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Galariotis V, Bódi N, Janka Z, Kálmán J. · University of Szeged, Department of Psychiatry, Szeged. · Ideggyogy Sz. · Pubmed #16173270 No free full text.

Abstract: This is a comprehensive paper in three parts covering history, prevalence, clinical forms, differential diagnosis, genetics, molecular pathomechanism, pathology, clinical diagnosis and treatment of frontotemporal dementia (FTD). The second part focuses on the differential diagnosis, genetics, molecular pathomechanism and pathology. The clinical diagnosis of frontotemporal dementia is based on the presence of a prominent disturbance of the executive function and of frontal lobe syndrome or a progressive aphasic syndrome without severe global cognitive impairment. Of other dementias, it is primarily Alzheimer's disease that it should be differentiated from, but other psychiatric disorders must also be ruled out. The disease has familial and sporadic forms. Recent identification of mutations in the gene encoding the microtubule-associated tau protein in the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has demonstrated that various tau dysfunctions can lead to neurodegeneration. Tau gene mutations have varied effects on the biology and function of the protein. This heterogeneous pathomechanism explains the wide range of clinical and neuropathological features observed in the FTDP-17. Tau and ubiquitin antibodies can be detected by sensitive immunohistochemical methods. The diagnosis of FTD should be based on neuropathological examination, and this is also the only method by which it can be definitely differentiated from other types of dementias.

Galariotis V, Bódi N, Janka Z, Kálmán J. · University of Szeged, Department of Psychiatry, Szeged. · Ideggyogy Sz. · Pubmed #16021963 No free full text.

Abstract: The authors report a comprehensive publication consisting of three parts going into the details of history, prevalence, clinical forms, differential diagnosis, genetics, molecular pathomechanism, pathology, clinical diagnosis and treatment of frontotemporal dementia (FTD). The first part of the present review deals with history, prevalence and clinical forms of FTD. The prototypical FTD with circumscribed atrophy was first described by Arnold Pick; Alois Alzheimer found the intraneural inclusions in the patients' brain. Later it was recognised that many patients had neither the atrophy nor the cellular changes, but genetic mutations have been identified. Frontotemporal dementia is a degenerative condition with unknown etiology in the frontal and anterior temporal lobes of the brain. It is a progressive neurobehavioral syndrome characterized by early decline in social interpersonal conduct, early impairment in the regulation of personal conduct, early emotional blunting, and early loss of insight. There are no reliable epidemiological studies on the prevalence of FTD, but it is well-accepted that FTD is a common cause for dementia before the age of 65 (it constitutes approximately five percent of all irreversible dementias). The nomenclature of the FTD has been confusing and continues to be. Three major clinical syndromes can be identified: 1 frontal variant FTD (dementia of frontal type) in which changes in social behavior and personality predominate, 2. in semantic dementia (progressive fluent aphasia) there is a breakdown in the conceptual database which underlies language production and comprehension, 3. in progressive nonfluent aphasia the phonologic and syntactic components of language are affected. The authors report two cases, which can point to clinical symptoms and forms, and mention the problems of the differential diagnosis and therapy.

Kálmán J, Palotás A, Bódi N, Kincses TZ, Benedek G, Janka Z, Antal A. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. · Brain Res Bull. · Pubmed #15862926 No free full text.

Abstract: Impaired neuronal energy metabolism, oxidative changes and microvascular abnormalities lead to altered lactate levels in Alzheimer's dementia. The aim of the present study was to assess whether intravenous sodium-lactate, a metabolic alternative and vasodilator that is thought to improve cognition, advances the cognitive performance of Alzheimer patients. Semantic categorization paradigm was used to present the electrophysiological correlates of natural scene categorization of Alzheimer patients before and after intravenous saline or sodium-lactate infusion. Mean amplitudes of event-related potentials (ERPs) were measured in two time windows before and after the treatments; two negative components (N1 between 150 and 250 ms and N2 between 400 and 600 ms) and one positive component (P2 between 250 and 400 ms) were identified. The negative components were more negative for the non-animal trials than for the animal trials while the positive component was similar for both categories. After the lactate treatment the amplitudes of the negative components became more negative mainly for the non-animal trials while the amplitude of the positive component turned more positive for the animal trials, however these changes were not significant. No changes have been observed after normal saline infusion. These results suggest that, contrary to its anticipated beneficial effects, sodium-lactate fails to significantly improve semantic categorization processes in Alzheimer's disease and this enhancement can be detected by recording ERPs. The effect of sodium-lactate to slightly improve semantic memory might be based on its positive effect on cardio- and cerebro-vascular function and neuronal metabolism.

Bódi N, Csibri E, Myers CE, Gluck MA, Kéri S. · Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary. · Cogn Behav Neurol. · Pubmed #19506424 No free full text.

Abstract: BACKGROUND: Acquired equivalence is a phenomenon in which prior training to treat 2 stimuli as equivalent increases generalization between them. Previous studies demonstrated that the hippocampal complex might play an important role in acquired equivalence associative learning. In this study, we tested the possibility that acquired equivalence learning is a sensitive marker of mild Alzheimer disease (AD). METHODS: In the associative learning test, antecedent stimuli were cartoon faces and consequent stimuli were different colored cartoon fishes. Each cartoon character had some pet fish and the task was to learn these face-fish associations using feedback provided after each decision. In the transfer phase, knowledge about face-fish pairs had to be generalized to new associations. RESULTS: AD patients exhibited mild impairments in the training phase, whereas they were profoundly impaired on the acquired equivalence test. Associative knowledge could not be transferred to a more flexible retrieval condition. CONCLUSIONS: These results suggest that acquired equivalence learning is specifically impaired in early AD, which may indicate the pathology of the hippocampal complex.

Juhász A, Rimanóczy A, Boda K, Vincze G, Szlávik G, Zana M, Bjelik A, Pákáski M, Bódi N, Palotás A, Janka Z, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary. · Neurochem Res. · Pubmed #16258842 No free full text.

Abstract: Multiple genetic and environmental factors regulate the susceptibility to Alzheimer's disease (AD). Recently, several independent studies have reported that a locus on chromosome 14q32.1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD. The single nucleotide polymorphism (T/C) in intron 2 of CYP46 gene has been found to confer the risk for AD. The water soluble 24(S)-hydroxysterol is the product of the CYP46A1, and elevated plasma and cerebrospinal fluid hydroxysterol concentrations have been found in AD, reflecting increased brain cholesterol turnover or cellular degradation, due to the neurodegenerative process. A case-control study was performed on 125 AD and 102 age- and gender-matched control subjects (CNT) from Hungary, to test the association of CYP46 T/C and apolipoprotein E (ApoE) gene polymorphisms in AD. The frequency of the CYP46 C allele was similar (chi2=0.647, df=1, P=0.421, exact P=0.466, OR=0.845; 95% CI: 0.561-1.274) in both groups (CNT: 27%; 95% CI: 21.3-33.4; AD 30%; 95% CI: 25.0-36.3). The ApoE varepsilon4 allele was significantly over-represented (chi2=11.029, df=2, P=0.004) in the AD population (23.2%; 95% CI: 18.2-29.0) when compared with the CNT (11.3%; 95% CI: 7.4-16.6). The presence or absence of one or two CYP46C alleles together with the ApoE varepsilon4 allele did not increase the risk of AD (OR=3.492; 95% CI: 1.401-8.707; P<0.007 and OR=3.714; 95% CI: 1.549-8.908; P<0.003, respectively). Our results indicate that the intron 2 T/C polymorphism of CYP46 gene (neither alone, nor together with the varepsilon4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.

Juhász A, Palotás A, Janka Z, Rimanóczy A, Palotás M, Bódi N, Boda K, Zana M, Vincze G, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Semmelweis u 6, H-6721, Szeged, Hungary. · Neurochem Res. · Pubmed #16176061 No free full text.

Abstract: Apolipoprotein E gene (Apo(epsilon)) has three common alleles (epsilon2, epsilon3, and epsilon4), of which epsilon4 has been shown to be associated with an increased risk for Alzheimer's disease (AD). Possible additional genetic factors, like the -491A variant of ApoE promoter may modify the development of AD, independently of the ApoE allele status. The objective of this study was to investigate whether A/T allelic polymorphism at site-491 of the ApoE promoter is associated with AD in a Hungarian population. The genomic DNA isolated from peripheral blood lymphocytes of 52 late-onset AD and 53 control individuals was used as a template for the two examined polymorphisms and PCR assay was applied. The epsilon4 allele was significantly over-represented in the AD group (28%) as compared with the control population (7%). No significant differences have been found between the control and the AD populations regarding the occurrence of the promoter A allele frequencies (control: 77%, AD: 70%). However, the AA genotype was more frequent in the AD group (48%) than in the control (10%) when the presence of epsilon4 allele was also considered. It is unlikely therefore that the -491A variant of the ApoE promoter gene is an independent risk factor in the Hungarian AD population, but a linkage disequilibrium exists between the two examined mutations.