Cognitive impairment after tick-borne encephalitis.

BACKGROUND/AIMS: Tick-borne encephalitis (TBE) is a potentially debilitating disease caused by the TBE virus. Natural foci of TBE were localized in the Lublin region (Poland). We observed the growing tendency of the incidence of TBE in the Lublin region at the beginning of the 1990s. Farmers and forestry workers were most often infected due to the occupational risk. METHODS: Forty farmers with TBE since the beginning of the year 2001 were included in the study. Serological measurements as well as medical and neuropsychological examination confirmed the infection. Dementia and mild cognitive impairment were diagnosed on the basis of DSM-IV-R, ICD-10 and Petersen criteria, respectively. RESULTS: Long-term consequences of the illness have been reported in 22 subjects. In this group, cognitive impairment of the amnestic type was diagnosed. No decline in cognitive status was observed in the examined patients for 6 months. CONCLUSIONS: The diagnosis of human TBE is usually based on serology, which has a number of pitfalls. The outcome of the disease can mimic many neurological diseases. For that reason, the history of farmers with cognitive decline should be carefully examined. There is reasonable likelihood of cognitive decline in patients with TBE.

Homocysteine, antioxidant vitamins and lipids as biomarkers of neurodegeneration in Alzheimer's disease versus non-Alzheimer's dementia.

INTRODUCTION AND OBJECTIVE: Evidence for the benefit of antioxidants' based therapeutic intervention in dementia are inconsistent. Parallel studies in disease forms of dementia different than Alzheimer's are even less conclusive. In this study, the role of serum levels of homocysteine (tHcy), lipids and antioxidants in predicting the risk of cognitive decline in Alzheimer's disease (AD) versus non-Alzheimer's dementias (n-AD). The objective was to add to the ongoing cumulative research to establish the biochemical baseline for potential nutri-therapeutic intervention in different forms of dementia. MATERIALS AND METHOD: 65 participants with dementia (DP-s) were divided into two groups: ADP--patients with Alzheimer's disease and n-ADP--patients with dementia of a different etiology than primary neurodegenerative dementia in the course of Alzheimer's disease. Cognitive function was assessed by Mini-Mental State Examination (MMSE) and related to plasma levels of tHcy, folate, vitamins B-6, B-12, lipids and vitamins A and E for both groups. Also examined were associations between cognitive impairment and several variables (age, education, duration of dementia) that might confound nutrition-cognition associations. RESULTS: A significant reduction in serum vitamin A levels and elevation of total cholesterol levels were shown for the DP-s group compared to those in the control group. Moreover, significant differences were found in MMSE data and serum vitamin E and tHcy levels between patients with ADP and n-ADP. The scores for MMSE showed a correlation with the vitamin E levels and duration of dementia in the ADP group and/or correlation with tHcy, levels of vitamins A and/or E, and duration of dementia in the n-ADP group. CONCLUSIONS: The results obtained suggest that elevated serum tHcy and decreased levels of vitamins A and E are associated with an increased risk of non-Alzheimer's dementias, although further studies involving a larger cohort are now needed to verify these results.

Lipids' peroxidation markers in Alzheimer's disease and vascular dementia.

AIM: Although a large body of evidence supports a role of oxidative stress in the etiopathogenesis of dementia, there is still a substantial lack of data regarding the biomarkers of oxidative stress characteristic of Alzheimer's disease (AD) as opposed to different types of dementia. In this study, the level of various oxidative stress parameters were measured in AD, vascular dementia (VaD), and age- and sex-matched control patients. The AD and VaD patients all had similar levels of cognitive impairment as measured by the Mini-Mental State Examination. METHODS: Thirty AD, 19 VaD and 29 controls patients were recruited to the study. Plasma levels of malondialdehyde (MDA), total sulfhydryl (T-SH), calcium (Ca(++)) and magnesium (Mg(++)) were measured. RESULTS: In both AD and VaD groups, the levels of oxidative stress parameters were higher compared with controls. Further, the VaD patients expressed significantly higher levels of plasma parameters of oxidative stress than AD. The difference was noted in MDA, the marker of lipid peroxidation, whereas in VaD the level of MDA was more than 2.8-fold higher than that registered in AD patients. CONCLUSION: Vascular dementia in patients is characteristic of increased levels of oxidative stress, especially lipid peroxidation markers. This finding is relevant to determining the pathophysiology of dementia, particularly in the light of the recently suggested importance of the vascular component in dementia development, in addition to aiding in the diagnosis of VaD following clinical presentation. The study will be continued to compare the character and level of decline in both groups.

Dissociated amyloid-beta antibody levels as a serum biomarker for the progression of Alzheimer's disease: a population-based study.

With an ever growing population of aged individuals who are at risk of developing Alzheimer disease (AD), there is an urgent need for a sensitive, specific, and preferably non-invasive diagnostic standard of disease progression. Mainstream thinking suggests that early intervention is key to maximizing the opportunity for a successful treatment regimen in AD and, as such, an early and accurate means of diagnosis is essential. In this study, we applied a recently described antibody-antigen dissociation technique to samples obtained as part of a population-based analysis of the prevalence of AD. Stratified sampling and random selection strategies were combined to obtain a representative population for screening of individuals older than 55 years. Serum antibodies to amyloid-beta (Abeta)(1-42) were measured before and after antigen dissociation. The difference between the two measurements was indicated as the dissociation delta (Delta). Our analyses showed that the levels of dissociated antibody in AD patients were always significantly different from controls and that levels of Abeta antibody after dissociation, but not those of non-dissociated antibody, correlated negatively (p<0.05) with both duration of the disease and age in the AD patients. Moreover, the change in concentration of Abeta antibody from pre- to post-dissociation (i.e., the dissociation Delta) directly reflected the progression of AD in terms of both time since diagnosis and age of the patients, with a lower dissociation Delta indicating a more advanced stage of AD. Ultimately, these data suggest that dissociated Abeta antibody levels are of significant diagnostic value at the onset of the neurodegenerative process and, thereafter, may be a useful biomarker for disease progression.

Biomarkers in Alzheimer's disease: past, present and future.

Epidemiological and molecular studies suggest that Alzheimer's disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-beta and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial. The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD. In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-beta, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.

Dietary patterns associated with Alzheimer's disease: population based study.

Recently dietary pattern analysis has emerged as a way for examining diet-disease relations in Alzheimer's disease. In contrast with the conventional approach, which focuses on a single nutrient or a few nutrients or foods, this method considers overall eating patterns. We examined the dietary patterns defined by factor analysis using data collected with a food-frequency questionnaire in people with Alzheimer's disease (AD) as compared to healthy controls. The diet data were obtained during population based study of the prevalence of Alzheimer's disease in a population in Poland. Stratified sampling and random selection strategies were combined to obtain a representative population for screening (age group > 55). From the population screened three times, 71 people were diagnosed with Alzheimer's according to DSM-IV, and were recruited for further diet risk factors assessment. A group of people with Alzheimer disease (n = 71; F/M 42/29) and the same number of healthy, age and gender matched control were recruited for the study. Patients and their caregivers as well as controls were presented with a food frequency questionnaire based on the 12 food groups. Factor analysis (principal component) was used to derive food patterns. The analysis was conducted using the factor procedure. The factors were rotated by an orthogonal transformation (Varimax rotation) to achieve simpler structure with greater interpretability. Using factor analysis, we identified major eating patterns, one for Alzheimer's patients and a different one for control group. The AD dietary pattern, FACTOR AD was characterized by a high intake of meat, butter, high-fat dairy products, eggs, and refined sugar, whereas the other pattern, (FACTOR C) was characterized by a high intake of grains and vegetables. These data indicate the existence of dietary patterns defined by factor analysis with data from a food frequency questionnaire, characteristic for Alzheimer's disease in a Polish population.

Mitochondrial Drugs for Alzheimer Disease.

Therapeutic strategies for Alzheimer disease (AD) have yet to offer a disease-modifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.

All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease.

Retinoic acid, an essential factor derived from vitamin A, has been shown to have a variety of functions including roles as an antioxidant and in cellular differentiation. Since oxidative stress and dedifferentiation of neurons appear to be common pathological elements of a number of neurodegenerative disorders, we speculated that retinoic acid may offer therapeutic promise. In this vein, recent compelling evidence indicates a role of retinoic acid in cognitive activities and anti-amyloidogenic properties. Here, we review the actions of retinoic acid that indicate that it may have therapeutic properties ideally served for the treatment of neurodegenerative diseases such as Alzheimer's disease.