late-onset dementia should be considered a multifactorial disease, in which both vascular factors and amyloid dispositions contribute to cognitive decline.

Bosma GP, van Buchem MA, Voormolen JH, van Biezen FC, Brouwer OF. · Department of Neurology, Leiden University Medical Centre, The Netherlands. · J Intellect Disabil Res. · Pubmed #10466866 No free full text.

Abstract: Progressive walking difficulties and bladder dysfunction may be attributed to Alzheimer disease or atlanto-axial subluxation in people with Down's syndrome (DS). The present authors describe five patients with DS suffering from the above symptoms as a result of cervical spondylarthrotic myelopathy. Clinical and radiological data were collected from all patients with DS who underwent surgery for cervical spondylarthrotic myelopathy at the Leiden University Medical Centre during the period between 1991 and 1995. Five patients with DS (four males and one female) were identified. Their mean age at diagnosis was 42 years. The main clinical features were weakness of the arms and legs, ataxic gait, hyperreflexia and bilateral Babinski signs. Radiological examination showed spondylarthrosis, compression of the spinal cord and myelomalacia. The mean delay in diagnosis was 3 years. All five individuals showed clinical stabilization after laminectomy. Cervical spondylarthrotic myelopathy seems a rather frequent disorder in DS, occurring at a relatively young age. Early diagnosis may prevent irreversible neurological deficits.

de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, van der Grond J. · Department of Radiology, University Medical Center, Leiden, The Netherlands. · Brain. · Pubmed #19022861 links to  free full text

Abstract: 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 Alzheimer's disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimer's 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 Alzheimer's disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIB's Integrated Registration and Segmentation Tool (FIRST)--algorithm FMRIB's 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 Alzheimer's disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimer's 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 Alzheimer's disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimer's disease.

van der Hiele K, Bollen EL, Vein AA, Reijntjes RH, Westendorp RG, van Buchem MA, Middelkoop HA, van Dijk JG. · Department of Neurology (Neuropsychology section), Leiden University Medical Center, Leiden, The Netherlands. · J Clin Neurophysiol. · Pubmed #18340274 No free full text.

Abstract: This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8-13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the "cognition only" model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.

Ferrarini L, Palm WM, Olofsen H, van der Landen R, van Buchem MA, Reiber JH, Admiraal-Behloul F. · LKEB-Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. · Magn Reson Med. · Pubmed #18228600 No free full text.

Abstract: The aim of this work was to identify ventricular shape-based biomarkers in MR images to discriminate between patients with Alzheimer's disease (AD) and healthy elderly. Clinical MR images were collected for 58 patients and 28 age-matched healthy controls. After normalizing all the images the ventricular cerebrospinal fluid was semiautomatically extracted for each subject and an innovative technique for fully automatic shape modeling was applied to generate comparable meshes of all ventricles. The search for potential biomarkers was carried out with repeated permutation tests: results highlighted well-defined areas of the ventricular surface being discriminating features for AD: the left inferior medial temporal horn, the right medial temporal horn (superior and inferior), and the areas close to the left anterior part of the corpus callosum and the head of the right caudate nucleus. The biomarkers were then used as features to build an intelligent machine for AD detection: a Support Vector Machine was trained on AD and healthy subjects and subsequently tested with leave-1-out experiments and validation tests on previously unseen cases. The results showed a sensitivity of 76% for AD, with an overall accuracy of 84%, proving that suitable biomarkers for AD can be detected in clinical MR images.

Ferrarini L, Palm WM, Olofsen H, van der Landen R, Jan Blauw G, Westendorp RG, Bollen EL, Middelkoop HA, Reiber JH, van Buchem MA, Admiraal-Behloul F. · Division of Image Processing, Leiden University Medical Center, Leiden, The Netherlands. · Neuroimage. · Pubmed #18160312 No free full text.

Abstract: In this work, we aimed at correlating focal atrophy in periventricular structures with cognitive function, in the spectrum from healthy subjects to severe Alzheimer disease: 28 subjects with normal cognition and 84 patients presenting various degrees of cognitive impairment were included in the study. The cognitive level of each subject was assessed with the Mini-Mental State Examination (MMSE). Atrophy in periventricular structures was inferred by modeling and analyzing local shape variations of brain ventricles: for a given subject, we distinguished between the severity of atrophy, estimated as local enlargement (in mm) of the ventricular surface relative to an average normal subject, and the extent of atrophy, defined as the percentage of the ventricular surface (global or per anatomical region) significantly different from an average control. Linear regression across subjects was performed to evaluate the correlation between atrophy and MMSE score. The severity of atrophy showed good correlation with MMSE score in the left thalamus, the left temporal horn, the left corona radiata, and the right caudate nuclei. The extent of atrophy showed no significant correlations. In conclusion, the MMSE scores correlate with localized depth of atrophy in well-defined periventricular structures.

van Es AC, van der Flier WM, Admiraal-Behloul F, Olofsen H, Bollen EL, Middelkoop HA, Weverling-Rijnsburger AW, van der Grond J, Westendorp RG, van Buchem MA. · Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. · AJNR Am J Neuroradiol. · Pubmed #17925378 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline. MATERIALS AND METHODS: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage. RESULTS: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition. CONCLUSION: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.

van der Hiele K, Vein AA, Reijntjes RH, Westendorp RG, Bollen EL, van Buchem MA, van Dijk JG, Middelkoop HA. · Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. · Clin Neurophysiol. · Pubmed #17604688 No free full text.

Abstract: OBJECTIVE: To investigate relations between EEG measures and performance on tests of global cognition, memory, language and executive functioning. METHODS: Twenty-two controls, 18 patients with mild cognitive impairment (MCI) and 16 with probable Alzheimer's disease (AD) underwent neuropsychological and EEG investigations. We used the following EEG measures: theta relative power during eyes closed, alpha reactivity during memory activation (i.e. the percentual decrease in alpha power as compared to eyes closed) and alpha coherence during eyes closed and memory activation. RESULTS: Theta relative power was increased in AD patients as compared with controls (p<0.001) and MCI patients (p<0.01) and related to decreased performance in all cognitive domains. Alpha reactivity was decreased in AD patients as compared with controls (p<0.005) and related to decreased performance on tests of global cognition, memory and executive functioning. Alpha coherence did not differ between groups and was unrelated to cognition. CONCLUSIONS: EEG power measures were associated with decreased performance on tests of global cognition, memory, language and executive functioning, while coherence measures were not. SIGNIFICANCE: The EEG yielded several power measures related to cognitive functions. These EEG power measures might prove useful in prospective studies aimed at predicting longitudinal cognitive decline and dementia.

Ferrarini L, Olofsen H, Palm WM, van Buchem MA, Reiber JH, Admiraal-Behloul F. · LKEB - Division of Image Processing, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. · Med Image Anal. · Pubmed #17478119 No free full text.

Abstract: This paper presents a new framework for shape modeling and analysis, rooted in the pattern recognition theory and based on artificial neural networks. Growing and adaptive meshes (GAMEs) are introduced: GAMEs combine the self-organizing networks which grow when require (SONGWR) algorithm and the Kohonen's self-organizing maps (SOMs) in order to build a mesh representation of a given shape and adapt it to instances of similar shapes. The modeling of a surface is seen as an unsupervised clustering problem, and tackled by using SONGWR (topology-learning phase). The point correspondence between point distribution models is granted by adapting the original model to other instances: the adaptation is seen as a classification task and performed accordingly to SOMs (topology-preserving phase). We thoroughly evaluated our method on challenging synthetic datasets, with different levels of noise and shape variations. Finally, we describe its application to the analysis of a challenging medical dataset. Our method proved to be reproducible, robust to noise, and capable of capturing real variations within and between groups of shapes.

van der Hiele K, Vein AA, van der Welle A, van der Grond J, Westendorp RG, Bollen EL, van Buchem MA, van Dijk JG, Middelkoop HA. · Department of Neurology, Neuropsychology and Clinical Neurophysiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. · Neurobiol Aging. · Pubmed #16854500 No free full text.

Abstract: OBJECTIVE: To investigate whether cognitive function in the spectrum of normal aging to Alzheimer's disease is better reflected in MRI or EEG measures, or a combination of both. METHODS: Cognitive functions were tested in 33 elderly subjects: 10 with probable Alzheimer's 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. RESULTS: The 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. CONCLUSION: EEG and MRI are each associated with different aspects of cognitive function and complement each other in their relations to psychomotor speed.

Ferrarini L, Palm WM, Olofsen H, van Buchem MA, Reiber JH, Admiraal-Behloul F. · Division of Image processing, Leiden University Medical Center, Leiden, The Netherlands. · Neuroimage. · Pubmed #16839779 No free full text.

Abstract: The brain ventricles are surrounded by gray and white matter structures that are often affected in dementia in general and Alzheimer's disease (AD) in particular. Any change of volume or shape occurring in these structures must affect the volume and shape of the ventricles. It is well known that ventricular volume is significantly higher in AD patients compared to age-matched healthy subjects. However, the large overlap between the two volume distributions makes the measurement unsuitable as a biomarker of the disease. The purpose of this work was to assess whether local shape differences of the ventricles can be detected when comparing AD patients and controls. In this work, we captured the ventricle's shape and shape variations of 29 AD subjects and 25 age-matched controls, using a fully automatic shape modeling technique. By applying permutation tests on every single node of a mesh representation of the shapes, we identified local areas with significant differences. About 22% of an average surface of the ventricles presented significant difference (P < 0.05) ( approximately 14% of the left against approximately 7% of the right side). We found out that in patients with Alzheimer disease, not only the lateral horns were significantly affected, but also the areas adjacent to the anterior corpus callosum, the splenium of the corpus callosum, the amygdala, the thalamus, the tale of the caudate nuclei (especially the left one), and the head of the left caudate nucleus.

van Es AC, van der Flier WM, Admiraal-Behloul F, Olofsen H, Bollen EL, Middelkoop HA, Weverling-Rijnsburger AW, Westendorp RG, van Buchem MA. · Department of Radiology, C2-S, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. <> · Neurobiol Aging. · Pubmed #16290268 No free full text.

Abstract: OBJECTIVE: To assess whether structural brain damage as detected by magnetization transfer imaging (MTI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is located in the gray matter (GM) and/or the white matter (WM). METHODS: Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive function participated in this study. GM and WM segmentations were generated from dual fast spin-echo MR images. These masks were co-registrated to MT images for volumetric MTI-analysis of the GM and WM. RESULTS: AD patients had a lower GM volume than controls. Both MCI and AD patients had more structural brain damage in both GM and WM than subjects with normal cognition. Cerebral lesion load in both GM and WM was associated with the degree of cognitive impairment. CONCLUSION: Using MTI, structural brain changes that are related to cognitive impairment could be demonstrated in both GM and WM of patients with AD and MCI. These results suggest that cerebral changes are present in GM and WM even before patients are clinically demented.

van der Flier WM, van der Vlies AE, Weverling-Rijnsburger AW, de Boer NL, Admiraal-Behloul F, Bollen EL, Westendorp RG, van Buchem MA, Middelkoop HA. · Department of Neurology and Alzheimer Center, VU Medical Center, The Netherlands. · Int J Geriatr Psychiatry. · Pubmed #16250078 No free full text.

Abstract: OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.

van der Flier WM, Middelkoop HA, Weverling-Rijnsburger AW, Admiraal-Behloul F, Bollen EL, Westendorp RG, van Buchem MA. · Department of Neurology and Alzheimer Center, VU Medical Center, Leiden, The Netherlands. · Dement Geriatr Cogn Disord. · Pubmed #15942197 No free full text.

Abstract: OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.

van der Flier WM, Middelkoop HA, Weverling-Rijnsburger AW, Admiraal-Behloul F, Spilt A, Bollen EL, Westendorp RG, van Buchem MA. · Department of Neurology, Leiden University Medical Center, The Netherlands. · Neurology. · Pubmed #15159496 No free full text.

Abstract: The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.

van Straaten EC, Scheltens P, Knol DL, van Buchem MA, van Dijk EJ, Hofman PA, Karas G, Kjartansson O, de Leeuw FE, Prins ND, Schmidt R, Visser MC, Weinstein HC, Barkhof F. · Department of Neurology and Alzheimer Center, VU Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, Netherlands. · Stroke. · Pubmed #12855825 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

van der Flier WM, van den Heuvel DM, Weverling-Rijnsburger AW, Bollen EL, Westendorp RG, van Buchem MA, Middelkoop HA. · Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. · Ann Neurol. · Pubmed #12112048 No free full text.

Abstract: The purpose of this study was to assess whether structural brain damage as detected by volumetric magnetization transfer imaging (MTI) is present in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and, if so, whether these abnormalities are global in character or restricted to the temporal lobe. Volumetric MTI analysis of the whole brain and temporal and frontal lobes was performed in 25 patients with probable AD, in 13 patients with MCI, and in 28 controls. Magnetization transfer ratio (MTR) histograms were produced, from which we derived measures for structural brain damage and atrophy. The peak heights of the MTR histograms of MCI and AD patients were lower than those of controls for the whole brain and temporal and frontal lobes, reflecting structural brain damage. AD patients had more atrophy than controls in all regions that were studied. MCI patients differed from controls for temporal lobe atrophy only. Volumetric MTI demonstrates structural changes that are related to cognitive decline in large parts of the brain of AD patients. Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented.

van der Flier WM, van Buchem MA, van Buchem HA. · No affiliation provided · Neurology. · Pubmed #12743260 No free full text.

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