[Movement disorders is psychiatric diseases]. / Mozgászavarok pszichiátriai betegségekben.

Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.

[Pharmacological and other options in preventing dementia: a literature review]. / Demenciák megelozésének gyógyszeres és egyéb lehetoségei: irodalmi összefoglaló

BACKGROUND: At present 34 million people live with Alzheimer's disease around the world. This figure is expected to triple in the next 40 years. The major cause of this increase is the well-known aging of the society in Europe and in the US as well. AIMS AND METHODS: In this paper we review the results of the last 10 years, and discuss those pharmaceutical and other methods, which can be effective in the prevention of dementias. RESULTS: The most important pharmaceutical agents are beta secretase inhibitors, and active and passive immunizations. Several drugs in these groups are in phase III at the moment. The results from studies with intranasal insulin are also encouraging. As a non-drug option Mediterranean diet can be effective. However at present cognitive trainings seem to be the most effective in the prevention of dementias. These remediation therapies are based on the lifelong plasticity of the human brain. CONCLUSIONS: In summary we can conclude that there are promising drug developments in progess for the prevention of dementias, but the breakthrough has not been achieved yet. At present the best option is decreasing risk factors, that is treatment of hypertension, prevention of obesity and diabetes, and cognitive trainings are recommended for prevention.

Low Functional network integrity in cognitively unimpaired and MCI subjects with depressive symptoms: results from a multi-center fMRI study.

Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salience Network, and the Cognitive Control Network. All 183 elderly subjects underwent a comprehensive neuropsychological evaluation and a 3 Tesla brain MRI scan. To assess the potential presence of depressive symptoms, the 13-item version of the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) was utilized. Participants were assigned into three groups based on their cognitive status: amnestic mild cognitive impairment (MCI), non-amnestic MCI, and healthy controls. Regarding affective symptoms, subjects were categorized into depressed and non-depressed groups. An increased mean eccentricity and network diameter were found in patients with depressive symptoms relative to non-depressed ones, and both measures showed correlations with depressive symptom severity. In patients with depressive symptoms, a functional hypoconnectivity was detected between the Anterior Cingulate Cortex (ACC) and the right amygdala in the FLN, which impairment correlated with depressive symptom severity. While no structural difference was found in subjects with depressive symptoms, the volume of the hippocampus and the thickness of the precuneus and the entorhinal cortex were decreased in subjects with MCI, especially in amnestic MCI. The increase in eccentricity and diameter indicates a more path-like functional network configuration that may lead to an impaired functional integration in depression, a possible cause of depressive symptomatology in the elderly.

Theta-burst rTMS in schizophrenia to ameliorate negative and cognitive symptoms: study protocol for a double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Treatment effects of conventional approaches with antipsychotics or psychosocial interventions are limited when it comes to reducing negative and cognitive symptoms in schizophrenia. While there is emerging clinical evidence that new, augmented protocols based on theta-burst stimulation can increase rTMS efficacy dramatically in depression, data on similar augmented therapies are limited in schizophrenia. The different patterns of network impairments in subjects may underlie that some but not all patients responded to given stimulation locations. METHODS: Therefore, we propose an augmented theta-burst stimulation protocol in schizophrenia by stimulating both locations connected to negative symptoms: (1) the left dorsolateral prefrontal cortex (DLPFC), and (2) the vermis of the cerebellum. Ninety subjects with schizophrenia presenting negative symptoms and aging between 18 and 55 years will be randomized to active and sham stimulation in a 1:1 ratio. The TBS parameters we adopted follow the standard TBS protocols, with 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 100% active motor threshold. We plan to deliver 1800 stimuli to the left DLPFC and 1800 stimuli to the vermis daily in two 9.5-min blocks for 4 weeks. The primary endpoint is the change in negative symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Secondary efficacy endpoints are changes in cognitive flexibility, executive functioning, short-term memory, social cognition, and facial emotion recognition. The difference between study groups will be analyzed by a linear mixed model analysis with the difference relative to baseline in efficacy variables as the dependent variable and treatment group, visit, and treatment-by-visit interaction as independent variables. The safety outcome is the number of serious adverse events. DISCUSSION: This is a double-blind, sham-controlled, randomized medical device study to assess the efficacy and safety of an augmented theta-burst rTMS treatment in schizophrenia. We hypothesize that social cognition and negative symptoms of patients on active therapy will improve significantly compared to patients on sham treatment. TRIAL REGISTRATION: The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT05100888. All items from the World Health Organization Trial Registration Data Set are registered. Initial release: 10/19/2021.

[Differentiation between mild cognitive impairment and healthy elderly population using neuropsychological tests]. / Az enyhe kognitív deficitben szenvedok differenciálása az egészséges idos populációtól neuropszichológiai tesztek segítségével.

OBJECTIVE: Paired Associates Learning (PAL) test assesses brain functions in those brain regions affected earliest by Alzheimer's dementia. The aim of the present study was to assess the usability of our implementation of the PAL test for screening mild cognitive impairment. METHODOLOGY: Based on Petersen criteria, 14 out of the 63 subjects were diagnosed with mild cognitive impairment. Visuospatial learning was assessed by our implementation of PAL test. The ability of the PAL test to differentiate between study groups was compared to the Addenbrook Cognitive Examination (ACE) and to the Mini Mental State Examination (MMSE). Linear logistic regression was used for statistical analysis, and the results are presented as Receiver Operating Characteristics (ROC) curves. All analyses were performed by SAS 9.2. RESULTS: All the results of neuropsychological tests differed significantly between the study groups. However, considerable difference could be detected between the tests regarding specificity and sensitivity. The PAL test reached the sensitivity of the ACE, while its specificity was slightly under the ACE. DISCUSSION: The PAL test developed in the framework of the present study is found to be able to differentiate between MCI and healthy controls. It outperformed the MMSE in terms of sensitivity and specificity, while it needs comparable time to perform. Its sensitivity, the important parameter for screening, is comparable to ACE, while it needs significantly shorter time and less assistance.

[Efficacy of deep brain stimulation in our patients with Parkinson's disease]. / A mély agyi stimuláció hatékonysaga Parkinson- kóros betegeink kezelésében.

BACKGROUND AND PURPOSES: In advanced Parkinson's disease, medically refractory motor fluctuation or medically resistant tremor considerably affects quality of life. However, these symptoms can be mostly successfully treated by deep brain stimulation. We analyzed the efficacy of bilateral subthalamic stimulation in our patients with Parkinson's disease. METHODS: We assessed the clinical data of ten patients who have been treated in the Department of Neurology, Semmelweis University and have been operated in the National Institute of Neurosciences between 2008 and 2011. The Hoehn-Yahr scale score, the Unified Parkinson's Disease Rating Scale score and the Parkinson's Disease Questionnaire 39, as well as the dose of antiparkinson medication were documented prior to and one year after surgery. RESULTS: Patient condition improved according to the Hoehn-Yahr scale, approximately by two stages. The dose of antiparkinson medication could be reduced by 63.4% (p = 0.005) post operation. Unified Parkinson's Disease Rating Scale scores decreased by 70.9% (p = 0.005). 12 hours after medication withdrawal, execution of daily activity improved by 57.1% (p < 0.01) and motor functions developed by 79.1% (p < 0.01). Duration of dyskinesias decreased by 62.5% (p = 0.018), duration of akinesia diminished by 87.5% (p = 0.005). Quality of life rose by 41.6% (p < 0.01). Neuropsychological tests detected improvement in verbal memory. CONCLUSION: With deep brain stimulation, the dosage of antiparkinson medication could be significantly reduced, with considerable improvements in motor function and quality of life. Although the number of patients is still low, good results have been established by careful patient selection, precise neurosurgical procedure and by appropriate programming and patient care.

Comparison of the diagnostic accuracy of resting-state fMRI driven machine learning algorithms in the detection of mild cognitive impairment.

Mild cognitive impairment (MCI) is a potential therapeutic window in the prevention of dementia; however, automated detection of early cognitive deterioration is an unresolved issue. The aim of our study was to compare various classification approaches to differentiate MCI patients from healthy controls, based on rs-fMRI data, using machine learning (ML) algorithms. Own dataset (from two centers) and ADNI database were used during the analysis. Three fMRI parameters were applied in five feature selection algorithms: local correlation, intrinsic connectivity, and fractional amplitude of low frequency fluctuations. Support vector machine (SVM) and random forest (RF) methods were applied for classification. We achieved a relatively wide range of 78-87% accuracy for the various feature selection methods with SVM combining the three rs-fMRI parameters. In the ADNI datasets case we can also see even 90% accuracy scores. RF provided a more harmonized result among the feature selection algorithms in both datasets with 80-84% accuracy for our local and 74-82% for the ADNI database. Despite some lower performance metrics of some algorithms, most of the results were positive and could be seen in two unrelated datasets which increase the validity of our methods. Our results highlight the potential of ML-based fMRI applications for automated diagnostic techniques to recognize MCI patients.

[Depression in neuropsychiatric diseases]. / Depresszió neuropszichiátriai betegségekben.

Depression is frequently observed together with neurological disorders. Moreover this connection is bidirectional in the case of several neurological disorders, as depression can be either a comorbide syndrome or also a risk factor of them. Neurobiological background of depression involves neuroanatomical structures, their interconnected networks, disturbances of neurotransmitters, neurohormonal, neuroimmunological and neurotrophic changes, genetic background. Disfunction of these systems also plays a role in the pathogenesis of comorbid depression of neurological disorders. Interactions and clinical aspects of biological factors involved in the pathogenesis of depression in dementias, Parkinson's disease, cerebrovascular disorders and epilepsy are discussed further. Depression as a result of neurobiological factors responsible for both neurological and psychiatric consequencies of these disorders, are often atypical as a clinical manifestation, however chracteristic for the particular neurological disorder. Evaluation of the biological backgound and clinical features of depression in neurological disorders makes the complex neuropsychiatric approach of these disorders possible.

[Neurological symptoms in psychiatry]. / Neurológiai tünetek a pszichiátriában.

Certain psychiatric diseases have biological pathomechanisms, and as a result they are accompanied by various neurological symptoms. Neurological examination is a simple method to assess these symptoms. Neurological signs come in two varieties; they are either of the hard or the soft type. Hard symptoms appear primarily in organic psychiatric disorders or as side effects of psychiatric therapy. They can also be encountered during neurological diseases of psychiatric patients. Their use in diagnostics and therapy is widely accepted. In contrast, soft neurological symptoms often stay unnoticed, even though they may contain important pieces of information. For this reason they will form the focus of our discussion. Soft neurological symptoms have been studied in different psychiatric disorder-groups. Up to now most attention has been devoted to schizophrenia. The study suggests that the soft symptoms are trait markers of schizophrenia. Furthermore they also signal disease activity and predict the outcome of the disease. Neurological symptoms are also important pointers for psychiatry. However, more systematic studies may increase the theoretical and practical implications of soft symptoms.

[Diabetes mellitus and Alzheimer's disease]. / Diabetes és Alzheimer-kór.

The incidence of Alzheimer's disease and diabetes is increasing with age. Thus, in light of demographic change and aging societies, they are becoming a growing issue for public health. Further, there are linkages between the two diseases. In particular, risk assessment studies suggest that type 2 diabetes mellitus is a risk factor of Alzheimer's disease. Hence, even though Alzheimer's disease can only be influenced to a limited extent, optimal treatment of diabetes mellitus may have also a positive effect on Alzheimer's disease. While the relationship between the two diseases is not yet completely clear, in addition to the known vascular effects of diabetes mellitus recent results shed light on central nervous system effects directly influencing the neurodegenerative process. Treatment of central insulin resistance, a phenomenon explored in recent years, may be a promising avenue, not only in addressing metabolic disorder, but also Alzheimer's disease.

Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia.

We tested the hypothesis whether the partially duplicated variant of alpha7 nicotinic acetylcholine receptor subunit gene (CHRFAM7A) 2-bp deletion (-2 bp) polymorphism and apolipoprotein E (ApoE) epsilon4 allele confer susceptibility to Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Pick's disease (PiD) and vascular dementia (VD). The study included 175 AD, 35 DLB patients, 38 PiD, 96 VD and 175 healthy control (HC) probands. The CHRFAM7A genotype without the -2 bp allele was significantly over-represented in AD (p = 0.011), DLB (p = 0.001) and PiD (p < 0.0001) compared to HC, but there were no statistical differences in VD (p = 0.407) compared to HC. We confirmed again that the ApoE epsilon4 allele is a risk factor for dementias. The -2 bp polymorphism of CHRFAM7A can be implicated in AD, DLB and PiD. However, it is unlikely that it plays an important role in the pathogenesis of VD.

Associative learning, acquired equivalence, and flexible generalization of knowledge in mild Alzheimer disease.

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.

Quantitative EEG in early Alzheimer's disease patients - power spectrum and complexity features.

The goal of this study was to investigate the EEG signs of early stage Alzheimer's disease (AD) by conventional analyses and by methods quantifying linear and nonlinear EEG-complexity. The EEG was recorded in 12 mild AD patients and in an age-matched healthy control group (24 subjects) in both eyes open and eyes closed conditions. Frequency spectra, Omega-complexity and Synchronization likelihood were calculated on the data. In the patients a significant decrease of the relative alpha and increase of the theta power were found. Remarkably increased Omega-complexity and lower Synchronization likelihood were observed in AD in the 0.5-25 Hz frequency ranges. It is concluded that both spectral- and EEG-complexity changes can be found already in the early stage of AD in a wide frequency range. Application of conventional EEG analysis methods in combination with quantification of EEG-complexity may improve the chances of early diagnosis of AD.

Decreased Event-Related Beta Synchronization During Memory Maintenance Marks Early Cognitive Decline in Mild Cognitive Impairment.

Mild cognitive impairment (MCI) refers to a measurable deficit in cognition in the absence of dementia or impairment in activities of daily living. Working memory impairment is among the earliest signs of MCI. Oscillatory analysis of working memory might be a potential tool for identifying patients at increased risk of developing dementia. Our study aimed to assess the temporospatial pattern of spectral differences during working memory maintenance between MCI patients and healthy controls and to compare the sources of oscillatory activity between the two groups. Event-related spectral perturbation of 17 MCI patients and 21 healthy control participants was studied with 128-channel EEG during the Sternberg working memory task. Source localization was performed by using the eLORETA software. Among the participants, 13 MCI and 15 control participants underwent a structural brain MRI examination. Event-related synchronization (ERS) in the alpha and beta frequency band was significantly lower in MCI patients compared to healthy control participants during retention. Both study groups showed significant memory load-related enhancement in both frequency band. In the MCI group, source localization revealed significantly attenuated beta oscillatory activity in the inferior and middle temporal gyrus, in the fusiform gyrus, and in the cuneus. Beta ERS correlated significantly with the size of the hippocampus, entorhinal cortex, and parahippocampal gyrus. During the retention period, MCI is characterized by decreased alpha and beta ERS compared to controls indicating early impairment in neural networks serving working memory maintenance. The assessment of electrophysiological changes in the beta frequency range may provide a useful diagnostic tool for the early detection of cognitive impairment.

What can DTI tell about early cognitive impairment? - Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging.

Mild cognitive impairment (MCI) gained a lot of interest recently, especially that the conversion rate to Alzheimer Disease (AD) in the amnestic subtype (aMCI) is higher than in the non-amnestic subtype (naMCI). We aimed to determine whether and how diffusion-weighted MRI (DWI) using the diffusion tensor model (DTI) can differentiate MCI subtypes from healthy subjects. High resolution 3D T1W and DWI images of patients (aMCI, n = 18; naMCI, n = 20; according to Petersen criteria) and controls (n = 27) were acquired at 3T and processed using ExploreDTI and SPM. Voxel-wise and region of interest (ROI) analyses of fractional anisotropy (FA) and mean diffusivity (MD) were performed with ANCOVA; MD was higher in aMCI compared to controls or naMCI in several grey and white matter (GM, WM) regions (especially in the temporal pole and the inferior temporal lobes), while FA was lower in WM ROI-s (e.g. left Cingulum). Moreover, significant correlations were identified between verbal fluency, visual and verbal memory performance and DTI metrics. Logistic regression showed that measuring FA of the crus of fornix along GM volumetry improves the discrimination of aMCI from naMCI. Additional information from DWI/DTI aids preclinical detection of AD and may help detecting early non-Alzheimer type dementia, too.

Changes of EEG spectra and coherence following performance in a cognitive task in Alzheimer's disease.

Electroencephalographic measures combined with cognitive tasks are widely used for the assessment of cognitive and pathophysiological changes in Alzheimer's disease (AD). Instead of the analysis of EEG data obtained during the performance of the task, in this study data recorded in the immediate after-task period were analyzed. It was expected that this period would correspond to the electrophysiological consequences of the cognitive effort. Data of 14 patients with AD (MMS score: 16-24) were compared to that of 10 healthy control subjects. Reverse counting of a fix duration was used as a cognitive task. Changes of relative frequency spectra, and those of inter-and intrahemispheric coherence were analyzed. Relative theta power was significantly higher in AD patients compared to the controls both before and after the task. The performance of the task resulted in an increase of the relative alpha2 band in the AD group, whereas it slightly decreased in the control group. The most prominent coherence differences between AD and controls were found in the alpha1 band, especially for long-range coherence values. Coherence in this frequency band increased in the control group following the task, not seen in the AD group. We conclude that EEG parameters calculated from epochs following the completion of a cognitive task clearly differentiates patients with AD from normal controls. The electrophysiological changes found in AD may correspond to the decrease of functional connectivity of cortical areas and to the malfunctioning of the networks engaged in the cognitive task investigated.

[Quantitative EEG analysis in Alzheimer's disease: spectral, coherence and complexity parameters]. / Kvantitatív EEG Alzheimer-kórban: spektrális-, koherencia- és komplexitás-jellemzok.

In our study we examined the linear and non-linear characteristics of EEG signals derived from patients with Alzheimer's disease (AD) with the future aim of developing a widely available method for monitoring therapy and the progression of the disease or to be used even for the purposes of differential diagnosis. EEG was recorded with eyes closed and eyes open conditions ("resting") in a group of patients with early-stage AD and in healthy control subjects matched by age. In addition to the conventional methods of analysis (frequency spectrum, coherence), the so-called complexity measures developed in recent years (Omega-complexity, synchronised probability) have also been determined. By means of frequency spectrum analysis, we managed to detect the slowdown of EEG in the early stage of dementia, a feature that so far has been associated with the later stages of AD. Coherence was reduced in the majority of frequency bands in the patient group; however, this difference could be observed only in some of the leads. Thus, resting EEG coherence is less suitable for separating various stages than the other methods. Complexity features have shown the most robust changes in Alzheimer's disease in our investigation. Besides the reduction in synchronised probability, significantly higher values of Omega-complexity were obtained in the patient group. This may be associated with the impairment of cortical afferentation (cholinergic and monoaminergic) and with the reduction in the number of neurons and synapses. Our methods have proved to be very sensitive to quantify these changes.

The Differentiation of Amnestic Type MCI from the Non-Amnestic Types by Structural MRI.

INTRODUCTION: While amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI) are theoretically different entities, only a few investigations studied the structural brain differences between these subtypes of mild cognitive impairment. The aim of the study was to find the structural differences between aMCI and naMCI, and to replicate previous findings on the differentiation between aMCI and healthy controls. METHODS: Altogether 62 aMCI, naMCI, and healthy control subjects were included into the study based on the Petersen criteria. All patients underwent a routine brain MR examination, and a detailed neuropsychological examination. RESULTS: The sizes of the hippocampus, the entorhinal cortex and the amygdala were decreased in aMCI relative to naMCI and to controls. Furthermore the cortical thickness of the entorhinal cortex, the fusiform gyrus, the precuneus and the isthmus of the cingulate gyrus were significantly decreased in aMCI relative to naMCI and healthy controls. The largest differences relative to controls were detected for the volume of the hippocampus (18% decrease vs. controls) and the cortical thickness (20% decrease vs. controls) of the entorhinal cortex: 1.6 and 1.4 in terms of Cohen's d. Only the volume of the precuneus were decreased in the naMCI group (5% decrease) compared to the control subjects: 0.9 in terms of Cohen's d. Significant between group differences were also found in the neuropsychological test results: a decreased anterograde, retrograde memory, and category fluency performance was detected in the aMCI group relative to controls and naMCI subjects. Subjects with naMCI showed decreased letter fluency relative to controls, while both MCI groups showed decreased executive functioning relative to controls as measured by the Trail Making test part B. Memory performance in the aMCI group and in the entire sample correlated with the thickness of the entorhinal cortex and with the volume of the amygdala. CONCLUSION: The amnestic mild cognitive impairment/non-amnestic mild cognitive impairment separation is not only theoretical but backed by structural imaging methods and neuropsychological tests. A better knowledge of the MCI subtypes can help to predict the direction of progression and create targeted prevention.

Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study.

BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline.

The nitric oxide synthase-3 codon 298 polymorphism is not associated with late-onset sporadic Alzheimer's dementia and Lewy body disease in a sample from Hungary.

An association study was performed between apolipoprotein E (apoE) polymorphism and the common structural polymorphism Glu/Asp at codon 298 of the nitric oxide synthase (NOS3) gene in late-onset sporadic Alzheimer's dementia probands (LOAD), diffuse Lewy body dementia cases (DLBD) and controls in a Hungarian sample. The frequency of individuals who carried the apoE epsilon4 allele was significantly more common in both dementia groups (LOAD, 20%; DLBD, 27%; control, 8%; control versus DLBD, chi2=13.264, degrees of freedom=2, P<0.001; control versus LOAD, chi2=6.628, degrees of freedom=2, P<0.036). However, there were no significant differences in the NOS3 genotype and allele distributions between the LOAD, DLBD and control groups. The apoE status has been found to be independent from the NOS3 codon 298 polymorphism in the examined cohort. Despite the facts that NOS3 is associated with neuritic sprouting, and aberrant neuronal and glial expression of the same molecule has been found in neurodegenerative diseases, it is unlikely that the polymorphism Glu/Asp of the NOS3 gene is involved in the development of LOAD and DLBD.