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Biomedical subjects

W A van Gool

Publications and source records attributed to W A van Gool.

At least 37 records · Page 2Linked to original sources
PubMed2000

14-3-3 testing in diagnosing Creutzfeldt-Jakob disease: a prospective study in 112 patients.

OBJECTIVE: To study the sensitivity and specificity of 14-3-3 testing in a prospective series of patients suspected of having Creutzfeldt-Jakob disease (CJD). BACKGROUND: The 14-3-3 protein immunoassay on CSF has favorable test characteristics as a premortem diagnostic tool in CJD. However, the 14-3-3 protein is a normal cellular protein expressed in various tissues, and its presence in CSF reflects extensive destruction of brain tissue as in CJD, but also in ischemic stroke and meningoencephalitis. METHODS: 14-3-3 was tested in the CSF of a prospective series of 110 consecutive patients suspected of having CJD. RESULTS: The sensitivity was 97% and the specificity was 87% in this series. False-positive results were mainly caused by stroke and meningoencephalitis. CONCLUSION: The 14-3-3 protein is a highly sensitive and specific marker for CJD when used in the appropriate clinical context.

14-3-3 Proteins↗
PubMed2000

The two faces of Alzheimer's disease.

Correct classification of patients with dementia is pertinent to proper interpretation of research findings. However, the history of Alzheimer's disease (AD) is characterized by a continuing debate on its nosological status. Cerebrovascular pathology, Lewy bodies, or hippocampal sclerosis in combination with neuropathological signs of AD of only limited severity results in a disease that is essentially different from severe, purely degenerative AD. The clinical signs, course of the disease, and pathological correlates in elderly patients suffering from "mixed dementia of the Alzheimer type," may differ from those with "purely degenerative Alzheimer's disease" as encountered in relatively young patients. Both clinicians and researchers have much to gain from a perspective that acknowledges the differences between these subgroups of AD patients. It may provide a more realistic perspective, and it holds promise for new opportunities for prevention and treatment.

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PubMed2000

Neuroinflammation and Alzheimer disease: clinical and therapeutic implications.

In Alzheimer disease brains, the amyloid plaques are closely associated with a locally induced, nonimmune-mediated, chronic inflammatory response without any apparent influx of leukocytes from the blood. The present findings indicate that in cerebral A beta diseases (Alzheimer disease, Down syndrome, hereditary cerebral hemorrhage with amyloidosis-Dutch type), the clinical symptoms are determined to a great extent by the site of inflammatory response. It was found that the formation of the amyloid-microglia complex seems to be a relatively early pathogenic event that precedes the process of severe destruction of the neuropil. The idea that inflammation is implicated in Alzheimer pathology has received support from the epidemiologic studies indicating that the use of anti-inflammatory drugs can prevent or retard the Alzheimer disease process. In this contribution, we review the relationship between inflammation and clinical manifestation and the opportunities for anti-inflammatory treatments in Alzheimer disease.

Alzheimer Disease↗
PubMed1999

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer's disease.

We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer's disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer's disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0. 01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0. 05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer's disease, with a threshold effect of low rCBF and high risk of mortality.

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PubMed1999

Early diagnosis of dementia: which tests are indicated? What are their costs?

Dementia is reversible in a minority of patients, and these should be diagnosed but without subjecting the majority with irreversible disease to an excessive set of investigations. Should a battery of ancillary investigations be performed routinely in dementia? Or can these tests be carried out as clinically indicated? Three arguments are important to answer this question. (a) Reversible dementia is rare: about 1% of cases. (b) If the clinical criteria for diagnosing primary degenerative disease are used consistently, the results of investigations can be predicted with sufficient accuracy, except those of blood tests. (c) Treatment of reversible dementia has the best results in its most frequent causes: depression and drug intoxication; however, treatment of medical and surgical causes of dementia may also be effective. Based on these three considerations, we propose the following guideline in the setting of a memory clinic: to perform blood tests in every patient with dementia, but also to perform other tests, such as electroencephalography (EEG) and computed tomography (CT), as clinically indicated.

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PubMed1999

The diagnostic value of electroencephalography in mild senile Alzheimer's disease.

OBJECTIVE: We investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimer's disease (AD), using the grand total of EEG (GTE) score. METHODS: Forty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study. RESULTS: Frequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%. CONCLUSION: In conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.

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PubMed1998

[Cholinesterase inhibitors for Alzheimer disease: preliminary recommendations for treatment. Dutch Society for Psychiatry, Section of Geriatric Psychiatry].

Several cholinesterase inhibitors have recently become available for Alzheimer's disease. To reach consensus about their relevance and use in daily practice, a meeting with clinical experts was organised by the section of Geriatric Psychiatry of the Dutch Society for Psychiatry. So far, available drugs have only very modest effects on cognitive functioning and clinical impression, compared with placebo. The question whether these effects are clinically relevant cannot be answered yet. Awaiting the results of further studies, it was decided not to use cholinesterase inhibitors on a routine basis but to limit prescription of these drugs to research setting or under well-controlled conditions with regard to diagnosis and evaluation. Furthermore, prescription must be limited to mild or moderately severe dementia caused by 'probable Alzheimer's disease'. Proper evaluation in the individual patient is still an unresolved problem. Therefore, n = I protocols are to be designed. These should include the use of appropriate and standardised instruments measuring cognitive functions, behavioural functions and activities of daily life. The skills and experience required will be available in specialised and multidisciplinary units for dementia. Pharmaceutical treatment for Alzheimer's disease must be integrated with all other available forms of patient care.

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PubMed1998

[Presenilins as a marker of Alzheimer's disease].

Although the sporadic form of Alzheimer's disease is the most common, rare familial variants exist. Approximately 50% of these cases are caused by a mutation in the presenilin genes. Mutations in presinilin genes give rise to Alzheimer's disease in a dominant pattern of inheritance with an early age of onset (< 60 years). Both presenilins (PS-1 and PS-2) are transmembrane proteins localized in the intracellular membranes of the endoplasmatic reticulum and Golgi apparatus. This suggests they play a role in transport or sorting of proteins in the cell. Different lines of evidence directly link presenilin to the formation of beta-amyloid, an important constituent of senile plaques. PS-1 has an essential function during development: mice lacking intact PS-1 are not viable. In addition, structural and functional homologies have been identified between presenilins and Notch signal transduction pathways, which play a role in development. The discovery of the presenilin mutations has provided a new angle to Alzheimer's disease research. Eventually, this will probably greatly contribute to knowledge of the pathogenesis of the disease and in time support the development of novel therapeutic strategies.

Alzheimer Disease↗
PubMed1998

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease.

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.

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PubMed1998

Slowing on quantitative spectral EEG is a marker for rate of subsequent cognitive and functional decline in early Alzheimer disease.

The relation between quantitative spectral electroencephalogram (qEEG) parameters and subsequent rate of cognitive, functional, and behavioral decline in 82 consecutive patients with early probable Alzheimer disease (NINCDS-ADRDA criteria) was examined in a prospective study. The qEEG was performed at initial examination and global cognitive function, activities of daily living, and behavior were assessed at initial evaluation and after a period of 6 months. Using multiple linear regression analysis, higher frontocentral and parieto-occipital theta values, lower parieto-occipital beta values, and lower peak frequency were significantly associated with more decline in global cognitive function over the follow-up period. In addition, lower parieto-occipital beta values were significantly related to more decline in activities of daily living. These associations were independent of demographic (age, sex, and education) and disease characteristics [initial Cambridge Examination for Mental Disorders of the Elderly Cognitive test (CAMCOG) or Mini-Mental State Examination scores, estimated duration of symptoms, estimated prior rate of decline, and dementia severity]. In a separate multiple logistic regression analysis, prediction of rapidly progressive decline, defined as 8 or more points decline in CAMCOG scores (n = 21), could be made with parieto-occipital and frontocentral beta values. The results suggest that slowing on qEEG is a marker for subsequent rate of cognitive and functional decline in mildly demented AD patients, independent of demographic or disease characteristics.

Activities of Daily Living↗
PubMed1998

Familial aggregation in frontotemporal dementia.

OBJECTIVE AND BACKGROUND: Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown. METHODS: We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects. RESULTS: We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9+/-10.6 years) was significantly lower than among affected relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7). CONCLUSION: This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.

Adult↗
PubMed1997

[Cerebral hyperperfusion syndrome following carotid endarterectomy].

Three patients with a severe symptomatic carotid stenosis developed headache, epileptic seizures and focal neurologic deficits several days after carotid endarterectomy. CT of the brain revealed hypodensities, indicative of cerebral oedema with haemorrhagic components. This is caused by cerebral hyperperfusion, a complication after carotid endarterectomy as a result of increased cerebral perfusion on the side of the operated carotid stenosis. Dysfunction of the cerebral autoregulation believed to be the cause of this hyperperfusion. Sometimes these complications are incorrectly attributed to one of the better known types of stroke.

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PubMed1997

[Creutzfeldt-Jakob disease; one year later].

During the last year the knowledge of the transmission of prion diseases has increased. New diagnostic methods were developed: investigation of cerebrospinal fluid for the 14-3-3 protein and tonsillar biopsy to detect protease resistant prion protein. Indirect evidence of a causal relation between new variant Creutzfeldt-Jakob disease (nvCJ) and bovine spongiform encephalopathy (BSE) is accumulating, although epidemiological data do not indicate that the incidence of CJ is increasing.

Adult↗
PubMed1997

Reversible dementia in elderly patients referred to a memory clinic.

Dementia has a reversible cause in some cases, and these should be diagnosed without over-investigating the many patients with irreversible disease. We prospectively studied the prevalence of reversible dementia in a memory clinic, determined the added value of investigations compared with clinical examination and assessed the outcome of treatment of potentially reversible causes by measuring (1) cognition, (2) disability in daily functioning, (3) behavioural changes and (4) caregiver burden. Two hundred patients aged 65 years and over were examined, using the CAMDEX-N. If they were demented, the probable cause was diagnosed clinically and confirmed or excluded by a standard set of investigations, which were done in all patients. Of the patients, 170 (mean age 79.2 years) were demented; 31 were treated for potentially reversible causes. At follow-up after 6 months, no patients showed complete reversal of dementia. Five patients improved on clinical impression, but only one on clinical measurement. Thirty patients were cognitively impaired, but not demented; seven were treated. Judged clinically, three patients improved, but on assessment only one did so; she recovered completely. Blood tests often produced diagnostic results that were not expected clinically, but electroencephalography and computed tomography of the brain did not. None of the investigations had an effect on outcome of dementia after treatment. We conclude that in elderly patients referred to a memory clinic, the prevalence of reversible dementia is of the order of 1%, if outcome after treatment is assessed by a standardized measurement. We recommend blood tests in all patients, to detect not only metabolic causes of dementia but also co-morbidity possibly worsening the dementia. Other investigations can be performed on clinical indication. Clinical evaluation remains the mainstay of diagnosis in dementia.

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PubMed1997

Emerging treatments in dementia.

Dementia is one of the most common organic mental syndromes, usually caused by Alzheimer's disease (AD) or vascular dementia (VD) or both. Regarding AD we review the state or the art of the cholinergic approach and discuss some future options regarding preventive and nonsymptomatic strategies. Therapy for VD will consist mainly in influencing and preventing cerebrovascular pathology, because operational criteria for the diagnosis have only recently been proposed and are being discussed widely. One of the crucial problems here lies in the distinction between VD and AD and the recognition that the two disorders may be coexistent more often than assumed; the role of white matter changes seems to be particularly important. The same goes for the recognition that AD ist not a single entity. The question of heterogeneity may be solved when different therapeutic strategies are found for different subtypes. The focus of future plans should be on preventive strategies combined with an early diagnosis.

Alzheimer Disease↗
PubMed1997

Symptomatic treatment of elderly patients with early Alzheimer's disease at a memory clinic.

It is widely accepted that excess disability (treatable coexisting physical disorders and psychiatric phenomena) is common in demented patients, and should be looked for carefully and treated properly, as it may result in improvement. This idea, however, does not state what investigations should be performed and what kind of improvement can be expected. Therefore, we studied prospectively in elderly outpatients with early Alzheimer's disease the prevalence of excess disability, the results of medication treatment, and the added value of investigations for diagnosis, treatment, and outcome after clinical examination. Outcome was assessed clinically and clinimetrically (using instruments with regard to cognition, disability in daily functioning, behavior, and caregiver burden). Excess disability was present in 66% of patients. Medication treatment was effective with regard to target symptoms, but (partial) reversal of dementia did not occur. Only blood tests produced unexpected results with consequences for treatment and outcome. Positive treatment effects often resulted from clinical examination only. We recommend blood tests in all patients; other investigations can be performed on clinical indication.

Activities of Daily Living↗