The impact of sleep education, light intervention and relaxation on sleep and mood in the elderly.

Sleep and light education (SLE) combined with relaxation is a potential method of addressing sleep and affective problems in older people. 47 participants took part in a four-week sleep education program. SLE was conducted once a week for 60-90 minutes. Participants were instructed on sleep and light hygiene, sleep processes, and practiced relaxation techniques. Participants were wearing actigraphs for 6 weeks, completed daily sleep diaries, and wore blue light-blocking glasses 120 minutes before bedtime. Measures included scores of the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI) and actigraphy measurements of sleep latency, sleep efficiency, and sleep fragmentation. Sleep quality increased after SLE based on the subjective assessment and in the objective measurement with actigraphy. PSQI scores were statistically reduced indicating better sleep. Scores after the intervention significantly decreased in ESS and ISS. Sleep latency significantly decreased, whereas sleep efficiency and fragmentation index (%), did not improve. Mood significantly improved after SLE, with lower scores on the BDI-II and STAI. SLE combined with relaxation proved to be an effective method to reduce sleep problems and the incidence of depressive and anxiety symptoms.

Impaired intestinal permeability in patients with multiple sclerosis.

BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

Effects of human probiotics on memory and psychological and physical measures in community-dwelling older adults with normal and mildly impaired cognition: results of a bi-center, double-blind, randomized, and placebo-controlled clinical trial (CleverAge biota).

Objectives: This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at clinicaltrials.gov NCT05051501 and described in detail in our previous paper. Methods: Community dwelling participants aged between 55 and 80 years were randomly assigned to receive a single dose of 106 colony-forming units of human Streptococcus thermophilus GH, Streptococcus salivarius GH NEXARS, Lactobacilus plantarum GH, and Pediococcus pentosaceus GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3 months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6 months a small number of volunteers were additionally assessed after 2 months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance. Results: At baseline, the probiotic-placebo group A (n = 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (n = 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8 months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3 months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months. Conclusion: The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions. Clinical trial registration: clinicaltrials.gov, identifier NCT05051501.

Basal Ganglia Compensatory White Matter Changes on DTI in Alzheimer's Disease.

The volume reduction of the gray matter structures in patients with Alzheimer's disease is often accompanied by an asymmetric increase in the number of white matter fibers located close to these structures. The present study aims to investigate the white matter structure changes in the motor basal ganglia in Alzheimer's disease patients compared to healthy controls using diffusion tensor imaging. The amounts of tracts, tract length, tract volume, quantitative anisotropy, and general fractional anisotropy were measured in ten patients with Alzheimer's disease and ten healthy controls. A significant decrease in the number of tracts and general fractional anisotropy was found in patients with Alzheimer's disease compared to controls in the right caudate nucleus, while an increase was found in the left and the right putamen. Further, a significant decrease in the structural volume of the left and the right putamen was observed. An increase in the white matter diffusion tensor imaging parameters in patients with Alzheimer's disease was observed only in the putamen bilaterally. The right caudate showed a decrease in both the diffusion tensor imaging parameters and the volume in Alzheimer's disease patients. The right pallidum showed an increase in the diffusion tensor imaging parameters but a decrease in volume in Alzheimer's disease patients.

Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota).

Background: Gut microbiota may influence brain functions. Therefore, we prepared a study protocol for a double-blind, crossover, randomized clinical trial to determine the complex effects of human probiotics on memory, psychological, and biological measures in the elderly. Methods: We selected eligible participants using an effective electronic questionnaire containing the inclusion and exclusion criteria and a brief electronic cognitive test. One-third of the respondents with the worst cognitive scores on the electronic test are randomized to group A, starting with a 3-month probiotic intervention, and to group B, starting with a placebo. In a crossover design, both groups change their intervention/placebo status after 3 months for the next 3 months. Participants refusing longer personal assessments due to the COVID-19 pandemic were randomly allocated to one of two subgroups assessed online. Participants in both groups are matched in age, education, gender, and cognitive scores on electronic testing at baseline. At three time points, participants are assessed using a neuropsychological battery, self-report measures of mood, a physical fitness test, blood, urine, and stool samples, and actigraphy. A subset of participants also provided their biological samples and underwent the neuropsychological battery in an extended testing phase 3 months after study termination to find out the long-term effect of the intervention. Discussion: This is the first trial to address the comprehensive effects of human probiotics on memory and many other measures in the elderly. We assume that the probiotic group will have better outcomes than the placebo group after the first and second trimesters. We expect that the probiotic effect will persist for the next 3 months. These study's findings will contribute to an interesting area of how to improve memory, psychological and biological and other factors naturally and will examine the importance of probiotics for overall health in the elderly. Clinical trial registration: [clinicaltrials.gov], identifier [NCT05051501].

COMIRESTROKE-A clinical study protocol for monitoring clinical effect and molecular biological readouts of COMprehensive Intensive REhabilitation program after STROKE: A four-arm parallel-group randomized double blinded controlled trial with a longitudinal design.

Introduction: While the role of physiotherapy as part of a comprehensive inpatient rehabilitation is indisputable, clear evidence concerning the effectiveness of different rehabilitation managements [interdisciplinary implementing the International Classification of Functioning, disability and health (ICF) vs. multidisciplinary model] and physiotherapy categories (neuroproprioceptive "facilitation, inhibition" vs. motor/skill acquisitions using technologies) are still lacking. In this study, four kinds of comprehensive inpatient rehabilitation with different management and content of physical therapy will be compared. Moreover, focus will be placed on the identification of novel biological molecules reflective of effective rehabilitation. Long non-coding RNAs (lncRNAs) are transcripts (>200 bps) of limited coding potential, which have recently been recognized as key factors in neuronal signaling pathways in ischemic stroke and as such, may provide a valuable readout of patient recovery and neuroprotection during therapeutic progression. Methods and analysis: Adults after the first ischemic stroke in an early sub-acute phase with motor disability will be randomly assigned to one of four groups and undergo a 3 weeks comprehensive inpatient rehabilitation of different types: interdisciplinary team work using ICF model as a guide; multidisciplinary teamwork implementing neuroproprioceptive "facilitation and inhibition" physiotherapy; multidisciplinary teamwork implementing technology-based physiotherapy; and standard multidisciplinary teamwork. Primary (the Goal Attainment Scale, the Patient-Reported Outcomes Measurement Information System, and the World Health Organization Disability Assessment Schedule) and secondary (motor, cognitive, psychological, speech and swallowing functions, functional independence) outcomes will be measured. A blood sample will be obtained upon consent (20 mls; representing pre-rehabilitation molecular) before and after the inpatient program. Primary outcomes will be followed up again 3 and 12 months after the end of the program. The overarching aim of this study is to determine the effectiveness of various rehabilitation managements and physiotherapeutic categories implemented by patients post ischemic stroke via analysis of primary, secondary and long non-coding RNA readouts. This clinical trial will offer an innovative approach not previously tested and will provide new complex analysis along with public assessable molecular biological evidence of various rehabilitation methodology for the alleviation of the effects of ischemic stroke. Clinical trial registration: NCT05323916, https://clinicaltrials.gov/ct2/show/NCT05323916.

High electronic name agreement of 70 pictures in normative study of 5,290 Czechs for easy multicultural replication.

The aim of this normative study was to verify recognition and name agreement of 70 black and white line pictures on a large Czech population sample using an electronic form. The set of pictures was selected based on previous research showing preliminary evidence of high name agreement with one word only. The pictures were arrayed into an electronic form that was distributed via the internet and filled in by 6,055 participants across the whole country. The group for final evaluation comprised of 5,290 respondents (age range 11-90 years, average ± SD: 53 ± 15 years, 77% of women, years of completed education: range 8-28 years, 15 ± 3 years) from all regions. The average name agreement for all pictures was 98%. Name agreement in the majority of pictures was not influenced by gender, age, and education. The most useful 14 pictures are entirely independent of all sociodemographic factors and include table, scissors, bell, ski, crown, chimney, glasses, steering wheel, heart, chain, ladder, horseshoe, bone, and alarm clock. The presented set of pictures named by one word only can be used for diagnostic or therapeutic purposes. The pictures and the electronic form are freely available for replication in other languages at our website www.abadeco.cz.

Hippocampo-Horn Percentage and Parietal Atrophy Score for Easy Visual Assessment of Brain Atrophy on Magnetic Resonance Imaging in Early- and Late-Onset Alzheimer's Disease.

BACKGROUND: Magnetic resonance imaging (MRI) visual scales of brain atrophy are important for differential diagnosis of dementias in routine clinical practice. Atrophy patterns in early- and late-onset Alzheimer's disease (AD) can be different according to some studies. OBJECTIVE: Our goal was to assess brain atrophy patterns in early- and late-onset AD using our recently developed simple MRI visual scales and evaluate their reliability. METHODS: We used Hippocampo-horn percentage (Hip-hop) and Parietal Atrophy Score (PAS) to compare mediotemporal and parietal atrophy on brain MRI among 4 groups: 26 patients with early-onset AD, 21 younger cognitively normal persons, 32 patients with late-onset AD, and 36 older cognitively normal persons. Two raters scored all brain MRI to assess reliability of the Hip-hop and PAS. Brain MRIs were obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. RESULTS: The patients with early-onset AD had significantly more pronounced mediotemporal and also parietal atrophy bilaterally compared to the controls (both p < 0.01). The patients with late-onset AD had significantly more pronounced only mediotemporal atrophy bilaterally compared to the controls (p < 0.000001), but parietal lobes were the same. Intra-rater and inter-rater reliability of both visual scales Hip-hop and PAS were almost perfect in all cases (weighted-kappa value ranged from 0.90 to 0.99). CONCLUSION: While mediotemporal atrophy detected using Hip-hop is universal across the whole AD age spectrum, parietal atrophy detected using PAS is worth rating only in early-onset AD. Hip-hop and PAS are very reliable MRI visual scales.

Reliability and Validity of the Czech Version of the Pittsburgh Sleep Quality Index in Patients with Sleep Disorders and Healthy Controls.

OBJECTIVES: Psychometric properties of the Czech version of the Pittsburgh Sleep Quality Index (PSQI-CZ) have been evaluated only in patients with chronic insomnia, and thus, it is unclear whether PSQI-CZ is suitable for use in other clinical and nonclinical populations. This study was aimed at examining the validity and reliability of the PSQI-CZ and at assessing whether the unidimensional or multidimensional scoring of the instrument would be recommended. METHODS: A total of 524 adult subjects from the Czech population participated in the study. The internal consistency of PSQI was evaluated using Cronbach's alpha. The known-group validity was tested using the Kruskal-Wallis H test to verify the difference between patients with sleep disorders and healthy control sample. For testing the structural validity, a cross-validation approach was used with both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). For EFA, the maximum likelihood method with direct oblimin rotation and parallel analysis was used. RESULTS: The internal consistency of PSQI-CZ items was moderate (α = 0.75). Receiver operating characteristic (ROC) curve analysis showed high specificity (0.79) and moderate sensitivity (0.64) using an optimal cut-off score of 10. The EFA revealed a 3-factor structure with factors labelled as "sleep duration and efficiency," "sleep disturbances and quality," and "sleep latency." The CFA showed that the emerged 3-factor model had a partly acceptable fit, which was better than other previously supported models. CONCLUSIONS: A high cut-off score of 10 is recommended to define poor sleep quality. Given the inconsistency of structural analyses, alternative scoring was not recommended. However, the individual components in addition to a total score should be interpreted when assessing sleep quality. We recommend editing and verifying the PSQI-CZ translation.

Neuronal and glial CSF biomarkers in multiple sclerosis: a systematic review and meta-analysis.

Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.

The Parietal Atrophy Score on Brain Magnetic Resonance Imaging is a Reliable Visual Scale.

AIMS: The purpose of the study was to evaluate the reliability of our new visual scale for a quick atrophy assessment of parietal lobes on brain Magnetic Resonance Imaging (MRI) among different professionals. A good agreement would justify its use for differential diagnosis of neurodegenerative dementias, especially early-onset Alzheimer's Disease (AD), in clinical settings. METHODS: The visual scale named the Parietal Atrophy Score (PAS) is based on a semi-quantitative assessment ranging from 0 (no atrophy) to 2 (prominent atrophy) in three parietal structures (sulcus cingularis posterior, precuneus, parietal gyri) on T1-weighted MRI coronal slices through the whole parietal lobes. We used kappa statistics to evaluate intra-rater and inter-rater agreement among four raters who independently scored parietal atrophy using PAS. Rater 1 was a neuroanatomist (JM), rater 2 was an expert in MRI acquisition and analysis (II), rater 3 was a medical student (OP) and rater 4 was a neurologist (DS) who evaluated parietal atrophy twice in a 3-month interval to assess intra-rater agreement. All raters evaluated the same 50 parietal lobes on brain MRI of 25 cognitively normal individuals with even distribution across all atrophy degrees from none to prominent according to the neurologist's rating. RESULTS: Intra-rater agreement was almost perfect with the kappa value of 0.90. Inter-rater agreement was moderate to substantial with kappa values ranging from 0.43-0.86. CONCLUSION: The Parietal Atrophy Score is the reliable visual scale among raters of different professions for a quick evaluation of parietal lobes on brain MRI within 1-2 minutes. We believe it could be used as an adjunct measure in differential diagnosis of dementias, especially early-onset AD.

Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

IMPORTANCE: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. OBJECTIVES: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. DATA SOURCES: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. STUDY SELECTION: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. DATA EXTRACTION AND SYNTHESIS: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. MAIN OUTCOME AND MEASURE: The cNfL levels adjusted for age and sex across diagnoses. RESULTS: Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. CONCLUSIONS AND RELEVANCE: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

Brain volumes and their ratios in Alzheimer´s disease on magnetic resonance imaging segmented using Freesurfer 6.0.

Ratios between opposing volumes from brain magnetic resonance imaging (MRI) can provide additional information to volumes in Alzheimer's disease (AD). Brain three-dimensional MPRAGE MRI at 3T were segmented into 44 regions using FreeSurfer v6 in 75 participants. The region's size in absolute volumes and relative proportions to the whole brain volume were compared between 39 AD patients and 36 age-, education- and sex-matched normal controls (NC). Volumes of the most atrophied parts were related to the opposing volumes of the most enlarged parts as ratios. The most atrophic structures in AD were both hippocampi. By contrast, the greatest enlargements in AD were inferior parts of both lateral ventricles. The best ratio for each side was the hippocampo-horn proportion calculated as ratio: the hippocampus / (the hippocampus + inferior lateral ventricle). Its optimal cut-off of 74% yielded sensitivity of 74% and specificity of 78% on the left and sensitivity of 74% and specificity of 78% on the right. The hippocampo-horn proportion is another measure to evaluate the degree of hippocampal atrophy on brain MRI in percentages. It has a potential to be simplified into a comparison of two-dimensional corresponding areas or a visual assessment.

Pyramidal system involvement in progressive supranuclear palsy - a clinicopathological correlation.

BACKGROUND: We aimed to produce a detailed neuropathological analysis of pyramidal motor system pathology and provide its clinical pathological correlation in cases with definite progressive supranuclear palsy (PSP). METHODS: Pyramidal motor system pathologies were analyzed in 18 cases with neuropathologically confirmed PSP. Based on a retrospective clinical analysis, cases were subtyped according to Movement Disorder Society criteria for clinical diagnosis of PSP as probable, possible or suggestive of PSP with Richardson's syndrome (n = 10), PSP with predominant corticobasal syndrome (n = 3), PSP with predominant parkinsonism (n = 3), PSP with predominant speech/language disorder (n = 1), and PSP with progressive gait freezing (n = 1). Clinical manifestations of motor neuron involvement (pseudobulbar or bulbar signs and spasticity) were retrospectively assessed semiquantitatively. Neuropathologically, hyperphosphorylated tau-related pyramidal motor system neuronal, neuritic, and glial pathology using anti-tau AT8 clone immunohistochemistry, was also evaluated. RESULTS: Clinical manifestations of pyramidal motor system involvement were found in patients with different PSP subtypes. A statistically significant higher load of tau pathology was found in the pyramidal system in PSP-Richardson's syndrome compared to other PSP subtypes (p = 0.016); however, there was no significant correlation between pyramidal system tau pathology and related motor clinical symptoms. CONCLUSIONS: Tau pathology in the spinal cord and pyramidal motor system structures is very common in progressive supranuclear palsy and may neuropathologically supplement the distinction between classic Richardson's syndrome from other progressive supranuclear palsy subtypes.

Surface tension and intrinsic amyloid fluorescence of serum and cerebrospinal fluid samples in Alzheimer´s disease.

AIM: Surface tension of biological fluids can be influenced by changes in oligomerization or aggregation of surfactant peptides or proteins. Amphiphilic peptides of amyloid-ß or other amyloidogenic peptides/proteins display properties of surfactants, oligomerization and aggregation increase also their fluorescence intensity compared with native structures. Results/methodology: We estimated surface tension and native/ThioflavinT-based/intrinsic amyloid fluorescence intensity in serum and cerebrospinal fluid samples for their evalution as diagnostic biomarkers for Alzheimer´s disease (AD). DISCUSSION/CONCLUSION: Our results indicate that values of surface tension are not a suitable biomarker for AD. However, the ratio of ThioflavinT-based fluorescence to intrinsic amyloid fluorescence in cerebrospinal fluid appears to be an acceptable supportive diagnostic biomarker for AD (its sensitivity was 61.1%, and the specificity 70.8% when compared with aged controls).

Levels of 17ß-hydroxysteroid dehydrogenase type 10 in CSF are not a valuable biomarker for multiple sclerosis.

AIM: We aimed to characterize the role of mitochondrial 17ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD10) overexpression in multiple sclerosis (MS) and to evaluate its use as a biomarker. Materials & methods: We estimated levels of 17ß-HSD10, amyloid ß 1-42, cyclophilin D, 17ß-HSD10-cyclophilin D complexes or 17ß-HSD10-parkin complexes in cerebrospinal fluid (CSF) samples. RESULTS: The increase in 17ß-HSD10 levels or in 17ß-HSD10-parkin complexes and links to leukocytes were found only in relapsing-remitting MS. The sensitivity of the biomarker was 64%, the specificity equaled 60-63% compared with controls. CONCLUSION: Increased CSF levels of 17ß-HSD10 in later stages of MS could be interpreted via its upregulation in demyelinated neuronal axons. CSF levels of 17ß-HSD10 are not the valuable biomarker for the early diagnosis or for the progression of MS.

Validation of the Czech Montreal Cognitive Assessment for Mild Cognitive Impairment due to Alzheimer Disease and Czech Norms in 1,552 Elderly Persons.

BACKGROUND: The Czech version of the Montreal Cognitive Assessment (MoCA-CZ) and delayed recall of 5 words have not been validated in patients with mild cognitive impairment (MCI) due to Alzheimer disease (AD) and compared to norms of a large population. METHOD: The MoCA-CZ was administered to 1,600 elderly individuals in 2 groups consisting of 48 patients with MCI due to AD (AD-MCI) and 1,552 normal elderly adults. RESULTS: MoCA-CZ scores were significantly lower in the AD-MCI patients than in the normal elderly (21 ± 4 vs. 26 ± 3 points; p = 0.03). Under the recommended cutoff score of ≤25, the MoCA-CZ demonstrated an excellent sensitivity of 94% but a low specificity of 62%. When the score was reduced to ≤24, the MoCA-CZ showed an optimal sensitivity of 87% for AD-MCI and a specificity of 72%. Normal elderly persons should recall at least 2 words after delay (sensitivity 80%, specificity 74%). Several cutoff points were derived from normative data stratified by age and education. CONCLUSIONS: The cutoff for AD-MCI and stratified norms are available for the MoCA total score and delayed recall of the Czech version. The cut-off scores of the MoCA-CZ, sensitivity, and specificity are lower than in the original study.

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder.

OBJECTIVE: To evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies. METHODS: We assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls. RESULTS: The RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h. CONCLUSIONS: Our results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.

Lower Serum Antibodies Against Tau Protein and Heavy Neurofilament in Alzheimer's Disease.

BACKGROUND: Unlike antibodies against amyloid-ß, little is known about serum antibodies to neuron-specific cytoskeletal proteins in patients with Alzheimer's disease (AD). OBJECTIVE: We aimed to study IgG autoantibodies against tau protein, light (NFL) and heavy subunits (NFH) of neurofilaments in serum of AD patients and elderly controls and to explore the evolution of antineurocytoskeletal antibody levels over time. METHODS: Antibodies against three targets (tau, NFL, and NFH) were measured using ELISA in 100 serum samples from 51 cognitively normal elderly controls and 49 patients with AD. Our primary cross-sectional design was further extended to monitor fluctuations over 1-2 years in a subset of individuals. RESULTS: The AD patients had lower levels of anti-tau antibodies (p = 0.03) and even lower anti-NFH antibodies (p = 0.005) than those in the control group at baseline. On the contrary, anti-NFL antibodies or total IgG concentrations in serum did not differ. All three antibodies remained stable in both groups except for a selective and significant anti-tau decline in AD patients (p = 0.03). CONCLUSIONS: The different responses to these antigens suggest some antibody selectivity in AD. The significant decline was observed for only serum anti-tau antibodies in AD patients over time and it corresponds to lower anti-tau levels in these patients. Our findings indicate a special feature of disease-relevant antigens and humoral autoimmunity in AD.

Changes in concentrations of tau-reactive antibodies are dependent on sex in Alzheimer's disease patients.

The presence of pre-existing natural antibodies against Alzheimer's disease (AD) pathological proteins might interfere with immune responses to therapeutic vaccination with these proteins. We aimed to compare levels of antibodies in CSF and serum: We observed higher reactivity of natural tau-reactive antibodies towards phosphorylated bovine tau protein than to human recombinant (non-phosphorylated) tau protein. Males with MCI-AD had higher amounts of these antibodies than corresponding controls. Concentrations of antibodies were lower in females with the MCI-AD than in control females. These findings may have implications for tau vaccination trials.