Clinical Neuroscience


ZÁDORI Dénes, DATKI Zsolt, PENKE Botond

NOVEMBER 30, 2007

Clinical Neuroscience - 2007;60(11-12)

[In Alzheimer’s disease, which belongs to the neurodegenerative disorders, the ethiopathogenetic role of several risk factors has been proved. A considerable number of them are mainly known as cardiovascular risk factors and can precipitate chronic brain hypoperfusion. Using functional imaging techniques, this hypoperfusion and the resulting hypometabolism become detectable in the watershed areas of the brain as early as in the stage of mild cognitive impairment. Hypoperfusion leads to the degeneration of capillaries in this area causing the deterioration of diffusion. The further reduction of nutrient and oxygen support of neurons is capable to initiate a neurodegenerative process which spreads along the glutamaterg system arising from the neurons of the association cortices. The neuropathological lesions of this neuronal system, such as the neurofibrillary tangles and the β-amyloid plaques, are known to be the characteristic markers of Alzheimer's disease. In our review we present the development of hypoperfusion and its consequences in the watershed areas of the brain and describe the neurodegenerative process of the neuronal system arising from the neurons of the association cortices in the early stage of Alzheimer's disease. Considering the previous hypotheses and the neuropathological lesions of Alzheimer's disease we give a new consensus model to characterize the pathomechanism of the disorder.]



Further articles in this publication

Clinical Neuroscience


AUER Tibor, SCHWARCZ Attila, EZER Erzsébet, CZEITER Endre, ARADI Mihály, HUDVÁGNER Sándor, JANSZKY József, BÜKI András, DÓCZI Tamás

[Aim of the study - Presentation of diffusion tensor imaging (DTI) performed at low magnetic field (1 Tesla) in the algorithm of work-up of a patient suffering from severe traumatic brain injury (TBI). Method - DTI and functional MRI (fMRI) were applied at 1 Tesla for visualization of neural pathways and examination of sensory functions of a patient with severe TBI. DTI-measurement was also performed on a healthy patient for comparison. Results - DTI acquired at low magnetic field yielded appropriate visualization of neural pathways. DTI confirmed the results of the clinical and fMRI examinations in the patient suffering from severe TBI. Conclusion - An optimized DTI can be useful in the examination of patients with TBI, moreover, it may also help in the establishment of diagnoses of other central nervous system diseases affecting neuronal pathways. The presented results suggest that DTI of appropriate quality can be performed at low magnetic field.]

Clinical Neuroscience


VARGA Edina Tímea, ELIF Kaya, ANTAL Andrea, ZIMMER Márta, HARZA Irén, WALTER Paulus, KOVÁCS Gyula

[Previous studies have observed that prolonged adaptation to a face will bias the perception of a subsequent one. This phenomenon is known as figural or face after-effect. Although currently the topic of face adaptation enjoys utmost popularity, we still don't know much about the neural process underlying it. The aim of the present study was to determine, using transcranial direct current stimulation (tDCS), how the retinotopically organised primary visual cortex (V1) and higher-level, non-retinotopic right lateral temporo-parietal areas interact with facial adaptation processing. Seventeen healthy subjects recieved 10 min anodal, cathodal or sham stimulation over these areas during a facial adaptation task. Cathodal stimulation of the right temporo-parietal cortex reduces the magnitude of facial adaptation while stimulation over the V1 results in no significant effects. These data imply that mainly lateral temporo-parietal cortical areas play role in facial adaptation and in facial gender discrimination, supporting the idea that the observed after-effects are the result of high-level, configurational adaptation mechanisms.]

Clinical Neuroscience


KAREN Eskesen, TAJTI János, HORTOBÁGYI Tibor, SZOK Délia, VÉCSEI László, LARS Edvinsson

[Calcitonin-like receptor (CL-R) is a functional CGRP1- receptor when complexed with RAMP1 or an adrenomedullin-receptor or when complexed with RAMP2 or RAMP3. This study was carried out 1. to set up a method to examine the relative quantity of mRNA of CL-R, RAMP1, RAMP2 and RAMP3 in human coronary (CA), pulmonary (PA) and middle cerebral arteries (MCA), and 2. to examine the level of mRNA expression in cerebro- and cardiovascular diseases. The method was validated with respect to the use of postmortem tissue and we compared β-actin and GAPDH as housekeeping genes. There was no time-dependent change in total RNA and level of mRNA for β-actin or GAPDH could be detected in vessels removed from 1 and 5 days post mortem. The expression of β-actin appears lower in coronary artery than in pulmonary artery and middle cerebral artery with no significant difference for GAPDH; both worked well. There were some differences in mRNA expression for CL-R (higher) and RAMP3 (lower) in middle cerebral artery compared to coronary artery and pulmonary artery. There was no significant difference in mRNA for RAMP1 and RAMP2 in the three types of arteries. We did not observe any difference in mRNA for CL-R and RAMPs in arteries from patients with hemorrhagic stroke, arteriosclerosis and acute myocardial infarction when compared to patients without these diagnoses. Thus the mRNA expression seems to be unaltered in these disorders.]

Clinical Neuroscience


Clinical Neuroscience


KOVÁCS Gábor Géza

[acquired. The human prion protein gene (PRNP) is located to chromosome 20 (20p12-ter). Mutations and polymorphisms in the PRNP are associated with prion disease. Genetic prion diseases are inherited in an autosomal dominant trait, examination of the penetrance is restricted to mutation E200K (59-89%). Mutations can be substitutions or insertions. Genetic prion diseases are classified according to the clinicopathological phenotype and comprise genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia. Base pair insertions may resemble Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker disease phenotypes, however, their unique clinicopathological presentations are also emphasized. Among the polymorphisms of the PRNP, the one at codon 129 is the most important, where methionine or valine may be encoded. This polymorphism is known to influence the phenotype of disease forms. Molecular classification of sporadic Creutzfeldt-Jakob disease also depends on the codon 129 polymorphisms in addition to the Western blot pattern of the protease resistant prion protein. According to this at least six well characterised forms of sporadic Creutzfeldt-Jakob disease are known. Influence of other genes were also investigated. Contrasting results are reported regarding the role of apolipoprotein E allele ε4, but presence of allele ε2 seems to influence the prognosis. Polymorphisms in the doppel gene or ADAM10 could not be clearly associated with Creutzfeldt-Jakob disease. Polymorphisms in the upstream and intronic regulatory region of the PRNP gene may be a risk factor for Creutzfeldt-Jakob disease. The PRNP codon 129 polymorphism was examined in non-prion diseases. Some studies suggest that this polymorphism may have influence on the cognitive decline and early onset Alzheimer’s disease.]

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Clinical Neuroscience



[Out of an average total of 1400 autopsies per year, neuropathological examinations were performed in 477 cases between 1997 and 1999 to investigate the incidence of dementias. The majority of the studied subjects were over 50 years old. Bielschowsky's and/or Gallyas's silver methods and, in some cases, protein tau (MAP) immuncytochemistry and amyloid staining were performed beside routine examination. Pathological changes were found in 212 of the 364 cases studied by the above methods but histological changes associated with dementia were only detected in 167 cases. The various forms of Alzheimer's dementia were also classified by age. The "incipient" form of Alzheimer's disease was verified in 23 cases. Old infarcts of various extensions were found in 42 percent of Alzheimer's dementias. Very mild or age-related degenerative changes were observed in 82 cases among subjects over 50 years old. Of these, eight patients died in their 90s. In some cases (n=38) the number of neuritic plaques dominated over the number of neurofibrillary tangles but a reverse finding also occurred (n=13). Neuronal degeneration was variable and was not always proportional to the number of neurofibrillary tangles. "Simple type of senile atrophy" was defined by the presence of minor or age-related Alzheimer changes and was considered a separate entity. The "incipient" form of Alzheimer's dementia was diagnosed in relatively young individuals where mild Alzheimer changes were found at the neuropathological examination. "Preclinical" Alzheimer's dementia could only be suspected by clinical data and could very rarely be supported by the neuropathological finding of "incipient" form. The ratio of pure Alzheimer’s to vascular dementias cases proved to be 54:41 in this study. The results suggest that dementias are considerably underdiagnosed both in the clinical and pathological practice and that the recently defined "preclinical" and "incipient" forms are very hard to recognize both clinically and pathologically. The neuropathological study of the degenerative, mainly Alzheimer's type, findings in the randomly selected autopsies revealed great variations which raises many questions concerning the normal and pathologic aging of the brain as well as the "incipient" and senile forms of Alzheimer's dementia.]

Clinical Neuroscience


KOVÁCS Á. Katalin, PÁMER Zsuzsanna, KOVÁCS Attila, FEKETE Sándor, MISETA Attila, KOVÁCS Bálint, KOVÁCS L. Gábor

[Background - Age-related macular degeneration (AMD) and Alzheimer dementia (AD) show similarities (advanced age, formation of deposits of similar content). Recently apolipoprotein E 2 (apoE 2) has been associated with AMD, while apoE4 with AD. The question of coexistence, especially with respect to the genetic background has not been studied earlier. We investigated, therefore, the occurrence of AMD in AD patients and compared their lipid profile and apoE polymorphism. Methods - 49 AMD, 32 AD and 27 control patients were examined (risk factors, visual acuity, slit lamp biomicroscopy, fundoscopy). Following measurement of triglyceride, total and HDL cholesterol levels, apoE mutation analysis was performed. Results - AMD was found in 8% of the cooperating AD patients. The prevalence of the apoE 4 isoforms in the AMD, AD and the control patients was 2%, 47% and 22%, while that of apoE 2 was 17%, 6% and 7%, respectively. The prevalence of apoE 3 isoform was 82%, 41% and 71%, respectively. Triglyceride, total and HDL cholesterol were in the reference range; however, AD patients were characterized by a lower total cholesterol value. Conclusions - The new finding of this publication is the rare occurrence of AMD among AD patients. The higher frequency of apoE 4 among the AD population, and the higher frequency of apoE 2 among AMD patients in the South-Western region of Hungary confirms the findings of other investigators.]

Lege Artis Medicinae

[Pharmacotherapy of dementia ]

PÁKÁSKI Magdolna, KÁLMÁN János

[The goal of treatment of dementia-related disorders is to reserve cognitive and functional ability, minimize behavioral and psychological disturbances, and slow disease progression, since currently available therapies can not reverse the pathologic processes. Among them, the most common is Alzheimer’s disease and vascular dementia. The authors review the therapeutic guidelines of these dementia types adapted to Hungarian conditions. Cho­li­nesterase inhibitors represent first-line therapy for patients with mild to moderate Alzheimer’s disease, whereas a glutamate N-metil-D-aspartate antagonist is used in the treatment of moderate to severe Alzheimer’s disease. In milder stages, phar­macotherapy may be supplemented by the use of nootropics. The progression slowing drugs have not only impact on cognitive symptoms but also affect behavioral and psychological symptoms. De­pen­ding on the severity of dementia and the existence of behavioral and psychological symptoms, these medicines may be re­commended as monotherapy or in combination. To further alleviate behavioral and psychological symptoms a variety non-pharmacological methods are known, at present their effectiveness has not been proven. Antipsychotics may be used to reduce agitation and aggression. Taking into account the side effects profile of antipsychotics, tiapride or risperidon ad­mi­nistration can be considered. In the case of their ineffectiveness, haloperidol may be used. ]

Clinical Neuroscience

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and β-actin genes in rat brain]

KÁLMÁN János, PÁKÁSKI Magdolna, SZŰCS Szabina, KÁLMÁN Sára, FAZEKAS Örsike, SÁNTHA Petra, SZABÓ Gyula, JANKA Zoltán

[Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer’s disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations - also affecting the metabolism of β-actin - can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], β-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n=16), CIS (n=10), 10 mg/kg sertindole (n=5) and 10 mg/kg sertindole + CIS (n=4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal β-actin (p<0.01), MAPK-1 and APP (p<0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p<0.05). Ours is the first report about CIS induced β-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.]

Clinical Neuroscience

[Epidemiology of dementia in Hungary]

ÉRSEK Katalin, KÁRPÁTI Krisztián, KOVÁCS Tibor, CSILLIK Gabriella, GULÁCSI L. Ádám, GULÁCSI László

[Objective - To estimate the epidemiology and the distribution of disease severity of dementia in Hungary, using published data. To estimate the demented population of 2008 and to make a projection for 2050. Methodology - With an outlook for the international professional literature and the available Hungarian information we examine the epidemiology of dementia in Hungary by age-groups and disease severity (according to MMSE categories), then make our estimation for the entire population. Results - Based on the estimation of the number of demented people in Hungary there is a noticeable difference between the domestic and the internationally published data. According to previous Hungarian studies, the number of the demented subjects vary between 530 and 917 thousand patients. Multiplying the elderly age-group’s populations by the global prevalence data it results in 101 thousand of demented patients. Estimation by the domestic published data we remarkably overestimate the presumed value, whereas by using the global prevalence figures we underestimate. Conclusions - There is a strong need for a representative study to obtain exact figures on the prevalence of dementia in Hungary. Getting exact figures of the Hungarian prevalence of dementia it is a strong need an overall representative study. With the lack of it the health and social care systems are not able to prepare for providing the increasing number of patients.]