Alzheimer Disease: Schmidt R

Ransmayr G, Katzenschlager R, Dal-Bianco P, Wenning G, Bancher C, Jellinger K, Schmidt R, Poewe W. · Neurologische Universitätsklinik Graz, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #17640492 No free full text.

Abstract: Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis. We also guide in the management of DLB as pharmacological treatment can pose difficult dilemmas for the treating clinician.

Klie T, Schmidt R. · No affiliation provided · Z Gerontol Geriatr. · Pubmed #12219701 No free full text.

This publication has no abstract.

Förstl H, Werheid K, Ulm K, Schönknecht P, Schmidt R, Pantel J, Hörr R, Gutzmann H, Gertz HJ, Frölich L, Bickel H. · Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München. · Dtsch Med Wochenschr. · Pubmed #19142839 No free full text.

Abstract: Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer's disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes.

Schmidt R, Neff F, Lampl C, Benke T, Anditsch M, Bancher C, Dal-Bianco P, Reisecker F, Marksteiner J, Rainer M, Kapeller P, Dodel R. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18826870 No free full text.

Abstract: Cholinesterase inhibitors and memantine can slow the course of Alzheimer's disease. In Austria the frequency of treatment is in the upper third among countries of the EU. Yet, the majority of Alzheimer patients does not receive adequate medication. Compliance to treatment is low. Studies on cholinesterase inhibitors show that only one third and one fifth of patients adhere to medication after 3 months and 12 months, respectively. Causes for low compliance are only partly patient-related, many factors are system-inherent. Knowledge of these factors is a pre-requisite for the treating physician to improve current unfavourable situation. Present treatment strategies are symptomatic, causal disease-modifying therapies are urgently needed. Research activity in the field is high and dominated by the amyloid hypothesis. We here review the basis and recent studies on secretase-inhibitors, immunization, aggregation of Abeta, statins and PPARgamma-agonists. Research towards strategies against tau-pathology is less dominant and focuses on inhibition of kinases and increase of activity of phosphatases. Causal therapies would have great effects on a population basis even if efficacy is only moderate. A disease-modifying therapy which delays the onset of Alzheimer disease by 5 years, will probably reduce the number of patients by nearly 50% during the next 50 years.

Schmidt R, Kienbacher E, Benke T, Dal-Bianco P, Delazer M, Ladurner G, Jellinger K, Marksteiner J, Ransmayr G, Schmidt H, Stögmann E, Friedrich J, Wehringer C. · Univ.-Klinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18381051 No free full text.

Abstract: The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.

Fazekas F, Enzinger C, Ropele S, Schmidt H, Schmidt R, Strasser-Fuchs S. · Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · J Neurol Sci. · Pubmed #16631796 No free full text.

Abstract: Epidemiological studies provide strong evidence that susceptibility to multiple sclerosis (MS) is in part genetically determined. Likewise the heterogeneity in clinical manifestations, temporal course, severity, and in the pathological processes of MS are probably also influenced by our genes. Apolipoprotein E (apoE) polymorphism has been considered a candidate for impacting on MS because of its numerous functions related to brain tissue and evidence for an association with a variety of cerebral disorders, specifically Alzheimer's disease (AD). The apoE alleles epsilon2, epsilon3, and epsilon4 are known to impact differently on aspects such as neuronal growth and repair, neuroprotection and inflammation. After a review of the strong association of the apoE polymorphism with AD, we review the results on MS. These are far less homogenous but have gained support from morphologic and metabolic measures obtained with magnetic resonance imaging indicating a greater extent of brain destruction with the apoE epsilon4 allele. Evidence for a protective role of the epsilon2 allele in MS is weak. In view of the association with AD it is tempting to speculate that neuropsychologic functioning in MS might be even more strongly related to the apoE polymorphism and especially to the epsilon4 allele than other deficits, but few data on this issue are yet available. While part of the association of the apoE polymorphism with AD is supposed to be caused by apoE-isoform dependent effects on amyloid-beta deposition, no single pathogenetically relevant mechanism has yet been confirmed for MS. In summary we presently may assume only subtle effects of the apoE polymorphism on the course of MS. These effects are probably further modulated by other genes and need further investigation.

Schmidt R, Schmidt H, Fazekas F. · Department of Neurology, Karl-Franzens University Graz, Austria. · J Neurol. · Pubmed #10751108 No free full text.

Abstract: This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer's disease. There is also evidence of a direct relationship between Alzheimer's disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer's disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.

Leys D, Erkinjuntti T, Desmond DW, Schmidt R, Englund E, Pasquier F, Parnetti L, Ghika J, Kalaria RN, Chabriat H, Scheltens P, Bogousslavsky J. · University of Lille, France. · Alzheimer Dis Assoc Disord. · Pubmed #10609680 No free full text.

Abstract: Although vascular dementia (VaD) is the second most frequent cause of dementia after Alzheimer disease (AD), the concept remains controversial in terms of delineation. The objective of this review is to investigate, from available literature, the role of cerebral infarcts in the pathogenesis of VaD and to identify areas of interest that need further evaluation and research. The incidence of new onset dementia is increased after stroke. Stroke subtypes, total volume of cerebral infarction and functional tissue loss, and location of the lesions are probably the major determinants of VaD. Any cause of stroke can lead to VaD. In some circumstances the causal relation between stroke and dementia is clear: (1) in young patients who are unlikely to have associated Alzheimer pathology; (2) when the cognitive functioning was normal before stroke, impaired immediately after, and does not worsen over time; (3) when the lesions are located in strategic areas; and (4) when a well-defined vasculopathy known to cause dementia is proven. However, several issues remain unsolved in VaD: lack of specificity of the diagnostic criteria; influence of white matter changes and associated Alzheimer pathology; influence of preexisting cognitive status; possibility of having VaD without stroke and the clinical relevance of silent infarcts to VaD; and best therapeutic strategy to be used to prevent VaD and to prevent stroke in patients with VaD. These questions form the basis for proposals for future research.

Schmidt R, Alf C, Bancher C, Benke T, Berek K, Dal-Bianco P, Führwürth G, Imarhiagbe D, Jagsch C, Lechner A, Rainer M, Reisecker F, Rotaru J, Uranüs M, Walter A, Winkler A, Wuschitz A. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #19272293 No free full text.

Abstract: We performed a 6-month open-label study on the use of the transdermal rivastigmine patch in clinical routine in 103 patients with Alzheimer's disease from 25 outpatient services in Austria. After baseline, safety and tolerability of the 10 cm2--rivastigmine patch was assessed at week 4, 12 and 24 in all patients. A Mini Mental State Examination was done at baseline and at week 12 and 24. Skin adherence of the patch was very good or good in 85% of study participants. Only 2.9% of patients had gastrointestinal adverse events. Local skin reactions occurred in 23% of individuals. Skin alteration were mostly mild in severity. In only 6.8% of subjects did they result in termination of treatment. At the earliest skin reactions were observed after 3 months of treatment. Cognitive functioning of patients improved comparable to the controlled trial which led to approval of the rivastigmine patch. In daily routine the safety profile of the rivastigmine patch is favourable, as is the response to treatment. Local, mostly mild skin reactions affect approximately every fifth patient, and they occur relatively late in the course of therapy. Patients and their caregivers should receive detailed information about skin reactions to omit unnecessary drop outs to treatment.

Schmidt R, Lechner A, Petrovic K. · Department of Neurology, Karl Franzens University Graz, Austria. · Int Clin Psychopharmacol. · Pubmed #11890189 No free full text.

Abstract: We performed an open-label study in Alzheimer patients on the use of rivastigmine in clinical routine. We evaluated the mode of dosing, safety and response to treatment over 24 weeks in 529 Alzheimer patients recruited by 114 neurologists. At the start of the study, and after 12 and 24 weeks, the participants were tested with the Mini-Mental State Examination and the Global Deterioration Scale. Titration of rivastigmine was slower than expected: After 2 weeks, only 41.8% of subjects received an effective daily dose of at least 6 mg. A total of 33.8% of patients experienced 305 mostly transient adverse events of mild or moderate intensity. Gastrointestinal symptoms occurred in 30.4% of subjects and symptoms of the nervous system in 16.4%. Similar to controlled trials, the cognitive performance of patients improved, with more than 60% of subjects showing improvement from baseline on the Mini-Mental State Examination by week 24. More than 40% of patients showed improvement on the Global Deterioration Scale. This study suggests that, in daily clinical practice, titration of rivastigmine deviates from the prescribing information. Under routine conditions, the safety profile of the drug is favourable, as is the response to treatment.

Ruether E, Husmann R, Kinzler E, Diabl E, Klingler D, Spatt J, Ritter R, Schmidt R, Taneri Z, Winterer W, Koper D, Kasper S, Rainer M, Moessler H. · Goettingen University Clinic for Psychiatry, Germany. · Int Clin Psychopharmacol. · Pubmed #11552768 No free full text.

Abstract: Cerebrolysin (Cere) is a compound with neurotrophic activity which has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. The efficacy and safety of repeated treatments with Cere were investigated in this randomized, double-blind, placebo-controlled, parallel-group study. One hundred and forty-nine patients were enrolled (76 Cere; 73 placebo). Patients received i.v. infusions of 30 ml Cere or placebo 5 days per week for 4 weeks. This treatment was repeated after a 2-month therapy-free interval. Effects on cognition and clinical global impressions were evaluated 4, 12, 16, and 28 weeks after the beginning of the infusions using the Clinical Global Impression (CGI) and the Alzheimer's Disease Assessment Scale-cognitive subpart (ADAS-cog). All assessments, including the 28-week follow-up visit were performed under double-blind conditions. At week 16, the responder rate of the Cere group was 63.5% on the CGI, compared to 41.4% in the placebo group (P < 0.004). In the ADAS-cog, an efficacy difference of 3.2 points in favour of Cere was observed (P < 0.0001). Notably, improvements were largely maintained in the Cere group until week 28, 3 months after the end of treatment. Adverse events were recorded in 43% of Cere and 38% of placebo patients. Cere treatment was well tolerated and led to significant improvement in cognition and global clinical impression. A sustained benefit was still evident 3 months after drug withdrawal.

Schmidt R, Ropele S, Pendl B, Ofner P, Enzinger C, Schmidt H, Berghold A, Windisch M, Kolassa H, Fazekas F. · Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · J Neurol Neurosurg Psychiatry. · Pubmed #18586865 links to  free full text

Abstract: OBJECTIVE: To study the feasibility of multimodal neuroimaging in mild to moderate Alzheimer disease (AD) and to estimate the size of possible treatment effects of memantine on potential functional, structural and metabolic biomarkers of disease progression. METHODS: In this randomised, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20 mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations. RESULTS: In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total brain volume by 2.1% (p<0.001) and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs 4.0%). No between-group differences were seen for changes in total brain volume. CONCLUSIONS: The results support the use of multimodal imaging including MRI and positron emission tomography (PET) to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. The data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.

Gouw AA, van der Flier WM, Fazekas F, van Straaten EC, Pantoni L, Poggesi A, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G, Schmidt R, Scheltens P, Barkhof F, Anonymous00402. · Department of Neurology, Alzheimer Center and Image Analysis Center, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. · Stroke. · Pubmed #18323505 links to  free full text

Abstract: BACKGROUND AND PURPOSE: We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development. METHODS: Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes. RESULTS: WMH progressed (mean+/-SD=1.9+/-1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes. CONCLUSIONS: WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.

Gouw AA, van der Flier WM, van Straaten EC, Pantoni L, Bastos-Leite AJ, Inzitari D, Erkinjuntti T, Wahlund LO, Ryberg C, Schmidt R, Fazekas F, Scheltens P, Barkhof F, Anonymous00397. · Alzheimer Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Cerebrovasc Dis. · Pubmed #18216467 No free full text.

Abstract: BACKGROUND: Investigating associations between the change of white matter hyperintensities (WMH) and clinical symptoms over time is crucial for establishing a causal relationship. However, the most suitable method for measuring WMH progression has not been established yet. We compared the reliability and sensitivity of cross-sectional and longitudinal visual scales with volumetry for measuring WMH progression. METHODS: Twenty MRI scan pairs (interval 2 years) were included from the Amsterdam center of the LADIS study. Semi-automated volumetry of WMH was performed twice by one rater. Three cross-sectional scales (Fazekas Scale, Age-Related White Matter Changes Scale, Scheltens Scale) and two progression scales (Rotterdam Progression Scale, Schmidt Progression Scale) were scored by 4 and repeated by 2 raters. RESULTS: Mean WMH volume (24.6 +/- 27.9 ml at baseline) increased by 4.6 +/- 5.1 ml [median volume change (range) = 2.7 (-0.6 to 15.7) ml]. Measuring volumetric change in WMH was reliable (intraobserver:intraclass coefficient = 0.88). All visual scales showed significant change of WMH over time, although the sensitivity was highest for both of the progression scales. Proportional volumetric change of WMH correlated best with the Rotterdam Progression Scale (Spearman's r = 0.80, p < 0.001) and the Schmidt Progression Scale (Spearman's r = 0.64, p < 0.01). Although all scales were reliable for assessment of WMH cross-sectionally, WMH progression assessment using visual scales was less reliable, except for the Rotterdam Progression scale which had moderate to good reliability [weighted Cohen's kappa = 0.63 (intraobserver), 0.59 (interobserver)]. CONCLUSION: To determine change in WMH, dedicated progression scales are more sensitive and/or reliable and correlate better with volumetric volume change than cross-sectional scales.

Ylikoski R, Jokinen H, Andersen P, Salonen O, Madureira S, Ferro J, Barkhof F, van der Flier W, Schmidt R, Fazekas F, Scheltens P, Waldemar G, Salvadori E, Pantoni L, Inzitari D, Erkinjuntti T, Anonymous00192. · Memory Research Unit, Department of Neurology, University of Helsinki, Helsinki, Finland. · Dement Geriatr Cogn Disord. · Pubmed #17565216 No free full text.

Abstract: BACKGROUND/AIMS: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs). METHODS: In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change. RESULTS: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog. CONCLUSIONS: The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain.

Korf ES, van Straaten EC, de Leeuw FE, van der Flier WM, Barkhof F, Pantoni L, Basile AM, Inzitari D, Erkinjuntti T, Wahlund LO, Rostrup E, Schmidt R, Fazekas F, Scheltens P, Anonymous00104. · Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. · Diabet Med. · Pubmed #17257279 No free full text.

Abstract: HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.

van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P. · Alzheimer Center, Department of Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Stroke. · Pubmed #16141425 links to  free full text

Abstract: BACKGROUND AND PURPOSE: On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. METHODS: Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). RESULTS: In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. CONCLUSIONS: We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.

Marksteiner J, Schmidt R. · Department of Psychiatry, Medical University Innsbruck, Innsbruck, Austria. · Drugs Aging. · Pubmed #15132710 No free full text.

Abstract: Complex interactive effects of genetic predisposition, neurochemical changes and disease comorbidity have been elucidated in the genesis of dementia syndromes. Alzheimer's disease is the most prevalent type of dementia in developed Western countries. In Alzheimer's disease, pharmacological treatment aims at symptomatic relief, disease modification or disease prevention. Cholinesterase inhibitors are established for the treatment of mild-to-moderate Alzheimer's disease. In Europe and the US, memantine is approved for the treatment of moderate-to-severe Alzheimer's disease. To date, there are no drugs with a disease modifying action that have proven efficacy in randomised, double-blind, placebo-controlled clinical trials. In patients not fulfilling the diagnostic criteria for early Alzheimer's disease, e.g. mild cognitive impairment, the efficacy of several drugs, mainly cholinesterase inhibitors, is currently tested in prospective studies by determining the conversion rate to Alzheimer's disease. However, prevention and disease-modifying strategies raise ethical questions because interventions are focused on non-diseased elderly at risk, which means that emphasis should be not only on efficacy but also on long-term safety. No disease-modifying strategy can presently be offered to patients; however, given the pace of recent research there is optimism that slowing progression of Alzheimer's disease will soon be possible.

van Straaten EC, Scheltens P, Knol DL, van Buchem MA, van Dijk EJ, Hofman PA, Karas G, Kjartansson O, de Leeuw FE, Prins ND, Schmidt R, Visser MC, Weinstein HC, Barkhof F. · Department of Neurology and Alzheimer Center, VU Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, Netherlands. · Stroke. · Pubmed #12855825 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

Klie T, Schmidt R. · Evangelische Fachhochschule Freiburg Bugginger Strasse 38 79114 Freiburg. · Z Gerontol Geriatr. · Pubmed #12219705 No free full text.

Abstract: The demographic and epidemiological scenarios, concerning persons with dementia, are in tension between the legal general conditions of care, on the one hand, and the conceptual alignment, on the other hand; this tension is hardly resolved by the momentary activities in health and care policy. Even on the level of assessment, there are scarcely any instruments to picture the specific needs of patients with dementia. Concepts of supply for persons with dementia are widely still divided by the differentiation between stationary and outpatient. Intelligent mixtures and paradigmatic reorientation towards normalization or split responsibility have not yet enfolded their embossing effects in practice. The care of persons with dementia is in many respects still bound in pre-technical constellations: this applies to the conceptual bias inside an institution or service of old people's care, to legal and economical general conditions and instruments of control and in many ways also to the technical discourse. The relevancy of attendance of people with dementia today and in the future justifies talking about "dementia policy". Options for dementia policy lay in a consequent adaptation of the theory of the New Welfare Mix, which was developed by the political sciences, including discussion about normalization in the area of help for disabled people and in the reformulation of competence between the means of fringe benefits and employees' benefits in joint responsibility.

Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. · Department of Neurology, Karl-Franzens University, Graz, Austria. · Ann Neurol. · Pubmed #12210786 No free full text.

Abstract: Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long-term prospective association between dementia and high-sensitivity C-reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968-1970) and subsequently were reexamined 25 years later for dementia in the Honolulu-Asia Aging Study (1991-1996). In a random subsample of 1,050 Honolulu-Asia Aging Study cases and noncases, high-sensitivity C-reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high-sensitivity C-reactive protein, men in the upper three quartiles had a 3-fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.

Schmidt R. · Neurologische Universitätsklinik, Auenbruggerplatz 22, A-8036 Graz. · Wien Med Wochenschr. · Pubmed #11925778 No free full text.

Abstract: The past decade has seen a renewed interest in vascular dementia. The search for a causal relationship between a vascular event or a vascular cerebral lesion and dementia has led to new classification schemes which no longer consider vascular dementia a homogeneous entity but acknowledge the diversity of the clinical and morphological substrates of this syndrome. Deviation from the term "multi-infarct dementia" is only one but many consequencies of these recent developments. Etiologically, vascular dementia may result from cerebral small vessel disease leading to extensive leucencephalopathy or lacunes or may be the consequence of strategically located infarcts or multiple infarcts in large vessel territories. It may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage or other mechanisms such as vasculitis. There is no definitive medical or surgical treatment for vascular dementia. Thus, it appears that stroke prevention offers the most immediate and substantial solution to reduce the morbidity and mortality. This is best substantiated for treatment of arterial hypertension. Once vascular dementia occurs control of vascular risk factors may be useful but this contention will require larger scale studies to provide more definite proof. A number of metabolically active drugs has been used for the treatment of cognitive symptoms in vascular dementia. Yet, the data are conflicting und the effects described modest at most. There is epidemiological evidence for a more than incidental co-existence between vascular and primary degenerative dementia which suggests that therapies found to be effective in Alzheimer's disease may also prove beneficial at least in subgroups of vascular dementia. Lately, this concept is tested by several studies on the efficacy of acetylcholinesterase inhibitors in vascular dementia.