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Objective: To determine variation in diagnostic strategies for diagnosing dementia between Dutch hospitals., Design: Descriptive, retrospective research based on claim data of Dutch health insurers., Method: Information on the use of diagnostic ancillary services carried out from 2015 to 2018 was collected via national-level insurance claims for patients who received a (new) diagnose-coding for dementia in 2018. Hospitals were included in the analysis if they diagnosed >50 patients with dementia. We distinguished academic medical centres (AMC), non-academic training hospitals (TH) and general hospitals (GH)., Results: In 2018, 20.073 new cases of dementia were diagnosed in 71 hospitals. The percentages of patients undergoing MRI/CT-imaging ranged from 37 to 99% (median 76.7%), neuropsychological-assessment from 0-89% (median 31.8%), cerebrospinal fluid examination from 0-14% (median 2.4%), PET/SPECT-imaging from 0-16% (median 6.2%) and electroencephalography from 1-20% (median 5.8%). Practice variation was comparable in AMCs, THs and GHs and was evidently skewed for PET/SPECT-imaging, electroencephalography and cerebrospinal fluid examination. There were no distinct differences according to case-mix characteristics or hospital volume. The percentage of patients subjected to ancillary diagnostic investigations decreased sharply with increasing age., Conclusion: In the Netherlands, diagnostic ancillary methods used vary widely between hospitals both in frequency and modality. This variation may be driven by limited evidence of diagnostic accuracy and added value of different diagnostic tests, variations in doctor and patient preferences and differences in available diagnostic techniques per hospital. Further exploration of this heterogeneity may help to identify a strategy that combines the most benefit with the least burden.

Recognizing delirium superimposed on pre-existing cognitive impairment or dementia, 'delirium superimposed on dementia' (DSD), is challenging because signs of delirium might be interpreted as symptoms of pre-existing cognitive dysfunction.In this paper, we review the literature on the role of electrencephalography (EEG) in the differential diagnosis of delirium, dementia and DSD.Conventional EEG, applying twenty to thirty electrodes, taking thirty minutes registration, is not feasible in psychogeriatric patients. Recent studies suggest that it is possible to reliably detect delirium using only a limited number of EEG electrodes for a short period of time.With this, use of EEG in the detection of delirium in patients with cognitive impairment or clinically manifest dementia could be possible.

Several cohort studies have shown that vascular risk factors including hypertension, hypercholesterolaemia, diabetes mellitus, smoking, obesity and lack of physical exercise in midlife and to a lesser extent in late life, are associated with an increased risk of dementia. The results from randomised controlled clinical trials on treatment of these risk factors are not conclusive for the effect on cognitive decline and dementia. Studies investigating the effect of a multi-component intervention aimed at vascular risk factors to prevent or slow down cognitive decline and dementia will hopefully give the answer as to whether such an intervention is efficacious. This requires large clinical trials in an elderly population with long follow-up and several competing risks, making it difficult from an organisational and methodological point of view. Major challenges for future studies are to select the optimal population, set the optimal treatment targets and select clinically relevant outcome parameters.

Objectives: Description of methodological issues in a trial designed to evaluate if a multi-component intervention aimed at vascular risk factors can prevent dementia., Design, Setting and Participants: Multi-center, open, cluster-randomized controlled clinical trial (preDIVA) including 3535 non-demented subjects aged 70-78, executed in primary practice and coordinated from one academic hospital. General practices are randomized to standard care or intensive vascular care., Intervention: Vascular care consists of 4-monthly visits to a practice nurse who monitors all cardiovascular risk factors. Hypertension, hypercholesterolemia, overweight, lack of physical exercise and diabetes are strictly controlled according to a protocol and treated in a way, tailored to the characteristics of individual participants., Measurements: Primary outcomes are incident dementia and disability; secondary outcomes are mortality, vascular events (stroke, myocardial infarction, peripheral vascular disease), cognitive decline and depression., Results: Between May 2006 and February 2009, 3535 subjects from 115 general practices have been included. The clusters have an average size of 31 (SD 22, range 2-114). 1658 Patients from 52 practices were randomized to the standard care condition and 1877 patients in 63 practices to the vascular care condition., Discussion: When designing a cluster-randomized trial, clustering of patient data within GP practices leads to a loss of power. This should be adjusted for in the power calculation. Since intensive vascular care will probably lead to a reduction in cardiovascular mortality, the competing risks of mortality and dementia should be taken into account.

Apolipoprotein E (APOE) is consistently associated with dementia in the general population. Findings on the role of this gene in persons with Down's syndrome (DS) are inconclusive. We studied the effects of APOE on mortality and dementia in a longitudinal prospective study of a large population-based sample of persons with DS (n=425), demented and non-demented. There was evidence that APOE epsilon4 is correlated with the rate of decline in the social competence rating scale (SRZ) (p=0.04). In our population, we found overall a modest but not statistical significant effect on the prevalence of dementia (OR=1.57, 95%CI: 0.87-2.82). We did observed a significant long-term effect on the incidence of dementia (HR=4.66, 95%CI: 1.35-16.14), but for those with a follow-up less than 3 years the risk was not significantly increased: HR=0.83 (95%CI 0.35-1.94). When pooling our data in a meta-analysis, the APOE epsilon4 allele shows a 1.59-fold (95%CI: 1.19-2.12) increase in risk of dementia in persons with DS. We conclude that APOE is influencing the risk of dementia in persons with DS.

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.

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., (Copyright 2004 Guarantors of Brain)

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.

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.

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.

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.

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.

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.

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.

The clinical features and disease course of six patients from a family with autosomal dominant inheritance of presenile dementia and a hypokinetic syndrome are described. In the past, these patients have carried diagnoses of Pick's disease, Huntington's disease, Parkinson-dementia, and one patient was described as suffering from a 'peculiar type of presenile dementia' in a case report. In the two cases examined, the most distinctive neuropathological features were extensive globular deposits of periodic acid-Schiff plus diastase (PAS)-positive material, having tinctural properties of amyloid only to a limited degree, in the cerebellum and cerebral cortex. These globules stained positively with antibodies against prion protein. Southern blot of MspI-digested genomic DNA showed an abnormal band of approximately 950 bp in all three patients from which material was available. Direct sequencing of the abnormal allele revealed an insert consisting of eight extra 24-nucleotide repeats in the patients, which was absent in a healthy first degree relative who was considered well beyond the age of onset of symptoms in this family. The nucleotide sequence of the abnormal insert of 192 bp was different from that of a previously described insert of equal length. Adding to previous descriptions of mutations in the prion protein gene, this report emphasizes the clinical, neuropathological and genetic heterogeneity of inherited prion disease.

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.

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. [ABSTRACT FROM AUTHOR]