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W M van der Flier

Publications and source records attributed to W M van der Flier.

17 recordsLinked to original sources
PubMed2006

The effect of APOE genotype on clinical phenotype in Alzheimer disease.

The authors classified 100 patients with Alzheimer disease (AD) as presenting with a memory or nonmemory phenotype. APOE genotype was determined. There was an association between APOE-epsilon4 and clinical phenotype (odds ratio = 3.0; 95% CI: 1.2 to 7.8), suggesting that two subtypes of AD can be identified. The typical amnestic phenotype seems to be promoted by the APOE-epsilon4 allele, whereas the atypical nonmemory phenotype occurs in the absence of the APOE-epsilon4 allele.

Alzheimer Disease↗
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

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.

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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.

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PubMed2005

[Alzheimer's disease and treatment of vascular risk factors].

There is increasing evidence that vascular risk factors including hypertension, high cholesterol, hyperhomocysteinaemia and diabetes mellitus are connected to the risk of Alzheimer's disease (AD). The risk of AD may be reduced by the treatment of hypertension prior to onset of cognitive impairment. One small randomised clinical trial has provided some evidence of beneficial effects on cognition of cholesterol-lowering drugs such as the statins in patients with AD. Treatment of hypertension, hyperhomocysteinaemia and diabetes mellitus with the aim of halting the progression of cognitive decline in AD is still under study and results are awaited. For the time being findings from the trials carried out thus far should be interpreted with care due to methodological shortcomings, both in study design and execution. In order to investigate the role of vascular risk factors both in the aetiology and treatment of AD, large prospective randomised trials with long-term follow-up of AD patients who have been diagnosed using revised uniform diagnostic criteria that take the heterogeneity of the disease into account, are necessary.

Alzheimer Disease↗
PubMed2005

[Cognitive disorders appearing before the age of 65 in patients of the Alzheimer Centre of the VU Medical Centre: diagnoses and clinical characteristics].

OBJECTIVE: To obtain a profile of the causes and clinical characteristics of cognitive disorders in patients referred to a memory clinic before the age of 65 years. DESIGN: Retrospective case-note study. METHOD: Data were collected from 127 subjects with objective cognitive disorders who visited the Alzheimer Centre of the VU Medical Centre in Amsterdam, the Netherlands, in the period from 1 January 2001 to 31 December 2003 with an onset of complaints before the age of 65. Besides the diagnoses, we investigated the clinical presentations, the occurrence of cardiovascular risk factors, the family history, and the presence of noncognitive neurological signs. RESULTS: The most common causes of cognitive decline under the age of 65 were Alzheimer's disease (46%) and frontotemporal dementia (23%). Vascular dementia was seen in 5% and dementia with Lewy bodies in 2%; 9% had mild cognitive impairment but no dementia. Hypertension and a positive family history for dementia were each present in 40% of the patients. Non-cognitive neurological abnormalities were found only in cases of non-Alzheimer dementia. During the period under investigation, the number of patients with objective cognitive disorders increased more than did the number without a cognitive disorder. CONCLUSION: Within the population of a memory clinic, Alzheimer's disease was the most frequent cause of cognitive decline under the age of 65, followed by frontotemporal dementia. The distribution differed from causes of dementia at an older age, where vascular dementia had the second place.

Adolescent↗
PubMed2005

Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease.

BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early characteristic of Alzheimer's disease. However, hippocampal atrophy may also occur in other dementias, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia, 13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for repeated measures showed an effect of diagnostic group on hippocampal volume. There was a significant diagnosis by side (left v right) interaction. Both FTLD and Alzheimer's disease showed hippocampal atrophy compared with controls. Results of the visual MTA rating scale confirmed these findings. Within the FTLD subtypes there were marked differences in hippocampal atrophy. Frontotemporal dementia and semantic dementia showed bilateral hippocampal atrophy, and in semantic dementia the left hippocampus was smaller than in Alzheimer's disease. No significant hippocampal atrophy was detected in non-fluent progressive aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD show different patterns of hippocampal atrophy.

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PubMed2005

Magnetization transfer imaging of gray and white matter in mild cognitive impairment and Alzheimer's disease.

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.

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PubMed2005

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study.

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

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PubMed2004

Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD.

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.

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PubMed2001

Dementia with Lewy bodies and AD are not associated with occipital lobe atrophy on MRI.

Dementia with Lewy bodies (DLB) is associated with occipital changes in blood flow and metabolism, but structural changes in this region have not previously been assessed. The authors performed volumetric MRI measurement of the occipital lobe blind to the diagnosis in 23 subjects with DLB, 25 with AD, and 24 age-matched control subjects. There were no significant differences between groups in occipital lobe volume. The authors conclude gross structural changes in the occipital lobe do not occur in patients with mild to moderate DLB or AD.

Aged↗
PubMed2000

Frontal lobe damage and thalamic volume changes.

The aim of this study was to investigate whether frontal lobe damage affects thalamic volume in humans. Ipsilateral and contralateral thalamic areas were measured in 0.5T T1-weighted sagittal magnetic resonance images in 12 patients, first at the time of their surgery for relief of a unilateral frontal lobe brain tumor and at follow-up approximately 2 years later. A 5% decrease in ipsilateral and 4.5% increase in contralateral thalamic area was found over time (F(1,11) = 6.15, p < 0.05). We conclude that unilateral frontal lobe damage results in a decrease in the ipsilateral thalamus and an increase in the contralateral thalamus in humans in vivo. The findings may have implications for the interpretation of the reported changes in thalamic volume in neuropsychiatric diseases.

Adolescent↗
PubMedDate not supplied

Hippocampal sulcus width and cavities: comparison between patients with Alzheimer disease and nondemented elderly subjects.

BACKGROUND AND PURPOSE: The hippocampal fissure is a fetal sulcus that, except for its most medial part (the superficial hippocampal sulcus), is normally obliterated. Hippocampal cavities are residual cysts attributable to lack of hippocampal fissure obliteration. We hypothesized that either hippocampal sulcus enlargement or an increase in number or size of hippocampal cavities could be associated with medial temporal lobe atrophy (MTA) occurring in Alzheimer disease. METHODS: Two observers assessed the maximal hippocampal sulcus width by means of the fimbriosubicular distance at the anterior part of the hippocampal body; as well as the occurrence, number, and size of hippocampal cavities; and the visual rating score of MTA on magnified coronal high-resolution T1-weighted MR images of 21 patients with Alzheimer disease and 15 nondemented elderly controls. RESULTS: Both observers found the maximal hippocampal sulcus width significantly larger in patients with Alzheimer disease than in controls (P < .0001). The interobserver averaged fimbriosubicular distance in patients with Alzheimer disease was 2.84 mm (SD = 0.94), approximately twice that of the corresponding distance in nondemented subjects (1.41 mm; SD, 0.58). Both observers found a significant correlation between the fimbriosubicular distance and MTA score (observer 1, r(s) = 0.71; observer 2, r(s) = 0.74; P < .0001). None of the observers found significant differences between patients with Alzheimer disease and nondemented subjects with respect to occurrence, number, or size of hippocampal cavities, nor did they find a significant correlation between the number or size of hippocampal cavities and MTA. Interobserver agreement ranged from moderate to very good. CONCLUSION: Enlargement of the hippocampal sulcus, assessed by the fimbriosubicular distance, is associated with MTA in Alzheimer disease, but enlargement of the hippocampal cavities is not.

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