Using static and dynamic canonical correlation coefficients as quantitative EEG markers for Alzheimer's disease severity.

We analyzed the relation between Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores and quantitative electroencephalographic (qEEG) markers that were derived from canonical correlation analysis. This allowed an investigation of EEG synchrony between groups of EEG channels. In this study, we applied the data from 79 participants in the multi-centric cohort study PRODEM-Austria with probable AD. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. A quadratic regression model was used to describe the relation between MMSE and the qEEG synchrony markers. This relation was most significant in the δ and θ frequency bands in resting state, and between left-hemispheric central, temporal and parietal channel groups during the cognitive task. Here, the MMSE explained up to 40% of the qEEG marker's variation. QEEG markers showed an ambiguous trend, i.e. an increase of EEG synchrony in the initial stage of AD (MMSE>20) and a decrease in later stages. This effect could be caused by compensatory brain mechanisms. We conclude that the proposed qEEG markers are closely related to AD severity. Despite the ambiguous trend and the resulting diagnostic ambiguity, the qEEG markers could provide aid in the diagnostics of early-stage AD.

Acute-onset migrainous aura mimicking acute stroke: MR perfusion imaging features.

BACKGROUND AND PURPOSE: In a very limited number of cases, acute migrainous aura may mimic acute brain infarction. The aim of this study was to recognize patterns of MR perfusion abnormalities in this presentation. MATERIALS AND METHODS: One thousand eight hundred fifty MR imaging studies performed for the suspicion of acute brain infarction were analyzed retrospectively to detect patients with acute migrainous aura not from stroke. All patients were examined clinically by 2 neurologists and underwent a standard stroke MR imaging protocol, including PWI. Two radiologists reviewed the perfusion maps visually and quantitatively for the presence, distribution, and grade of perfusion abnormalities. RESULTS: Among 1850 MR imaging studies, 20 (1.08%) patients were found to have acute migrainous aura. Hypoperfusion was found in 14/20 patients (70%) with delayed rMTT and TTP, decreased rCBF, and minimal decrease in rCBV. In contrast to the typical pattern in stroke, perfusion abnormalities were not limited to a single vascular territory but extended to >1. Bilateral hypoperfusion was seen in 3/14 cases. In 11/14 cases, hypoperfusion with a posterior predominance was found. TTP and rMTT were the best maps to depict perfusion changes at visual assessment, but also rCBF maps demonstrated significant hypoperfusion in quantitative analysis. In all patients, clinical and imaging follow-up findings were negative for stroke. CONCLUSIONS: Acute migrainous aura is rare but important in the differential diagnosis among patients with the suspicion of acute brain infarction. Atypical stroke perfusion abnormalities can be seen in these patients.

Physical, occupational, speech and swallowing therapies and physical exercise in Parkinson's disease.

Former studies on the effects of physical exercise, physical and occupational therapy (PT, OT) and speech and swallowing therapy (ST, SwT) in Parkinson's disease (PD) have demonstrated little or uncertain effects. New pathophysiological concepts have been developed. Recent controlled high-level studies demonstrate improvement of mobility and balance after training of muscular strength and endurance, trunk control, and amplitude and rhythmicity of movements (treadmill). Attentional and cognitive strategies were found to enforce body awareness and improve movement sequences. Dance, sensory (auditory, visual, tactile) and cognitive cueing are effective for problems of gait and balance. Whether PT and OT reduce the risk of falls remains uncertain. ST including Lee Silverman Voice Treatment has been shown to relieve speech problems. SwT and OT are frequently applied, however, further studies are necessary. Therapeutic interventions need to be evaluated with regard to consistency, intensity, frequency, duration, side effects, home versus institution based and standardized versus individualized training, quality standards, practicability in real life, and cost-effectiveness. Parkinson patients should resume or continue physical exercise as long as possible. There is hope that regular sport may modify PD risk and progression.

Reliability of the noninvasive sequence methods to estimate baroreflex function using the paradigm of brain death.

BACKGROUND: Various techniques have been developed to estimate spontaneous baroreflex sensitivity noninvasively. However, in the EuroBaVar study it has been shown that they yield differing results. AIM OF THE STUDY: To investigate the reliability of these methods further we compared the results of the most common sequence techniques. We used the paradigm of brain death with the absence of any baroreflex function. METHODS: In a prospective study we recorded breathing pattern, ECG and continuous blood pressure in 10 consecutive brain dead subjects of a neurointensive care unit. EuroBaVar sequence techniques 12-18 (ST12-ST18) were applied to the data sets and the number of sequences compared. RESULTS: Techniques which are based on thresholds in terms of blood pressure or R-R interval changes yielded the least false positive results: technique ST12, ST13, and ST14 detected very few sequences, while ST18 detected no sequence at all. Techniques using a correlation threshold (ST15-ST17) found a high number. CONCLUSION: This study demonstrates clearly that many of the sequence techniques used to estimate baroreflex sensitivity render false positive results in the unique paradigm of brain death. Thus, the method should be selected with regard to the biological signal and the pathophysiological background.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Lower urinary tract symptoms in dementia with Lewy bodies, Parkinson disease, and Alzheimer disease.

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.

[Clinical criteria of Parkinson's disease]. / Klinik des Morbus Parkinson.

The clinical criteria of Parkinson's disease are akinesia in combination with at least one of the following three symptoms: tremor (asymmetrical resting tremor), rigidity, impairment of posture, gait and balance. Symptomatic and atypical parkinsonian syndromes are ruled out by history, clinical examination, cranial CT, MRI, SPECT or PET. Patients with Parkinson's disease respond to levodopa or dopaminagonists throughout the course of the disease. Parkinson's disease is also characterised by various vegetative symptoms, impairment of olfaction, anxiety, depression, and with increasing age also by cognitive deficits and dementia.

[The role of dopaminagonists in the treatment of Parkinson's disease]. / Stellenwert der Dopaminagonisten in der Parkinson-behandlung.

Dopamine agonists play an important role in the treatment of early Parkinson's disease, either as monotherapy or in combination with levodopa. Initial treatment with dopamine agonists has been found to postpone or prevent from motor fluctuations and dyskinesias. Dopamine agonists have also been shown to be significantly effective in the treatment of motor oscillations and dyskinesias related to chronic levodopa treatment. The "new" dopaminagonists pergolide, cabergoline, ropinirole and pramipexole tend to be more effective than bromocriptine. Due to side-effects dopamine agonists are mainly used in subjects younger than 70 to 75 years.

Internal carotid artery stent placement without emboli protection: results and long-term outcome.

Patients with symptomatic > or = 60% (n = 134), asymptomatic > or = 80% (n = 143), and asymptomatic progressive > or = 60% (n = 25) internal carotid artery stenosis underwent stenting and were followed clinically and by Doppler-assisted duplex imaging for 27.1 +/- 15.6 months. Stroke and death from stroke occurred within 30 days after stenting in 4.7% of the symptomatic and in 3.0% of the asymptomatic patients and in the follow-up period in 2.3% of the symptomatic and in 1.2% of the asymptomatic patients.

CADASIL-an unusual manifestation with prominent cutaneous involvement.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucencephalopathy (CADASIL) is a rare vascular disorder affecting mainly the central nervous system with transient ischaemic attacks, strokes, psychiatric symptoms and dementia. It is a progressive familial disease owing to mutations in the Notch3 gene. Clinically apparent skin involvement is usually absent. Electron microscopy of seemingly uninvolved skin reveals characteristic granular deposits in the basal lamina of vessels and adnexals. We report on a case of CADASIL with generalized haemorrhagic macules and patches. Typical neurological symptoms as well as classical findings in histopathology and electron microscopy confirmed the diagnosis. Immunofluorescence showed an increased number of vessels with walls markedly thickened by deposits of fibrin, complement and immunoglobulins. This method could serve as an additional method for accurate diagnosis of CADASIL.

The role of alpha-synuclein gene multiplications in early-onset Parkinson's disease and dementia with Lewy bodies.

BACKGROUND: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families. METHOD: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe. RESULTS: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein. Mutational screening of the entire coding region of alpha-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case. CONCLUSIONS: Thus, this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.

L-dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia.

The authors analyzed whether nondemented (PD) and demented Parkinson patients (PDD) and patients with dementia with Lewy bodies (DLB) respond similarly in the levodopa test (LDT). Percentage of motor improvement was similar in the three groups; the proportion of patients with 10% and more improvement was greater in PD than in PDD and DLB. Positive LDT was predictive for favorable response in chronic levodopa treatment, but also some nonresponsive demented patients profited from chronic levodopa therapy.

Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1).

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). After a traumatic brain injury depositions of amyloid beta (Abeta) in the brain parenchyma were found. In this study we investigated the expression pattern of beta-secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats. BACE-1 mRNA levels, estimated by real time RT-PCR, were elevated 24 h post injury, and persisting up to 72 h, in the ipsi- and contralateral hippocampus and cerebral cortex as compared to the sham-treated animals (p<0.01). The TBI-induced changes in BACE-1 mRNA are due to enhanced hippocampal and cortical expression of BACE-1 mRNA in neurons and reactive astrocytes as revealed by in situ hybridization. The alterations in hippocampal BACE-1 mRNA levels are accompanied by corresponding increases in BACE-1 protein levels in ipsi- and contralateral hippocampus and ipsilateral cortex as demonstrated by Western blot analysis. In contrast, in the contralateral cortex only a weak increase of traumatically induced BACE-1 protein production was found. The activity of BACE-1 as measured by the formation of the cleavage product of amyloid beta precursor protein, transiently increased up to 48 h after injury, but returned to basal level 7 days post injury. This study demonstrates that the beta-secretase is stimulated following TBI and may suggest a mechanism for the temporal increase of Abeta levels observed in patients with brain trauma.

Unaltered brain levels of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal in Alzheimer's disease.

In recent years, an important role for the pathogenesis of Alzheimer's disease (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product of lipid peroxidation, forms stable adducts with a variety of nucleophilic substituents such as thiols or amino moieties. Here, we report the quantification of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp) using the specific and very sensitive method of 32P-postlabeling of deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the hippocampus, the parietal cortex, and the cerebellum of postmortem brains from patients with AD and age matched controls. Adduct levels were highest in the hippocampus, followed by the cerebellum and parietal cortex irrespective of the disease. Neither age, postmortem delay time, gender, nor the extent of neurofibrillary deposits affected tissue adduct levels in the brain areas examined. Although distinctively present in the human brain, the level of HNE-dGp adducts appears not to be useful as a biomarker for AD.

[Dysequilibrium in idiopathic Parkinson disease. The effect of cerebrovascular comorbidity]. / Gleichgewichtsstörungen bei idiopathischer Parkinson-Erkrankung. Der Einfluss zerebrovaskulärer Komorbidität.

Disturbance of balance in idiopathic Parkinson's disease (IPD) has a significant effect on disability. Yet the underlying mechanisms and the contribution of age-associated comorbidity to dysequilibrium are unclear. In this study, static posturography was performed in 30 healthy controls and 40 patients with IPD. Comparison of sway during quiet stance did not show significant differences between patients and controls. Multiple linear regression analysis was used to identify factors responsible for the considerable interindividual variance in patients. Results of the pull test, CT-verified cerebral microangiopathy, dementia, and age were assessed, but only cerebrovascular comorbidity contributed significantly to variance. Apart from increased sway, patients with coinciding cerebral microangiopathy (n = 20) more frequently had a history of falls or pathological responses in the pull test. The present results suggest that cerebrovascular comorbidity enhances dysequilibrium in IPD. Pathological sway in IPD can indicate comorbidity and may have implications for further diagnostics.

[Dementia with Lewy bodies]. / Demenz mit Lewy-Körperchen.

Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, Parkinson syndrome, fluctuations of cognitive functions, vigilance and attention, visual hallucinations (usually detailed and well described), depression, REM-sleep behavior disorder, adverse responses to standard doses of neuroleptics, falls, syncopes, systematized delusions, and non-visual hallucinations. Mean age at disease onset ranges between 60 and 68 years. Male persons are more frequently affected than female. Disease duration is six to seven 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, in rare cases, Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha-receptor-blocking medicaments to improve neurogenic bladder dysfunction.

Dystonia in multiple system atrophy.

OBJECTIVE: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA). METHODS: A cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6-12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients. RESULTS: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5-4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient. CONCLUSION: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA.

Ibuprofen decreases cytokine-induced amyloid beta production in neuronal cells.

Trying to decrease the production of Amyloid beta (Abeta) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFalpha with IFNgamma induces the production of Abeta-42 and Abeta-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFalpha and IFNgamma. Ibuprofen treatment decreased the secretion of total Abeta in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Abeta-42 and Abeta-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Abeta by ibuprofen was presumably due to a decreased production of betaAPP, which in contrast to the control proteins M2 pyruvate kinase, beta-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.

Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study.

Sporadic amyotrophic lateral sclerosis (sALS) is a neurodegenerative disorder of unknown cause characterized by selective loss of both upper and lower motor neurons. Whether neuronal death in sALS is due to apoptosis has so far not been clarified. In this study, the expression and distribution patterns of pro- and anti-apoptotic bcl-2 family members as well as the executioner caspase-3 were investigated in post-mortem CNS tissue of eight sALS patients and seven age-matched controls. Sparse motor neurons were immunoreactive for bcl-2, bax, bak, and CM1 on serial sections through the spinal cord and motor cortex of individual sALS patients and controls. However, there was no obvious difference in the numbers of immunoreactive (IR) neurons between the two groups. The study did not find evidence for apoptosis as a major mechanism of motor neuronal cell death in sALS.