Alzheimer Disease: Poewe W

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.

Geser F, Wenning GK, Poewe W, McKeith I. · Clinical Department of Neurology, Medical University Innsbruck, Austria. · Mov Disord. · Pubmed #16092075 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people that has only been recognized in the past decade and that remains widely underdiagnosed. At postmortem examination, affected patients show numerous alpha-synuclein-positive Lewy bodies (LB) in many parts of the cerebral cortex, particularly neocortical and limbic areas in addition to the nigral LB degeneration characteristic of Parkinson's disease (PD). Clinical presentation, unlike PD, is with progressive cognitive decline with particular deficits of visuospatial ability as well as frontal executive function accompanied by usually only mildly to moderately severe parkinsonism, which is often akineto-rigid without the classical parkinsonian rest-tremor. Further accompanying features include spontaneous recurrent visual hallucinations and conspicuous fluctuations in alertness and cognitive performance. The two main differential diagnoses are Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). To improve the differential diagnosis of DLB, consensus criteria have been developed that establish possible and probable levels of clinical diagnostic accuracy. Generally, their sensitivity is variable and low but their specificity is high. Current consensus is to restrict a diagnosis of DLB only to patients with parkinsonism who develop dementia within 12 months of the onset of motor symptoms. Using operationalized criteria, DLB can be diagnosed clinically with an accuracy similar to that achieved for AD or PD. Ancillary investigations, particularly neuroimaging, can aid in differential diagnosis. We review the present state of the best practice in the clinical diagnosis of DLB. Future modifications of diagnostic criteria would ideally include the full range of clinical presentations that can be associated with LB disease.

Ransmayr G, Wenning GK, Seppi K, Jellinger K, Poewe W. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020 Innsbruck. · Nervenarzt. · Pubmed #11139988 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, parkinsonian syndrome, fluctuations of cognitive functions, alertness, and attention, visual hallucinations (usually detailed and well described), depression, REM sleep behavior disorder, adverse responses to standard neuroleptics doses, falls, syncopes, systematized delusions, and other modalities of hallucinations. Specificity of the clinical diagnostic criteria is high (95%), and sensitivity is considerably lower. Mean age at disease onset ranges between 60 and 68 years. The male gender prevails. Disease duration is 6 to 8 years. The differential diagnoses of DLB are dementia of the Alzheimer type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and rarely Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. Controlled pharmacological studies have so far not been published. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha receptor-blocking medications to improve neurogenic bladder dysfunction.

Barone P, Burn DJ, van Laar T, Hsu C, Poewe W, Lane RM. · Dipartimento di Scienze Neurologiche, Università Federico II di Napoli, Naples, Italy. · Mov Disord. · Pubmed #18581467 No free full text.

Abstract: The effects of rivastigmine versus placebo in Parkinson's disease dementia (PDD) patients with elevated or normal/low plasma homocysteine were determined. In this prospective analysis of a 24-week, randomly assigned, placebo-controlled study of rivastigmine in PDD, subpopulations comprised patients with plasma homocysteine >or=14 micromol/L (elevated) or <14 micromol/L (normal/low). Coprimary outcomes were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer Disease Cooperative Society-Clinical Global Impression of Change (ADCS-CGIC). Secondary outcomes included additional measures of cognition, including attention and executive function, daily function, and neuropsychiatric symptoms. Adverse events (AEs) were monitored. In total, 342 of 541 patients provided samples for analysis, from which 72% had elevated plasma homocysteine. Hyperhomocysteinemic patients showed treatment differences (rivastigmine vs. placebo) of 4.0 on ADAS-cog and 0.7 on ADCS-CGIC (both P < 0.01), and significant treatment differences on secondary outcomes. Rivastigmine- and placebo-treated hyperhomocysteinemic patients (16.5% and 14.6%) discontinued the study because of AEs. Patients with normal/low homocysteine showed no treatment differences on primary or secondary outcomes (1.4 on the ADAS-cog and 0.1 on ADCS-CGIC, both P = ns); 16.7% and 10.3% rivastigmine- and placebo-treated patients discontinued because of AEs. Elevated homocysteine was associated with greater rivastigmine treatment differences than normal/low homocysteine.

Ransmayr GN, Holliger S, Schletterer K, Heidler H, Deibl M, Poewe W, Madersbacher H, Kiss G. · Department of Neurology, Innsbruck Medical University, Austria. · Neurology. · Pubmed #18209204 No free full text.

Abstract: OBJECTIVE: The present study sought to investigate lower urinary tract symptoms and urodynamic and cystometric findings in Parkinson disease (PD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). METHODS: Included were patients with frequency, urgency, incontinence, and nocturia, without major bladder outflow obstruction. The protocol comprised physical examination, urine analysis, prostate specific antigen, 24-hours frequency of micturition, mean voided volume (MVV), free flow before instrumentation (Qmax(before)), post-void residual volume (PVR), and cystometry. RESULTS: Fifteen patients with DLB and PD and 16 patients with AD were examined. MVV, PVR, Qmax(before) and with transurethral catheter, cystometric bladder capacity, and detrusor pressor at maximum flow were similar in the three groups and corresponded to values of the general elderly population. Urge episodes and urge incontinence were observed in 93 and 53% of the patients with DLB, 53 and 27% of the patients with PD, and 19 and 12% of the patients with AD, and detrusor overactivity in 92% of the patients with DLB, 46% of the patients with PD, and 40% of the patients with AD. CONCLUSIONS: Urgency and urge incontinence suggest detrusor overactivity, which was more prevalent in dementia with Lewy bodies than in Parkinson disease and Alzheimer disease, whereas mean voided volume, free flow, cystometric bladder capacity, and detrusor pressor were similar in the groups. Frequency of micturition could not be reliably assessed in patients with dementia.

Poewe W. · Department of Neurology, Medical University of Innsbruck, Austria. · Mov Disord. · Pubmed #16092095 No free full text.

Abstract: Cognitive decline and dementia affect approximately 30% to 40% of patients with idiopathic Parkinson's disease during the course of their illness. PD-dementia (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in causing degenerative dementia in the elderly. The nosological distinction of the conditions has remained controversial because of broad clinical and pathological overlap. Treatment issues in both clinical settings are virtually identical. Treatment of Parkinsonism is often complicated by drug-induced psychosis and reduced levodopa responsiveness. Cognition, alertness, attention, as well as apathy or aggressive behavior have been shown to respond to treatment with cholinesterase inhibitors in randomized controlled trials both in DLB and PDD. Such treatment may also improve hallucinosis, but many patients will require add-on treatment with atypical neuroleptics to control drug-induced psychotic reactions. Clozapine and quetiapine are the drugs most commonly used and, contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause severe side effects according to published data.

Brenneis C, Wenning GK, Egger KE, Schocke M, Trieb T, Seppi K, Marksteiner J, Ransmayr G, Benke T, Poewe W. · Department of Neurology, University Hospital of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria. · Neuroreport. · Pubmed #15257132 No free full text.

Abstract: We determined brain atrophy patterns in dementia with Lewy bodies and Alzheimer's disease using voxel-based morphometry, an indirect volumetry. Ten patients with dementia with Lewy bodies, 10 patients with Alzheimer's disease and 10 controls were included. All groups were matched for age; sex and global differences in voxel intensities were included as confounding covariates. We observed basal forebrain atrophy discriminating dementia with Lewy bodies from Alzheimer's disease. Compared to controls, atrophy of lateral prefrontal cortex and left premotor cortex was seen in dementia with Lewy bodies whereas atrophy of the medial temporal cortex, posterior parietal cortex, thalamus and temporo-occipital areas was observed in Alzheimer's disease. Atrophy of insular cortex was found in both patient groups.

Jellinger KA, Seppi K, Wenning GK, Poewe W. · L. Boltzmann Institute of Clinical Neurobiology, Vienna, Austria. · J Neural Transm. · Pubmed #11956955 No free full text.

Abstract: OBJECTIVE: To assess the impact of coexisting Alzheimer (AD) pathology on the natural history of Parkinson's disease (PD). BACKGROUND: AD changes are frequently present in brains of demented PD patients. Assessing the relative contribution of AD pathology to the natural history of PD is difficult and the impact of both AD and cortical Lewy body (LB) pathologies on cognitive dysfunction is still under discussion. From clinical experience, dementia in PD patients, mainly related to AD pathology, is associated with a poor outcome, but the impact of AD pathology on the natural history of PD has not been studied systematically. MATERIAL AND METHODS: In 200 consecutive autopsy cases of PD (sex (m/f) ratio 1:1.1), age at death 58-98 (mean 77.0 +/- 9.5) years, from a specialized Austrian brain bank, retrospectively assessed major initial clinical symptoms (tremor, akinesia), moderate/severe dementia, and duration of illness were correlated with associated AD pathologies using CERAD, Braak and NIA-Reagan criteria. Mann-Whitney U-test, Cox-regression were used for statistical analysis. RESULTS: While gender had no influence on the clinical motor symptoms and outcome, tremor dominant type had a significantly better outcome than akinetic forms (p = 0.022), even after adjustment with age at onset and associated AD pathology (CERAD and Braak criteria). Patients with late onset showed significantly shorter duration of illness irrespective of dementia. Moderate to severe dementia, reported in 33% of the sample, was significantly correlated with AD pathology (all 3 criteria) that showed significantly negative correlation with survival: between CERAD 0-A vs. B and C there was a significant difference of odd ratios (p < 0.001), as was between Braak stages 0-2, 3-4.5, and 5, but not between Braak stages 3-4 and 5. CONCLUSIONS: The present data confirm previous studies suggesting better outcome of tremor-dominant than akinetic-rigid type of PD, significantly worse outcome in PD with late onset and dementia that is significantly correlated with coexistent neuritic Alzheimer pathology, particularly when using the CERAD and NIA-R criteria for the diagnosis of AD. Further studies are needed to elucidate the relative impact of cortical LB and AD pathologies on the natural history of PD.

Hanin I, Windisch M, Poewe W, Fisher A. · No affiliation provided · Neurodegener Dis. · Pubmed #18322365 No free full text.

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