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J C van Swieten

Publications and source records attributed to J C van Swieten.

At least 19 recordsLinked to original sources
PubMed2007

Diagnosis and management of early- and late-onset cerebellar ataxia.

Cerebellar ataxias represent a heterogeneous group of neurodegenerative disorders. Two main categories are distinguished: hereditary and sporadic ataxias. Sporadic ataxias may be symptomatic or idiopathic. The clinical classification of hereditary ataxias is nowadays being replaced by an expanding genotype-based classification. A large spectrum of degenerative and metabolic disorders may also present with ataxia early or late in the course of disease. We present a diagnostic algorithm for the adult patient presenting with subacute cerebellar ataxia, based on family history and straightforward clinical characteristics of the patient. Along with the algorithm, an overview of the autosomal dominant, autosomal recessive, X-linked, mitochondrial, symptomatic and idiopathic subtypes of cerebellar ataxia is presented. An appropriate diagnosis is of utmost importance to such considerations as prognosis, genetic counselling and possible therapeutic implications.

Algorithms↗
PubMed2006

Cerebrovascular risk factors do not contribute to genetic variance of cognitive function: the ERF study.

Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.

Adult↗
PubMed2005

Familial aggregation, the PDE4D gene, and ischemic stroke in a genetically isolated population.

OBJECTIVE: The purpose of this investigation was to study the familial aggregation of ischemic stroke and the association between the PDE4D gene and ischemic stroke. METHODS: The study was performed in an isolated population in The Netherlands, where the authors identified 91 patients with ischemic stroke. Ischemic stroke was subclassified in large- and small-vessel infarction. The authors calculated kinship and inbreeding coefficients and genotyped all patients for three single-nucleotide polymorphisms (SNPs) in the PDE4D gene. RESULTS: The proportion of related pairs was higher in patients with ischemic stroke (68.8%) compared with controls (30.7%; p < 0.001). For large-vessel infarction, the proportion of related pairs was higher (71%) compared with small-vessel infarction (62.8%; p < 0.001). Familial aggregation was strongest for patients with early onset (age at onset < 45 years). All stroke groups were significantly more inbred compared with controls. In inbred individuals, the C allele of SNP45 increased the risk of small-vessel infarction 4.8 times (95% CI 1.1 to 22.3) compared with controls (p = 0.04). The T allele of SNP39 increased the risk of small-vessel infarction 6.3 times (95% CI 1.4 to 28.7) compared with controls (p = 0.02). No associations were found for large-vessel stroke. CONCLUSIONS: There was familial aggregation of ischemic stroke and a difference in degree of familial clustering between stroke subtypes. The authors also found that the PDE4D gene is significantly associated with small-vessel infarction in inbred individuals.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Hereditary Pick's disease with the G272V tau mutation shows predominant three-repeat tau pathology.

Frontotemporal dementia and parkinsonism linked to chromosome 17 have been associated with mutations in the microtubule associated protein tau (MAPT or tau) gene. This disorder is characterized by a large spectrum of neuronal and glial tau lesions in different brain regions. Pick bodies were found in a family with hereditary Pick's disease with the G272V mutation and in several families with other tau mutations in exons 9 and 11-13. The biochemical composition of Pick bodies varies between these mutations. Until recently, no detailed biochemical characterization of G272V brain material was done owing to unavailability of fresh frozen brain material. We now report a detailed study using the immunohistochemistry, western blots and electron microscopy of two brains with the G272V mutation that recently became available. Both brains showed severe neuronal loss in the temporal cortex, whereas in the frontal cortex the loss was less; and abundant Pick bodies in the dentate gyrus of the hippocampus, and caudate nucleus. The Pick bodies consisted exclusively of three-repeat (3R) isoforms, as was demonstrated by isoform-specific antibodies and supported by western blot analysis of sarkosyl-insoluble tau. These observations confirm that this family diagnosed with hereditary Pick disease meets all the criteria for this condition, including the presence of Pick bodies that are unphosphorylated at Ser262 and contain twisted filaments with long periodicity consisting only of 3R tau.

Blotting, Western↗
PubMed2004

Familial clustering and genetic risk for dementia in a genetically isolated Dutch population.

Despite advances in elucidating the genetic epidemiology of Alzheimer's disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around 1750. The series of 191 patients ascertained comprised 122 probable Alzheimer's disease patients with late onset and 17 with early onset, and 22 with possible Alzheimer's disease. It further included 10 patients with vascular dementia, nine with Lewy body dementia and six with frontotemporal dementia. All patients, except those with vascular dementia, were more closely related than healthy individuals from the same area. Clustering was strongest for patients with early-onset Alzheimer's disease or Lewy body dementia. Although 14% of late-onset Alzheimer's disease patients had evidence of autosomal dominant disease, consanguinity was found in three late-onset Alzheimer's disease patients, suggesting a recessive or polygenic model underlying the trait. We found no clustering of vascular dementia, implying a difference in genetic risk for late-onset Alzheimer's disease and vascular dementia. Mutations in known genes could not explain the occurrence of dementia, but the population attributable proportion of apolipoprotein E gene (APOE*4) was high (45%) due to a high frequency of APOE*4 carriers. Earlier identified regions on chromosomes 10 and 12, nor the effect of the alpha-2-macroglobulin (A2M) I/D polymorphism on Alzheimer's disease could be confirmed in our study. We did find evidence for association between the A2M D-allele and Lewy body dementia. Our data showed a strong familial clustering of various forms of dementia in this isolated Dutch population. A high percentage of late-onset Alzheimer's disease could be explained by APOE*4, but 55% of its origin is still unknown.

Age of Onset↗
PubMed2004

[Progressive supranuclear palsy; an unusual form of parkinsonism].

Progressive supranuclear palsy is a neurodegenerative disorder accompanied by parkinsonism, disturbances of eye movements, pseudobulbar palsy and often cognitive decline. Onset of disease is usually between 50-70 years of age and mean survival is 5-8 years. The prevalence of PSP has been estimated at around 5 per 100,000, although exact figures for the population of the Netherlands are not yet available. International consensus criteria differentiate between possible, probable and definite PSP; the latter requiring neuropathological confirmation. An extensive differential diagnosis may be made early in the course of the disease, but at a later stage development of the characteristic symptoms will make diagnosis easier. Imaging techniques can lend support to the clinical diagnosis to a limited extent, although they lack sufficient specificity to confirm it. PSP is a 'tauopathy' characterized by aggregates of abnormal tau protein in the basal ganglia and brainstem. Some mutations in the tau gene can cause a clinical and pathological picture similar to that of PSP, although most patients with sporadic and familial PSP do not have tau mutations. Various studies have found a strong association between PSP and a specific tau haplotype (H1 haplotype), but its role in the pathophysiological mechanism of PSP is still unclear and needs further research.

Age Factors↗
PubMed2004

Octapeptide repeat insertions in the prion protein gene and early onset dementia.

OBJECTIVES: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer's disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved. METHODS: Following identification of a two-octapeptide repeat insertion in PRNP, we conducted a meta-analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. RESULTS: We found an increasing number of repeats associated with younger age at onset (p < 0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p < 0.001) when adjusting for age at onset. CONCLUSIONS: Our findings show significant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies.

Age of Onset↗
PubMed2003

Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD.

OBJECTIVE: To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. METHODS: Seven patients with FTD and seven patients with AD were studied (Clinical Dementia Rating: four patients with FTD 0.5, three patients with FTD 1, all patients with AD 1; mean Mini-Mental State Examination score: FTD 28.0 +/- 2.1, AD 23.1 +/- 2.7). Cerebral atrophy on MRI was mild, with no differences between FTD and AD. A parametric working memory task was applied to assess frontal activation as a function of working memory load. RESULTS: The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. CONCLUSIONS: These data on regional functional loss in the frontal cortex in early FTD suggest that fMRI can identify FTD when results on structural MRI are normal.

Aged↗
PubMed2003

A clinical-genetic study of Parkinson's disease in a genetically isolated community.

The role of genetic factors in idiopathic, late-onset Parkinson's disease (PD) remains unclear, in spite of the recent advances in the genetics of early-onset forms of familial parkinsonism. There is increasing interest in using genetically isolated populations to unravel the genetics of complex diseases such as late-onset PD. We have studied genetic and clinical features of 109 patients with parkinsonism from an area comprising a genetically isolated population in the South-West of the Netherlands. Of the 109 patients with ascertained parkinsonism, 41 patients were diagnosed with PD and could be linked to a common founder 14 generations ago. The distribution of ages at onset of PD in the genetically isolated population was significantly bimodal, showing two peaks (one with a mean at age 67 years and another with a mean at 44 years, the former peak being significantly larger than that in a population-based study, the Rotterdam Study). In other clinical features, the only statistically significant difference between early-onset and late-onset PD was a decreased motor and cognitive function in patients with late-onset PD. Involvement of other PD genes including DJ-1, a gene implicated in a kindred with early-onset parkinsonism from the same genetic isolate, was excluded in other PD patients in the population. The finding of a common ancestor in 41 idiopathic-PD patients along with the exclusion of known PD genes and loci suggests the presence of at least one other, yet unknown, susceptibility gene involved in PD in this population.

Adult↗
PubMed2003

DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism.

Four chromosomal loci ( PARK2, PARK6, PARK7, and PARK9) associated with autosomal recessive, early onset parkinsonism are known. We mapped the PARK7 locus to chromosome 1p36 in a large family from a genetically isolated population in the Netherlands, and confirmed this linkage in an Italian family. By positional cloning within the refined PARK7 critical region we recently identified mutations in the DJ-1 gene in the two PARK7-linked families. The function of DJ-1 remains largely unknown, but evidence from genetic studies on the yeast DJ-1 homologue, and biochemical studies in murine and human cell lines, suggests a role for DJ-1 as an antioxidant and/or a molecular chaperone. Elucidating the role of DJ-1 will lead to a better understanding of the pathogenesis of DJ-1-related and common forms of Parkinson's disease.

Chromosomes, Human, Pair 1↗
PubMed2003

Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study.

A retrospective case-control study was carried out on 80 patients with sporadic frontotemporal dementia and 124 age, sex, and surrogate informant matched controls with respect to various medical and environmental risk factors. Head trauma was associated with an odds ratio of 3.3 (95% confidence interval (CI), 1.3 to 8.1). Although recall bias may play a role, the frontal lobes are known to be especially vulnerable to even mild head trauma. Thyroid disease was associated with a 2.5 times increased risk of frontotemporal dementia (95% CI, 0.9 to 7.9), which was not statistically significant (p = 0.09) owing to limited power. As altered thyroid hormone status has been observed before in frontotemporal dementia, future studies will be important to confirm this observation.

Aged↗
PubMed2002

Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7.

Autosomal recessive, early onset parkinsonism (AREP) is genetically heterogeneous. Mutations in the parkin gene (PARK2 locus, chromosome 6q) account for up to 50% of AREP families. The parkin protein displays ubiquitin-ligase activity for different targets, which accumulate in the brain of patients with parkin defect and might cause neurodegeneration. Two new AREP loci (PARK6 and PARK7) have been recently mapped on chromosome 1p and confirmed in independent datasets, suggesting that both might be frequent. The three AREP forms display similar clinical phenotypes. Recruiting new families will help cloning the defective genes at PARK6 and PARK7 loci. This will contribute to unraveling the pathogenesis of AREP, and it is also expected to foster our understanding of molecular events underlying classic Parkinson's disease.

Age of Onset↗
PubMed2001

Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsonism with multiple consanguinity loops in a genetically isolated population. Homozygosity mapping resulted in significant evidence for linkage on chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16 cM. On the basis of several recombination events, the region defining the disease haplotype can be clearly separated, by > or =25 cM, from the more centromeric PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism.

Age of Onset↗
PubMed2001

Reproductive period and risk of dementia in postmenopausal women.

CONTEXT: Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied. OBJECTIVE: To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause. DESIGN AND SETTING: The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. PARTICIPANTS: A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia. MAIN OUTCOME MEASURES: Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause. RESULTS: During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed. CONCLUSION: Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.

Aged↗
PubMed2001

Complex compulsive behaviour in the temporal variant of frontotemporal dementia.

OBJECTIVE: As metabolic and structural changes in frontotemporal-subcortical pathways have been reported in patients with obsessive-compulsive disorders, we investigated the correlation between complex compulsive behaviour (CCB) and the distribution of atrophy in a group of 90 patients with frontotemporal dementia (FTD). METHODS: CCB was defined as complex, intentional, and time consuming repetitive behaviour, which was distinguished from simple compulsive behaviour (SCB), such as verbal and motor repetitions and utilisation behaviour. Cortical atrophy on CT and/or MRI was semi-quantitatively assessed in frontal, temporal, parietal and occipital regions, and the pattern of atrophy was compared between patients with and without CCB or SCB. Linear measures were used to establish the presence of caudate atrophy (bicaudate ratio) and ventricular enlargement (bifrontal ratio). RESULTS: CCB was reported in 18 (21%) and SCB in 53 (61%) FTD patients. Frontotemporal atrophy was present in 64 patients (74%), and predominant temporal atrophy in 23 (26%). The pattern of atrophy was asymmetric in 25 patients (29%). Logistic regression analysis showed that temporal lobe atrophy (p < 0.005), as well as asymmetry of atrophy (p < 0.05) were independently associated with CCB, after adjusting for age at onset, gender, duration of symptoms at the time of imaging, severity of atrophy, and bicaudate and bifrontal ratio. No relationship was found between the presence of SCB and the distribution of atrophy, although patients with SCB tended to have more caudate atrophy (p < 0.1). CONCLUSION: Temporal lobe atrophy appears to mediate CCB in patients with FTD, especially if asymmetry of atrophy is present. Future studies with quantitative and volumetric measurements of the cortical and subcortical structures may further clarify the aetiology of CCB in FTD.

Aged↗
PubMed2001

Molecular analysis of mutant and wild-type tau deposited in the brain affected by the FTDP-17 R406W mutation.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a familial neurological disorder, characterized genetically by autosomal dominant inheritance, clinically by behavioral abnormalities and parkinsonism, and neuropathologically by tauopathy. Linkage analyses of affected families have led to identification of several exonic and intronic mutations in the tau gene. In this study, we analyzed molecular species of tau in the soluble and insoluble fractions of brain affected by the FTDP-17 R406W mutation. Protein chemical analysis and Western blotting using site-specific antibodies indicated that almost equal amounts of wild-type and mutant tau were present in the Sarkosyl-insoluble fraction of the R406W brain. Consistent with this, wild-type and mutant tau colocalized in neurofibrillary tangles in the frontal cortex and hippocampus of the R406W brain. In contrast to soluble R406W tau, which was less phosphorylated than soluble wild-type tau, the Sarkosyl-insoluble mutant tau was highly phosphorylated as well as the insoluble wild-type tau.

Aged↗