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Biomedical subjects

G J Walstra

Publications and source records attributed to G J Walstra.

14 recordsLinked to original sources

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.

Aged

[Several patients with memory disorders].

In three patients, referred to a memory clinic because of memory impairment, three different types of memory dysfunction were observed: a deficit in encoding of new episodic memories, a relatively pure loss of semantic memory and an impairment in retrieval of stored information. These patients were diagnosed as suffering from Alzheimer's disease, semantic dementia and frontotemporal dementia respectively. The diagnosis was essential in determining the individual management strategy.

Adult

[Reversible dementia due to valproic acid therapy].

A progressive dementia syndrome (DSM IV) with frontal-subcortical features developed in a 72-year-old woman during valproate therapy (Depakine). Discontinuation of valproate resulted in complete recovery. Drugs are a common cause of reversible dementia. The association of dementia with valproate therapy is rare. Features of a subcortical dementia are indicative of a reversible cause. In addition, the possible role of drugs should always be considered in patients with cognitive decline.

Aged

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.

Aged

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

Dementia and subnormal levels of vitamin B12: effects of replacement therapy on dementia.

Routine determination of serum vitamin B12 levels is generally recommended as part of the screening of demented patients, based on the notion that vitamin B12 deficiency is one of the causes of reversible dementia. We studied the effects of vitamin B12 replacement therapy in a prospective longitudinal study at a memory clinic, with special emphasis on assessment of severity of dementia: not only cognitive deterioration, but also disability in the activities of daily life, behavioural problems, and the burden experienced by the caregiver were examined using instruments of proven validity. In a series of 170 consecutive patients with dementia, subnormal serum vitamin B12 levels were found in 26 cases (15%); all but one fulfilled diagnostic criteria for possible Alzheimer's disease. Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months. When the size and pattern of individual change scores, and the mean change scores on all instruments were taken into account, functioning after replacement therapy was not improved. When change scores of treated patients were compared with those of patients with Alzheimer's disease (n = 69), vitamin B12 replacement did not result in slowing of the progression of dementia. Contrary to widely accepted beliefs, subnormal serum vitamin B12 levels are not a (quantitatively) important cause of reversible dementia.

Aged

Concentrations of amyloid beta protein in cerebrospinal fluid of patients with Alzheimer's disease.

Deposition of fibrillar amyloid beta protein (A beta) is increased in brains of patients with Alzheimer's disease. Concentrations of A beta were measured in cerebrospinal fluid with an enzyme-linked immunosorbent assay in 10 neurological patients free from neurodegenerative disease, 28 patients with Parkinson's disease, and 18 patients with probable Alzheimer's disease. Levels of A beta in cerebrospinal fluid were not significantly different among these groups. This observation suggests that concentrations of soluble A beta in cerebrospinal fluid as measured in this study do not reflect the amount of fibrillar, aggregated A beta in the brain of patients with Alzheimer's disease.

Aged

Diagnosing Alzheimer's disease in elderly, mildly demented patients: the impact of routine single photon emission computed tomography.

Based on the observation of bilateral temporoparietal hypoperfusion in Alzheimer's disease (AD), single photon emission computed tomography (SPECT) is advocated by some as a powerful diagnostic tool in the evaluation of demented patients. We studied whether routine brain SPECT in elderly, mildly demented outpatients increases the a priori diagnostic sensitivity and specificity of a careful clinical examination. 99mTc-HMPAO SPECT imaging was performed in 110 patients for a first evaluation for dementia. A semiquantitative measure of temporoparietal (TP) perfusion was calculated as the ratio of the activity in the temporoparietal cortex to activity in the cerebellum. A diagnosis of probable AD according to the McKhann criteria was made in 68 patients (mean age of 79.3 years) based on the results of a clinical examination, ancillary investigations and a 6-month follow-up. TP perfusion was significantly lower in AD patients than in 18 age-matched, non-demented controls. However, at a specificity of 89%, sensitivity was only 43% for detecting probable AD. The clinicians judged that SPECT had contributed to the final diagnosis in only 8% of the demented patients investigated. Routine brain SPECT in elderly, mildly demented outpatients does not contribute substantially to diagnostic accuracy after a careful clinical examination using current diagnostic criteria. Clinical guidelines have to be developed for the use of SPECT in patients with (suspected) dementia.

Aged

[An outpatient clinic for memory disorders; initial experiences].

The department of neurology of the Academisch Medisch Centrum started an outpatient memory clinic in 1987 for patients aged 65 and older. Its specific aims are: assessment of elderly patients with memory problems, treatment where appropriate, and advice; clinical research; teaching and training. The clinic has run full-time since 1990. The approach is multidisciplinary. We describe our findings in the first 75 patients who were referred by their general practitioners because of forgetfulness or possible dementia: 72 of them had a complete investigation; 30 patients were not demented; three could be reassured because their performance was within normal limits. Four patients were depressed and they improved on therapy. Forty-two patients were demented. All had a CT scan and comprehensive blood tests but a curable cause for the dementia syndrome was never identified. This result was expected on account of the probably low frequency of 'reversible' causes and patient selection. Secondary prevention was important when a vascular component contributed to the pathogenesis of the mental deterioration (n = 6). Even when no curable condition was found, clarity about diagnosis and prognosis was important not only to the relatives but also to the general practitioner in planning the future management of the patient. Fifty-five of the 72 patients were older than 65 years which means that we do see the patients we are particularly interested in. The clinic offers facilities for clinical research. In the project 'Diagnostiek bij dementiesyndroom' (Diagnostics in dementia syndrome) we investigate the utility of ancillary investigations in relation to the outcome in demented patients.

Aged

[CAMDEX-N: the Dutch version of the Cambridge Examination for Mental Disorders of the Elderly with automatic data processing].

In the study of dementia four distinct categories of instruments can be distinguished: instruments to examine cognitive dysfunction, to measure the severity of dementia, to assess disturbances in daily behaviour, and instruments to make a differential diagnosis of dementia. The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), published in 1988, incorporates these four categories in a single comprehensive interview schedule. Items related to the diagnosis of clouded/delirious state, depression and other psychiatric symptoms are also included. The Dutch version (CAMDEX-N) and accompanying software for data analysis and for scientific research were developed. Items were added to the section on physical and neurological examination, and to the section on ancillary investigations. The software can be adapted to future developments in dementia research.

Aged

Determinants of global clinical change assessment in patients with early Alzheimer's disease.

Global clinical impression (GCI) of change is assumed to integrate aspects of both cognitive and noncognitive functioning. We evaluated 140 consecutive patients with probable (n = 90) and possible (n = 50) early Alzheimer's disease at baseline and after 6 months with measurements of global cognitive function (CAMCOG), behavior, activities of daily living, and burden of the caregiver. After 6 months, both the clinician (GCI-clin) and the caregiver (GCI-care) rated clinical change on a 3-point scale (worse, no change, improved). Data were analyzed with multiple polychotomous logistic regression, adjusted for age and sex. Change in global cognitive function and GCI-care were significantly and independently related to GCI-clin, while changes in activities of daily living and in behavior were significantly and independently associated with GCI-care. The findings suggest a double dissociation. Change in cognition appears to be the major determinant of the clinician's global impression but not change in behavioral and functional parameters, while global impression of the caregiver is primarily based on change in behavioral and functional measures but not on change in cognition.

Activities of Daily Living

Predicting survival in patients with early Alzheimer's disease.

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer's disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer's disease (105 'probable' and 58 'possible', NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51. 5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer's disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer's disease.

Age Distribution