Alzheimer Disease: Olde Rikkert MG

Verbeek MM, Olde Rikkert MG. · No affiliation provided · Clin Chem. · Pubmed #18824570 No free full text.

This publication has no abstract.

de Jong D, Kremer BP, Olde Rikkert MG, Verbeek MM. · Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. · Clin Chem Lab Med. · Pubmed #17970699 No free full text.

Abstract: In this comprehensive review, we summarize the current state-of-the-art of neurochemical biomarkers for Alzheimer's disease. Predominantly, these biomarkers comprise cerebrospinal fluid biomarkers directly related to the pathophysiology of this disorder (such as amyloid beta protein, tau protein). We particularly pay attention to the innovations in this area that have been made in technological aspects during the past 5 years (e.g., multiplex analysis of biomarkers, proteomics), to the discovery of novel, potential biomarkers (e.g., amyloid beta oligomers, isoprostanes), and to the extension of this research towards identification of biomarkers in plasma.

Schölzel-Dorenbos CJ, van der Steen MJ, Engels LK, Olde Rikkert MG. · Memory Clinic Slingeland Hospital, Alzheimer Centre Nijmegen, University Medical Centre Nijmegen, the Netherlands. · Alzheimer Dis Assoc Disord. · Pubmed #17545745 No free full text.

Abstract: We conducted a systematic review of the use of quality of life (QoL) measures as outcome in pharmacological and nonpharmacologic intervention trials in patients with Mild Cognitive Impairment or dementia, and their proxies. Randomized controlled trials (RCTs) were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group in April 2006. We also checked references and systematic reviews. Primary and secondary end points were screened for QoL-scales, and it was registered whether information on responsiveness was provided. We found 117 pharmacologic and 108 nonpharmacologic RCTs. One of the pharmacologic and 4 of the nonpharmacologic studies used QoL as primary outcome, and 2 and 3, respectively, as secondary end point. Altogether QoL was assessed in only 10 (4.4%) of these RCTs, of which 2 reported on responsiveness of QoL. This review provides evidence that QoL-instruments are seldom used as outcome measures in RCTs in dementia and Mild Cognitive Impairment, and that information on responsiveness is scarce. QoL-measures should be applied more often in clinical trials, as currently no disease modifying drugs are available, although there are valid and reliable QoL-measures for dementia that reflect the aims of palliative care and provide transparent information about patient's and caregiver's treatment benefits. We recommend further research efforts aimed at the determination of the minimal important difference in QoL-scales and the responsiveness of QoL-scales. Subsequently, QoL should be measured as relevant end point, both in patients and their proxies, in all clinical trials in dementia.

de Leeuw FE, van Norden AG, van der Flier WM, Olde Rikkert MG, Scheltens P. · Universitair Medisch Centrum St Radboud, Huispostnummer 326, Postbus gIoI, 6500 HB Nijmegen. · Ned Tijdschr Geneeskd. · Pubmed #16398165 No free full text.

Abstract: There is increasing evidence that vascular risk factors including hypertension, high cholesterol, hyperhomocysteinaemia and diabetes mellitus are connected to the risk of Alzheimer's disease (AD). The risk of AD may be reduced by the treatment of hypertension prior to onset of cognitive impairment. One small randomised clinical trial has provided some evidence of beneficial effects on cognition of cholesterol-lowering drugs such as the statins in patients with AD. Treatment of hypertension, hyperhomocysteinaemia and diabetes mellitus with the aim of halting the progression of cognitive decline in AD is still under study and results are awaited. For the time being findings from the trials carried out thus far should be interpreted with care due to methodological shortcomings, both in study design and execution. In order to investigate the role of vascular risk factors both in the aetiology and treatment of AD, large prospective randomised trials with long-term follow-up of AD patients who have been diagnosed using revised uniform diagnostic criteria that take the heterogeneity of the disease into account, are necessary.

Olde Rikkert MG, Rigaud AS. · Dept. Geriatric Medicine, University Hospital Nijmegen, Code 318, PO Box 9101, 6500 HB Nijmegen, The Netherlands. · Z Gerontol Geriatr. · Pubmed #11828891 No free full text.

Abstract: BACKGROUND: Melatonin is a hormone and antioxidant produced by the pineal gland of which four neurobiological roles have been claimed in the aged population: anti-ageing agent; free-radical scavenger; regulator of circadian rhythm; endogeneous sleep-inducer. The "melatonin replacement" hypothesis states that 1) the well-evidenced age-related decline contributes to insomnia and that 2) replacement with physiological doses of melatonin improves sleep. The aim of this review was to determine the evidence for the efficacy of melatonin in elderly insomniacs. METHODS: MEDLINE's database from 1990-2000 was searched with "melatonin", "geriatrics" and "(frail)-elderly" as major sub-headings. This resulted in 78 articles: only studies with empirical treatment data were reviewed (N = 12). RESULTS: Six reports (abstract, research letter, retrospective case study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep quality improved and in patients with Alzheimer's disease sundowning was reduced. In 6 double blind, randomised crossover trials, a total number of 95 patients (mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6 mg; most took a single dose 30-120 min before bedtime. In 3 studies a slow release form was used. Sleep quality was objectively measured by wrist actigraphy (n = 4) and polysomnography (n = 2), and additionally subjective sleep quality was assessed (n = 2). Sleep latency decreased significantly in 4 studies. In 3 studies other measures of sleep quality (sleep efficiency, total sleep time and wake time during sleep) improved. Subjective sleep quality did not improve. No early-morning sleepiness occurred. Comparison of the studies suggests that melatonin is most effective in elderly insomniacs who chronically use benzodiazepines and/or with documented low melatonin levels during sleep. CONCLUSION: There is sufficient evidence that low doses of melatonin improve initial sleep quality in selected elderly insomniacs. However, larger randomized controlled trials, with less strict inclusion criteria are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric patients who suffer from insomnia, before wide-spread use can be advocated.

Schölzel-Dorenbos CJ, Draskovic I, Vernooij-Dassen MJ, Olde Rikkert MG. · Memory Clinic Slingeland Hospital/Alzheimer Centre Nijmegen, University Medical Centre Nijmegen, Kruisbergseweg 25, Doetinchem 7009 BL, The Netherlands. · Alzheimer Dis Assoc Disord. · Pubmed #19484919 No free full text.

Abstract: The objective of the study was to explore, in a sample of spouses of mild-to-moderate Alzheimer disease patients, predictors of quality of life (QoL) by rating QoL and burden. The authors assessed 97 spouses in a cross-sectional study with the Schedule for the Evaluation of Individual Quality of Life (SEIQoL), Self-Rated Burden scale (SRB), self-perceived stress scale (EDIZ; Ervaren Druk door Informele Zorg/Self-Perceived Pressure from Informal Care), and Zarit Burden Interview (ZBI). Patient cognition was rated with the Mini-Mental State Examination (MMSE). Factors best predicting QoL were analyzed with multiple regression analysis. Eighty-seven (53% male, mean 72 y) fulfilled the SEIQoL internal reliability criteria, and had a mean SEIQoL score of 68.6+/-14.8. Most important QoL domains were condition of patient (31%) and marriage (26%). Caregiver burden scores on SRB, Ervaren Druk door Informele, Zorg, and ZBI were 44.1+/-23.5 (n=67), 4.9+/-2.2 (n=53), and 13.1+/-6.2 (n=53), respectively. Mean patient MMSE score (0 to 30) was 20.3+/-4.2. Spouses experienced lower QoL than Alzheimer disease patients and healthy elderly (historical controls), and perceived moderate levels of burden. Patient cognition is a significant predictor of caregiver QoL. Burden, measured by ZBI, is significantly negatively correlated with SEIQoL. The results underline the importance of implementing health services known to improve QoL and alleviate burden, and to explore new effective interventions.

van der Vorm A, Vernooij-Dassen MJ, Kehoe PG, Olde Rikkert MG, van Leeuwen E, Dekkers WJ. · Radboud University Nijmegen Medical Centre, IQ Healthcare, Section of Ethics, Philosophy and History of Medicine, 114 IQ Healthcare, Nijmegen, The Netherlands. · J Med Ethics. · Pubmed #19181890 No free full text.

Abstract: BACKGROUND: Although genetic research into Alzheimer disease (AD) is increasing, the ethical aspects of this kind of research and the differences between ethical issues related to genetic and non-genetic research into AD have not yet received much attention. OBJECTIVES: (1) To identify and compare the five ethical issues considered most important by surveyed expert panellists in non-genetic and genetic AD research and (2) to compare our empirical findings with ethical issues in genetic research in general as described in the literature. Method: A modified Delphi study in two rounds RESULTS: Genetic and non-genetic research into AD generated an approximately equal number of topics with a considerable overlap. Different priorities in the ethics of both types of research were found. Genetic research raised new topics such as "confidentiality of genetic information" and "implications of research for relatives" which changes the impact and application of existing ethical topics such as "informed consent" and is judged to have more impact on both individuals and society. A difference with the results of more theoretical approaches on ethical aspects related to AD research was also found. CONCLUSIONS: Different priorities are given to ethical issues in genetic and non-genetic research. These arise partly because genetic research causes unique and new questions, mostly related to the position of family members and the status of and access to genetic information. Differences found between the results of our empirical study and the more theoretical literature, suggest an additional value for empirical research in medical ethics.

Olde Rikkert MG, van der Vorm A, Burns A, Dekkers W, Robert P, Sartorius N, Selmes J, Stoppe G, Vernooij-Dassen M, Waldemar G. · Department of Geriatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. · Am J Alzheimers Dis Other Demen. · Pubmed #18509105 No free full text.

Abstract: In this article, the authors describe how the European Dementia Consensus Network developed a consensus on research ethics in dementia, taking into account the questions posed by the era of genetic research and its new research methods. The consensus process started with a Delphi procedure to analyze relevant stakeholders' positions by describing their statements on the possibilities and limitations of research into genetic determinants of Alzheimer disease and to describe and analyze the moral desirability of genetic research on Alzheimer disease. The conclusions drawn from the Delphi procedure fuelled the development of the consensus statement, which is presented in this paper. The consensus statement aims to stimulate ethically acceptable research in the field of dementia and the protection of vulnerable elderly patients with dementia from application of inadequate research methods or designs.

van Iersel MB, Hoefsloot W, Munneke M, Bloem BR, Olde Rikkert MG. · Department of Geriatrics and Neurology, University Medical Center St. Radboud, Njimegen, The Netherlands. · Z Gerontol Geriatr. · Pubmed #14991293 No free full text.

Abstract: INTRODUCTION: Diminished mobility often accompanies dementia and has a great impact on independence and quality of life. New treatment strategies for dementia are emerging, but the effects on gait remains to be studied objectively. In this review we address the general effects of dementia on gait as revealed by quantitative gait analysis. METHODS: A systematic literature search with the (MESH) terms: 'dementia' and 'gait disorders' in Medline, CC, Psychlit and CinaHL between 1980-2002. Main inclusion criteria: controlled studies; patients with dementia; quantitative gait data. RESULTS: Seven publications met the inclusion criteria. All compared gait in Alzheimer's Disease (AD) with healthy elderly controls; one also assessed gait in Vascular Dementia (VaD). The methodology used was inconsistent and often had many shortcomings. However, there were several consistent findings: walking velocity decreased in dementia compared to healthy controls and decreased further with progressing severity of dementia. VaD was associated with a significant decrease in walking velocity compared to AD subjects. Dementia was associated with a shortened step length, an increased double support time and step to step variability. DISCUSSION: Gait in dementia is hardly analyzed in a well-designed manner. Despite this, the literature suggests that quantitative gait analysis can be sufficiently reliable and responsive to measure decline in walking velocity between subjects with and without dementia. More research is required to assess, both on an individual and a group level, how the minimal clinically relevant changes in gait in elderly demented patients should be defined and what would be the most responsive method to measure these changes.