Body mass index and mild cognitive impairment-to-dementia progression in 24 months: a prospective study.

BACKGROUND/OBJECTIVES: Mild cognitive impairment (MCI), often considered as an early stage of dementia, is heterogeneous, and not all subjects with MCI progress into clinically diagnosed dementia. Low body weight (and body mass index, BMI) as well as losing weight while in MCI stadium have been proposed as possible risk factors of MCI-to-dementia conversion. SUBJECTS/METHODS: A prospective, 2-year observation of 102 MCI subjects has been conducted. Data on MCI subtype, somatic and neuropsychiatric co-morbidity and demographic characteristics (including age, gender and education), were collected. In addition, baseline and yearly BMI were calculated. RESULTS: Data of 83 out of the originally included 102 subjects were available after 2 years; 27 of those (32.5%) progressed to dementia. In univariate analysis, multiple-deficit MCI subtype (as compared with pure amnestic), higher age, the presence of diabetes and apathy, and lower baseline BMI (and losing weight on 2-year follow-up) were associated with conversion to dementia. Variables retained in the multivariate backward stepwise logistic regression model for conversion after 24 months of observation included lower baseline BMI (odds ratio, OR (95% cofidence interval, CI): 0.6 (0.4-0.9)), weight loss on 2-year follow-up (OR (95% CI): 1.3 (1.1-1.5)), male gender (OR (95% CI): 0.1 (0.01-0.9)) and presence of apathy (OR (95% CI): 70.7 (5.6-699)). Apathetic subjects had lower BMI and higher weight loss after controlling for potential confounders (age, gender, years of education and baseline ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) score). CONCLUSION: MCI subjects presenting with apathy, low initial BMI and losing weight on follow-up have a significantly greater risk of developing dementia. Nutritional and behavioural assessment should be considered as additional tools in evaluating the risk of dementia among MCI subjects.

Evaluation of the influence of metabolic processes and body composition on cognitive functions: Nutrition and Dementia Project (NutrDem Project).

The global increase in the prevalence of dementia and its associated comorbidities and consequences has stimulated intensive research focused on better understanding of the basic mechanisms and the possibilities to prevent and/or treat cognitive decline or dementia. The etiology of cognitive decline and dementia is very complex and is based upon the interplay of genetic and environmental factors. A growing body of epidemiological evidence has suggested that metabolic syndrome and its components may be important in the development of cognitive decline. Furthermore, an abnormal body mass index in middle age has been considered as a predictor for the development of dementia. The Nutrition and Dementia Project (NutrDem Project) was started at the Department of Old Age Psychiatry and Psychotic Disorders with close cooperation with Department of Medical Psychology. The aim of this study is to determine the effect of dietary patterns, nutritional status, body composition (with evaluation of visceral fat) and basic regulatory mechanisms of metabolism in elderly patients on cognitive functions and the risk of cognitive impairment (mild cognitive impairment and/or dementia).

Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus erythematosus--a case report.

Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric systemic lupus erythematosus (NPSLE), under some circumstances it appears to be difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or by other reasons such as primary mental disorders or substance-induced mood disorders, especially induced by glucocorticoids or antimalarials. We report the case of a male patient with SLE who presented with an exacerbation of bipolar disorder triggered by chloroquine. Firstly, when the patient was diagnosed with SLE, he underwent six months of therapy with chloroquine without any psychiatric symptoms. Later, the SLE returned and the patient was prescribed chloroquine again, without any mental illness. When the third exacerbation of SLE occurred, it coincided with a severe depressive episode with psychotic features that became aggravated for the first time after the administration of chloroquine. The chloroquine was subsequently replaced with hydroxychloroquine for the next six months without any behavioral problems, following which, the SLE and mood disorder were in remission. Later, a bipolar disorder relapse occurred, manifested by a manic episode, and in the following three months, despite psychiatric treatment, a manic episode with psychotic features developed four days after chloroquine was prescribed for arthritis. It was the second time that the mood disorder was exacerbated by chloroquine. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Our case points out that although chloroquine-induced psychosis is rare, patients presenting with behavioral changes need physicians' attention in order to diagnose early and efficiently treat encountered mood disorders.

Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population--a preliminary report.

OBJECTIVE: Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid ß deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. RESULTS: The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals (p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34-2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients (p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis (p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. CONCLUSION: In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.

CERAD Neuropsychological Total Scores Reflect Cortical Thinning in Prodromal Alzheimer's Disease.

BACKGROUND: Sensitive cognitive global scores are beneficial in screening and monitoring for prodromal Alzheimer's disease (AD). Early cortical changes provide a novel opportunity for validating established cognitive total scores against the biological disease markers. METHODS: We examined how two different total scores of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and the Mini-Mental State Examination (MMSE) are associated with cortical thickness (CTH) in mild cognitive impairment (MCI) and prodromal AD. Cognitive and magnetic resonance imaging (MRI) data of 22 progressive MCI, 78 stable MCI, and 98 control subjects, and MRI data of 103 AD patients of the prospective multicenter study were analyzed. RESULTS: CERAD total scores correlated with mean CTH more strongly (r = 0.34-0.38, p < 0.001) than did MMSE (r = 0.19, p = 0.01). Of those vertex clusters that showed thinning in progressive MCI, 60-75% related to the CERAD total scores and 3% to the MMSE. CONCLUSION: CERAD total scores are sensitive to the CTH signature of prodromal AD, which supports their biological validity in detecting early disease-related cognitive changes.

Consensus statement on dementia education and training in Europe.

OBJECTIVES: The aim of the current statement is to agree on: (1) what is the current situation with education and training on dementia in Europe; (2) what are the minimum educational requirements for professionals (neurologists, psychiatrists, primary care providers, nurses, biologists, neuroradiologists, etc.) regarding Alzheimer's disease and dementia, and (3) how to start a course of action for the future. DESIGN: In 2005, a simple questionnaire was sent to members of the European Alzheimer's Disease Consortium (EADC) concerning the education and training on dementia in their countries. Fourteen universities of the respective countries responded to this simple questionnaire. The answers varied, and the conclusion of this effort was that little was done concerning the training of students and health professionals on dementia. In 2008, another more structured and specified questionnaire was sent to professors in different universities of the same countries. RESULTS: The answers obtained were different from those of the previous questionnaire and demonstrated that it is very difficult to know about training and education in the field of dementia in every European country. CONCLUSION: From the data collected, it seems that although in the recent past little had been done concerning training on dementia, nowadays training has been developed in most European countries, and relevant educational projects exist both for medical students and doctors during their specialty training. Our main purpose is to develop training material or develop specific courses to improve the professional knowledge about dementia so that best medical and non-medical practice is implemented.

Ultrastructural study of florid plaques in variant Creutzfeldt-Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease.

BACKGROUND: Although the histological features of the amyloid plaques in variant Creutzfeldt-Jakob disease (vCJD) are distinct from those in other forms of prion disease [kuru, sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS)], their ultrastructural features have only been described in a single case report. AIMS: To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer disease (AD). METHODS: Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD. RESULTS: The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick 'tongues', in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron-dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane-bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques. CONCLUSIONS: The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.

Obstetric complications and Apgar score in early-onset schizophrenic patients with prominent positive and prominent negative symptoms.

UNLABELLED: The objective of the study was to find associations between obstetric complications (OCs) history and schizophrenia course and symptoms. We analysed the obstetric and psychiatric history of 50 DSM IV schizophrenic subjects who experienced their first schizophrenia episode in adolescence, and 30 healthy controls. Obstetrical data and Apgar scores were obtained from medical records and evaluated with the Lewis and Murray Scale. Based on patients' documentation [including longitudinal evaluation with Positive and Negative Syndrome Scale (PANSS)] the symptom profile and the course of schizophrenia were determined. RESULTS: we distinguished two major groups of patients: with prominent negative and prominent positive symptoms. Schizophrenics with prominent negative symptoms and a chronic schizophrenia course had significantly more definite OCs and lower Apgar scores than patients with prominent positive symptoms and controls. Subjects who had a positive OCs history were more than four times likely to develop schizophrenia in adolescence than those without such a history (OR=4.64; 95% CI=1.29-17.51) with the likelihood of developing schizophrenia with prominent negative symptoms especially high (OR=7.31; 95% CI=1.80-29.65). An Apgar score of between 0 and 3 after birth was associated with an increased risk for developing schizophrenia (OR=2.25; 95% CI=0.56-9.12), especially with prominent negative symptoms (OR=3.71; 95% CI=0.84-16.32). The findings support the hypothesis of a role of OCs in developing early-onset schizophrenia and suggest the associations of the OCs history with a specific symptoms profile (prominent negative symptoms) and a chronic course of schizophrenia.

["7 Minute Screening". Part I: a new tool in the diagnosis of Alzheimer's disease -- Polish translation and description of its clinical application]. / "7 minute screen" (7-minutowy test przesiewowy). Czesc I: Nowe narzedzie badawcze w chorobie Alzheimera--polskie tlumaczenie i opis zastosowania.

A polish translation and the description of the clinical use of the novel screening tool in Alzheimer's disease, a "7 Minute Screen", is presented.

["7 Minute Screening. Part II: the evaluation of the test sensitivity and specificity as compared to Mini-Mental State examination]. / "7 minute screen" (7-minutowy test przesiewowy). Czesc II: Ocena czulosci i swoistosci testu i porównanie z Mini Mental State.

In the paper an evaluation of basic accuracy parameters (sensitivity and specificity) of the polish version of "7 Minute Screen" as a screening tool for Alzheimer's disease is presented as well as its comparison to Mini Mental State.

[Risperidone in the ambulatory treatment of behavior disorders in demented patients of Alzheimer's type: a retrospective analysis]. / Risperidon w ambulatoryjnym leczeniu zaburzen zachowania u chorych z otepieniem typu Alzheimera: analiza retrospektywna.

Behavioural disturbances are common in the course of dementia in Alzheimer's disease (AD) and their treatment is usually difficult. Different pharmacological and non-pharmacological options are employed basing mainly on clinical experience, still the number of well-designed, controlled studies in the field is very small. Novel, atypical neuroleptics, including risperidone might potentially be one of these options, taking into account their good safety profile and clinical efficacy in closely related syndromes. We present the results of a retrospective analysis of 57 outpatients with behavioural symptoms complicating AD treated with risperidone, either alone or in combination with one of the acetylcholinesterase inhibitor (AchEI; donepezil or rivastigmine). Seventy five percent of patients treated responded to risperidone with the usual effective dose of 0.5-1 mg/day. The influence of risperidone treatment on behavioural symptomatology was irrespective to the use of AchEI and equally well safe in both groups. The clinical response to the treatment was seen usually within first 2-3 weeks, those who did not respond early tended not to respond later on as well. Additionally, if not responding to low doses of risperidone (0.5-1 mg/day), patients usually did not respond to higher doses or could not tolerate them, mainly due to emerging extrapyramidal symptoms (EPS). Low doses of risperidone were well tolerated, with the fraction of patients experiencing EPS not achieving 10%. EPS observed, were dose dependent and tended to appear if the dose acceleration was fast. We then recommend low doses of risperidone and its slow titration if needed.

The morphometric analysis and recognition an amyloid plaque in microscope images by computer image processing.

This paper presents an approach of the two-dimensional image processing application in recognition of amyloid plaque in microscope images of the brain tissues. The authors propose to create universal amyloid plaque computer pattern and special multivariate image segmentation techniques based on collected images and statistical information. This recognition image procedure is divided into 3-dimensional statistical colour and morphological shape identifications. The developed computer system will collect and store image data and exchange them by network with other collaborated systems.

[The costs of Alzheimer's disease treatment: the rationale of acetylcholinesterase inhibitors use?]. / Koszty leczenia w chorobie Alzheimera--czy stosowanie inhibitorów acetylocholinesterazy jest ekonomicznie uzasadnione?

The costs of Alzheimer's disease treatment in the era of acetylcholinesterase inhibitors use are critically discussed.

[Modern views on etiopathogenesis of Alzheimer's disease]. / Wspólczesne poglady na etiopatogeneze choroby Alzheimera.

The aetiology of Alzheimer's disease (AD) remains, despite vast progress, not fully understood. Four genes involved in the development of the disease have been identified. Three fully penetrant ones (the amyloid beta-protein precursor on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1) lead to the development of relatively rare familial form of AD. Together, they account for about half of this early-onset form of the disease. One genetic risk factor--polipoprotein E-4--is associated with late-onset Alzheimer's disease while at least two others are proposed. None of these genes can be by now adopted for use as a diagnostic or predictive test for Alzheimer's disease. Apart from the above, some environmental factors are also implicated in pathogenesis of the disease with the amyloid cascade hypothesis being the most commonly accepted as central. In the presented paper we have critically reviewed a literature on etiopatogenesis of Alzheimer's disease and discussed some practical consequences of the progress in understanding the mechanism of the disease.

Distribution of apolipoprotein E4 isoform in Alzheimer's disease in Poland.

Alzheimer's disease (AD) is the most common human progressive dementia linked, in its sporadic form, to a common polymorphism within a gene for apolipoprotein E (APOE) mapped to chromosome 19. Individuals with APOE 4 isoforms are more prone to develop sporadic from of AD than those who carry APOE 2 or APOE 3 alleles. As distribution of APOE isoforms in Poland is unknown, we decided to study it in AD and control cases. In AD group, three patients (23.1%) were homozygous for APOE 4, four cases (30.8%) were heterozygous and six cases (46%) carried no APOE 4 allele. In control group (n-11), only one case (9.1%) was homozygous for APOE 4 allele, no case was heterozygous for APOE 4 while 10 cases (90.9%) carried no APOE 4 alleles. Our results are virtually identical to those reported from Western countries.

Programmed cell death (apoptosis) in Alzheimer's disease and Creutzfeldt-Jakob disease.

The aim of our study was the estimation of the apoptosis process using in situ-end labelling of DNA breaks method on paraffin sections in 5 human cases of Alzheimer's disease (AD), 6 of Creutzfeldt-Jakob disease (CJD) and in 25 mice infected experimentally with the Fujisaki strain of CJD, killed sequentially at one-week intervals. The numbers of apoptotic cells in CJD-infected mice in the later stages of the disease and in terminally ill mice were progressively higher that at the early stage of the disease. Further, we found a correlation between the intensity of apoptosis and major lesions hallmark of disease--the intensity of spongiform changes in the cerebral cortex but not in the accumulation of PrP in CJD infected mice. The number of A beta-amyloid plaques in AD was not related to apoptotic index. Our study showed that apoptosis is a very important event in these neurodegenerative diseases and may become a basic mechanism in loss of neurons.

An ultrastructural and molecular perspective of the pathological hallmarks of Alzheimer's disease.

An update review of selected issues of the current knowledge of the pathology of Alzheimer's disease, by far the most common cause of human dementia is presented. The molecular basis of the most prominent ultrastructural features of AD including neurofibrillary tangles and the amyloid plaque as well as dystrophic neurites and neuropil threads. The major role of betaAPP and its metabolic pathways in the pathogenesis of AD has been strongly pointed out.

[Amyloid plaque in selected neurodegenerative disorders of the central nervous system]. / Plytka amyloidowa w niektórych chorobach zwyrodnieniowych osrodkowego ukladu nerwowego.

In this paper a review of the most recent investigations of the pathology of amyloid and of amyloid plaque is presented. The purpose of this report is to describe various clinical conditions (including their etiopathology and clinical manifestations) in which amyloid deposits (especially amyloid plaques) are significant features of the disease. Similarly, to define the neuropathological picture of amyloid deposits, molecular composition of amyloid fibrils and the genes which encode them.