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Biomedical subjects

W A van Gool

Publications and source records attributed to W A van Gool.

At least 19 recordsLinked to original sources
PubMed2006

The significance of neuroinflammation in understanding Alzheimer's disease.

The interest of scientists in the involvement of inflammation-related mechanisms in the pathogenesis of Alzheimer's disease (AD) goes back to the work of one of the pioneers of the study of this disease. About hundred years ago Oskar Fischer stated that the crucial step in the plaque formation is the extracellular deposition of a foreign substance that provokes an inflammatory reaction followed by a regenerative response of the surrounding nerve fibers. Eighty years later immunohistochemical studies revealed that amyloid plaques are indeed co-localized with a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) and clusters of activated microglia. These findings have led to the view that the amyloid plaque is the nidus of a non-immune mediated chronic inflammatory response locally induced by fibrillar A beta deposits. Recent neuropathological studies show a close relationship between fibrillar A beta deposits, inflammation and neuroregeneration in relatively early stages of AD pathology preceding late AD stages characterized by extensive tau-related neurofibrillary changes. In the present work we will review the role of inflammation in the early stage of AD pathology and particularly the role of inflammation in A beta metabolism and deposition. We also discuss the possibilities of inflammation-based therapeutic strategies in AD.

Alzheimer Disease↗
PubMed2006

[The practice guideline 'Diagnosis and pharmaceutical treatment of dementia'].

The practice guideline 'Diagnosis and pharmaceutical treatment of dementia' emphasizes that a nosological diagnosis should be made and that it is important to assess the extent of need for care. The guideline recommends the use of diagnostic criteria for the various conditions that can cause dementia. With respect to ancillary investigations, the burden to the patient should be weighed against the benefits of increasing diagnostic confidence. Observation of the course of the disease, laboratory and cerebrospinal-fluid investigations, neuropsychological and EEG examinations, and neuroimaging all increase diagnostic confidence. Treatment with a cholinesterase inhibitor or memantine should always be embedded in a comprehensive-treatment protocol that includes explicit discussion of treatment goals and expectations at baseline, in combination with criteria for starting and stopping treatment. Guidelines for evaluating the effects of treatment with cholinesterase inhibitors or memantine are specified. If psychosis, depression or behavioural disturbances occur in patients with dementia, antidepressants, antipsychotics or anticonvulsants may be indicated.

Antipsychotic Agents↗
PubMed2006

[Cholinesterase inhibitors in dementia: the precarious balance between efficacy and safety].

Cholinesterase inhibitors are widely prescribed in patients with Alzheimer's disease. Recently it has become clear that using these medications increases the risk of serious adverse events like cardiac arrhythmias, and some studies report a much-increased mortality in the treatment group on comparison with the placebo group. In the light of the at best, modest, treatment effects, we advocate that the safety of cholinesterase inhibitors should be the subject of continuing, intense scrutiny. Efforts should be made to delineate the profile of a true 'cholinergic deficiency syndrome', in order to be able to prescribe these medications to a group of patients in whom the benefits outweigh the risks.

Alzheimer Disease↗
PubMed2006

The association of neuroleptic sensitivity in Lewy body disease with a false positive clinical diagnosis of Creutzfeldt-Jakob disease.

BACKGROUND: Dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) share clinical features like cognitive decline, motor disturbances en psychiatric symptoms. Overlapping symptoms may cause physicians to mistake DLB for CJD. METHODS: Clinical data of 12 patients with autopsy-confirmed DLB who had been clinically suspected to suffer from CJD were analysed to investigate possible clinical features which led to misdiagnosis. RESULTS: There was an association in time between administering neuroleptics and rapid clinical deterioration in 8 out of 9 patients. CONCLUSION: It is suggested that the neuroleptic sensitivity in LBD fuelled the misdiagnosis of CJD in the presented series. Diagnostic confusion between CJD and DLB may have important clinical consequences and may lead to treatment restrictions.

Adult↗
PubMed2004

[The practice guideline 'Dementia' (second revision) from the Dutch College of General Practitioners; a response from the perspective of neurology].

The revised version of the practice guideline 'Dementia' from the Dutch College of General Practitioners provides a sound and comprehensive overview, and a practical guideline especially for the period following the diagnostic evaluation. The advice on the issues of whether to refer patients and whether to start symptomatic drug treatment is stated in rather general terms. Therefore, for most general practitioners it will still be difficult to decide how best to act on these issues. The fact that the cognitive examination is treated as part of the history taking will, most probably, negatively affect the quality of the diagnostic evaluation.

Dementia↗
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↗
PubMed2003

Neuroinflammatory perspectives on the two faces of Alzheimer's disease.

The amyloid plaques in Alzheimer's disease (AD) brains are co-localized with a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) and clusters of activated microglia. The present data suggest that Abeta deposits in AD brains are closely associated with a locally induced, non-immune mediated, chronic inflammatory response. Clinicopathological and neuroradiological studies show that activation of microglia is a relatively early pathogenic event that precedes the process of neuropil destruction in AD. Epidemiological studies indicate that polymorphisms of certain cytokines and acute-phase proteins that are colocalized with Abeta plaques, are genetic risk factors of AD. Epidemiological studies have also shown that the use of classical nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent the risk of AD but clinical trials with anti-inflammatory drugs in AD patients were negative. These findings indicate that anti-inflammatory agents can be helpful in the prevention but not in the treatment of AD. So, pathological, genetic and therapeutic studies suggest that inflammatory mechanisms are most likely involved in the early steps of the pathological cascade. In the autosomal dominant inherited forms of AD the primary factor is the increased production of Abeta1-42 resulting into fibrillar Abeta deposition that elicits a brain inflammatory response. The etiology of the sporadic forms is yet unknown but this subtype is considered to be heterogeneous and multifactorial in its pathogenesis. Here we review the evidence that inflammation related events could be a critical etiological factor in certain forms of the sporadic AD.

Acute-Phase Reaction↗
PubMed2003

[Cholinergic deficiency syndrome as an indicator for the cholinesterase inhibitors].

Cholinesterase inhibitors are licensed for the treatment of dementia in Alzheimer's disease. In clinical practice, these drugs have little effect on the cognitive symptoms of dementia. Several studies report a beneficial effect of cholinesterase inhibitors on neuropsychiatric symptoms. We hypothesise that symptoms such as the impairment of attention and concentration, anxiety, restlessness and hallucinations, delineate a specific central cholinergic deficiency syndrome. It is postulated that this syndrome crosses boundaries of nosological entities and occurs in various neurodegenerative diseases. Symptoms resulting from cholinergic deficiency might be a much better target for treatment than cognitive deficits.

Acetylcholinesterase↗
PubMed2003

[Memantine for the treatment of dementia].

Problems in the Netherlands with respect to the reimbursement of memantine have led the patient organization 'Alzheimer Nederland' to establish an emergency fund. Several trials have documented the limited, but consistent beneficial effects of memantine in severely demented patients. It is not clear which subgroup of patients might benefit the most. The drug seems to have dopamimetic and antidepressant effects which might explain its overall effect. The publicity surrounding memantine contributes to an atmosphere in which patients and care providers have to explain why they are not yet using 'anti-dementia drugs'. This should be avoided. Patients can expect to gain more benefit from ongoing, thorough and independent investigations than from hastily established emergency funds to finance the use of a drug with a limited and poorly defined efficacy.

Dementia↗
PubMed2003

Anti-inflammatory therapy in Alzheimer's disease: is hope still alive?

Based on observations from neuropathology, epidemiology, and in vitro and animal experiments, the inflammatory component of Alzheimer's disease (AD) has been considered a compelling target for therapeutic intervention. However, a summary of all published trial reports to date suggests that AD patients do not benefit from treatment with anti-inflammatory drugs. In this brief review, we try to reconcile these sobering trial results with recent observations from basic research and epidemiology that continue to strengthen the idea that inflammatory mechanisms play an important role in the pathogenesis of AD. We review the possibilities that (1) not all components of the inflammatory response in AD are detrimental, (2) beneficial effects of anti-inflammatory drugs may not be mediated by inflammatory pathways, and (3) the timing of the intervention should be in the earliest stages of the pathogenesis of AD, perhaps even before the first symptoms emerge. We conclude that studies on primary prevention of AD are the logical next step in testing the inflammatory hypothesis of AD.

Alzheimer Disease↗
PubMed2002

[Novel therapeutic approach to amyloidosis: no implications as yet for patients with Alzheimer's disease].

Many disorders, such as Alzheimer's disease and diabetes, are characterised by the misfolding and aggregation of proteins. Pepys et al. described a new approach of destabilizing these aggregates by removing an associated protein, serum amyloid P. This offers opportunities for treating amyloidosis and possibly other protein folding diseases. Understanding the mechanism of this unique disease process and the different elements involved is necessary for future drug development.

Alzheimer Disease↗
PubMed2002

[Creutzfeldt-Jakob disease: diagnosis, incidence, prevention and treatment].

Creutzfeldt-Jakob disease (CJD) is a rare, neurodegenerative disorder belonging to the spongiform encephalopathies. A variant form (vCJD) is most likely the result of infection with the agent that causes bovine spongiform encephalopathy (BSE). Diagnostic information can be obtained by EEG, testing cerebrospinal fluid for the presence of the 14-3-3 protein, MRI, brain biopsy, tonsil biopsy, and postmortem brain examination. Some tests, such as MRI and postmortem brain examination, can be used to distinguish between CJD and vCJD. Pathological prions in a tonsil biopsy are only found with vCJD. In the Netherlands, there are four known cases of iatrogenic CJD. On the basis of certain exposure to BSE via the food chain, cases of vCJD are also to be expected. Chloropromazine and mepacrine are known to inhibit the formation of pathological prion conformations, but clinical trials have not yet been carried out.

Animals↗
PubMed2002

[Rivastigmine for Alzheimer disease; evaluation of preliminary results and of structured assessment of efficacy].

OBJECTIVE: Evaluation of the initial experiences with rivastigmine in Alzheimer's disease. DESIGN: Retrospective. METHOD: Data were collected from patients with Alzheimer's disease who were treated with rivastigmine between 1 October 1998-30 November 1999 at the Memory Disorders Outpatients Clinic at the Academic Medical Centre or the Slotervaart Hospital, both in Amsterdam, the Netherlands. Before, and 6 months after treatment, the course of the disease was evaluated using clinimetric scales relating to cognitive functions, behavioural abnormalities and instrumental daily functions. The treatment results were considered to be 'favourable' if they corresponded with a disease course seen in less than 10% of untreated Alzheimer patients. RESULTS: During the study period, 53 patients were treated, 36 women and 17 men, with a mean age of 77 years (range: 57-89). Follow-up data were incomplete for four patients. Of the remaining patients, 27 (55%; 95% CI: 40-69) withdrew from treatment during the first 6 months, mainly because of gastrointestinal side-effects. Of the other 22 patients (45%; 31-60) 18 continued with rivastigmine treatment (18/49 = 37%; 23-52), and in three of these patients the disease course was favourable (3/49 = 6%; 1-17). CONCLUSION: In daily practice, over 50% of the patients were unable to tolerate rivastigmine. Structured evaluation of treatment efficacy was feasible in this population. Treatment with rivastigmine seemed to be beneficial in a small proportion of the patients.

Activities of Daily Living↗
PubMed2001

[Clinical algorithm for cerebrospinal fluid test of 14-3-3 protein in diagnosis of Creutzfeldt-Jacob disease].

OBJECTIVE: To study whether an algorithm that includes additional diagnostic information could increase the specificity of the 14-3-3 protein testing in patients suspected to suffer from Creutzfeldt-Jakob disease (CJD). DESIGN: The development of a diagnostic algorithm. METHOD: The 14-3-3 protein was tested in the cerebrospinal fluid from 69 consecutive patients suspected of having CJD. On the basis of a former study and literature research, a diagnostic algorithm was constructed, which restricted the indication for performing the 14-3-3 protein test. RESULTS: By taking into consideration the findings of neuroimaging and routine cerebrospinal fluid examination prior to 14-3-3 testing, the specificity increased to 97% (95%-CI: 85.5-99.9) thus changing the prior probability of having CJD of 35% to a posterior probability of 75-100%, in the case of a positive test result. CONCLUSION: Determining the presence of 14-3-3 protein is a highly sensitive and specific marker for sporadic CJD when used in combination with imaging and cerebrospinal fluid examination.

14-3-3 Proteins↗
PubMed2001

[Evaluation of the therapeutic effects in individual patients with Alzheimer disease].

Rivastigmine was recently licensed for treatment of Alzheimer's disease on the basis of large double-blind placebo-controlled clinical trials. However, it is difficult to determine the clinical relevance for individual patients from the results of this type of clinical trial. With the help of standardised measurements in individual patients the clinical relevance can be better established. In order to avoid extra burden on patients, caregivers and doctors, these measurements should be simple. A combination of three clinimetrical scales for cognition, ability to perform daily activities and behaviour, which takes about 15 min to complete, appears to be efficient. Comparison of these data with data from a group of untreated Alzheimer's patients can give an impression of the efficacy of the medication. With the use of goal-attainment scaling, measurements can be individualised even more. This approach allows the clinician, in consultation with the caregiver and the patient, to make an informed decision about whether or not to continue treatment.

Activities of Daily Living↗
PubMed2001

The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands.

Creutzfeldt-Jakob disease (CJD) can be transmitted through human growth hormone or gonadotrophin administration, dura mater or cornea transplantation, depth EEG monitoring and the use of contaminated neurosurgical instruments. We describe the first two dura mater associated CJD cases in the Netherlands. Ten and fourteen years before the onset of symptoms both patients received a Lyodura implantation. Findings are discussed in light of the growing epidemic of CJD among dura mater recipients.

Adult↗
PubMed2000

A new mutation in the prion protein gene: a patient with dementia and white matter changes.

The authors describe the clinical characteristics, MRI abnormalities, and molecular findings in a patient with a novel variant of a two-octarepeat insertion mutation in the prion protein gene. This patient presented with moderately progressive dementia of presenile onset and gait ataxia. MRI showed extensive cortical atrophy and white matter abnormalities. The mutation consists of a two-octarepeat insertion mutation and irregularities in the nucleotide sequence of the octarepeat region.

Adult↗