BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• MeSH
• alpha-Synuclein metabolism   MeSH
• Lewy Body Disease * diagnostic imaging   pathology   MeSH
• Cognitive Dysfunction * diagnostic imaging   pathology   physiopathology   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Locus Coeruleus * diagnostic imaging   pathology   MeSH
• Magnetic Resonance Imaging * MeSH
• Neuropsychological Tests MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. METHODS: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. RESULTS: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896. CONCLUSIONS: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models.

• MeSH
• Alzheimer Disease * economics   drug therapy   MeSH
• Cost-Benefit Analysis * MeSH
• Models, Economic MeSH
• Cognitive Dysfunction * economics   MeSH
• Quality-Adjusted Life Years MeSH
• Humans MeSH
• Decision Support Techniques MeSH
• Disease Progression MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

• MeSH
• Adult MeSH
• Cognitive Dysfunction etiology   physiopathology   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Cross-Sectional Studies MeSH
• Multiple Sclerosis * complications   diagnostic imaging   physiopathology   MeSH
• Processing Speed MeSH
• Fatigue * physiopathology   etiology   diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Alzheimerova choroba je nejčastější příčinou demence a včasná diagnostika je klíčová pro zahájení léčby. Porucha čichu, zejména schopnost identifikace pachů, byla opakovaně identifikována jako raný příznak neurodegenerativních změn a může pomoci při časné detekci Alzheimerovy choroby. Psychofyzické testy čichu, jako je Sniffin’ Sticks, (SST) University of Pennsylvania Smell Identification Test (UPSIT), či test parfémovaných fixů (OMT), jsou spolehlivými nástroji pro hodnocení čichových funkcí a mají potenciál doplnit tradiční neuropsychologické testy. Kombinace čichových a kognitivních testů významně zvyšuje přesnost predikce nástupu demence.

Koutná V, Štěpánek L, Trajerová R, Janout V, Janoutová J. Olfactory impairment as a biomarker in early diagnosis of Alzheimer’s disease in primary care Alzheimer’s disease is the most common cause of dementia and early diagnosis is key to initiating treatment. Olfactory dysfunction, particularly the ability to discriminate odors, has been repeatedly identified as an early sign of neurodegenerative changes and may aid in the early detection of Alzheimer’s disease. Psychophysical olfactory tests such as the Sniffin’ Sticks (SST), University of Pennsylvania Smell Identification Test (UPSIT) or the Odorized Marker Test (OMT) are reliable tools for assessing olfactory function and have potential to complement traditional neuropsychological tests. The combination of olfactory and cognitive tests significantly increases the accuracy of predicting the onset of dementia.

INTRODUCTION: Chitinase-3-like protein 1 (CHI3L1) is a glycoprotein implicated in various neurological conditions. It is associated with neuroinflammation and tissue remodeling. The study aimed to validate the reference interval (RI) of serum (S) CHI3L1 in a control group, to correlate S CHI3L1 values with other biomarkers of neurodegenerative damage, and to estimate the diagnostic accuracy of S CHI3L1. METHODS: Samples from 108 healthy volunteers were used to estimate the S CHI3L1 RI. For the comparison, we used cerebrospinal fluid (CSF) and serum (S) samples from 121 patients with cognitive disorders, and cognitive deterioration was assessed using the Mini-Mental State Examination (MMSE). ELISA assays were used to determine the S CHI3L1, CSF, and S neurofilament light chain (NfL) levels; CSF and plasma β-amyloid peptide42; CSF and plasma β-amyloid peptide40; CSF total tau protein; CSF phosphorylated tau protein; and CSF alpha-synuclein. RESULTS: The estimated RI of S CHI3L1 was 14.44 to 63.11 μg/L. The cut-off value of S CHI3L1 was 34.37 μg/L. ROC analysis showed that S CHI3L1 has 81.4% sensitivity and 76.9% specificity. We found a moderate Spearman's rank correlation coefficient between the S CHI3L1 and age (rS = 0.486; p < 0.001) and between S CHI3L1 and S NfL (rS = 0.489; p < 0.001) in all groups. The Kruskal-Wallis test showed a significant overall difference in S CHI3L1 among diagnostic groups (p = 0.013). S CHI3L1 and CSF NfL had statistically significant effects on MMSE values (multiple R2 was 0.431). CONCLUSIONS: Our results suggest that S CHI3L1 reflects the severity of cognitive deficits assessed by MMSE. It can be used as a supportive biomarker in neurodegenerative diseases.

• MeSH
• alpha-Synuclein cerebrospinal fluid   blood   MeSH
• Amyloid beta-Peptides blood   cerebrospinal fluid   MeSH
• Biomarkers blood   cerebrospinal fluid   MeSH
• Adult MeSH
• Cognitive Dysfunction * blood   cerebrospinal fluid   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neurofilament Proteins cerebrospinal fluid   blood   MeSH
• Movement Disorders * blood   cerebrospinal fluid   diagnosis   MeSH
• Chitinase-3-Like Protein 1 * blood   cerebrospinal fluid   MeSH
• tau Proteins cerebrospinal fluid   blood   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Cognitive flexibility (CF) is the ability to adapt cognitive strategies according to the changing environment. The deficit in CF has often been linked to various neurological and psychiatric disorders including schizophrenia. However, the operationalization and assessment of CF have not been unified and the current research suggests that the available instruments measure different aspects of CF. The main objective of the present study was to compare three frequently used neuropsychological measures of CF-Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Color and Word Test (SCWT) in a population of patients (N = 220) with first-episode schizophrenia spectrum disorders in order to evaluate their convergent validity. The hypothesis of an underlying latent construct was tested via a confirmatory factor analysis. We used a one-factor CF model with scores from WCST, SCWT and TMT as observed variables. The established model showed a good fit to the data (χ2 = 1.67, p = 0.43, SRMR = 0.02, RMSEA = 0.0, CFI = 1.00). The highest factor loading was found in WCST as CF explained most of the variance in this neuropsychological measure compared to the other instruments. On the other hand, a TMT ratio index and a SCWT interference demonstrated lowest loadings in the model. The findings suggest that not all the frequently used measures share an underlying factor of CF or may capture different aspects of this construct.

• MeSH
• Adult MeSH
• Executive Function * physiology   MeSH
• Factor Analysis, Statistical MeSH
• Cognitive Dysfunction * etiology   diagnosis   physiopathology   MeSH
• Cognitive Flexibility MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Neuropsychological Tests * standards   MeSH
• Psychometrics MeSH
• Schizophrenic Psychology * MeSH
• Schizophrenia * complications   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Obezita a diabetes mellitus 2. typu (DM2T) sú významnými rizikovými faktormi rozvoja kognitívnej dysfunkcie a neurodegeneratívnych ochorení. Ich spoločný patofyziologický základ zahŕňa inzulínovú rezistenciu, chronický subklinický systémový zápal a neurozápal, poruchy mikrobiómu, hormonálnu dysreguláciu a štrukturálne zmeny mozgu. Tieto faktory vedú k zhoršeniu pamäte, exekutívnych funkcií a k akcelerácii neurodegenerácie. Pozitívne účinky úpravy životného štýlu – vrátane zníženia telesnej hmotnosti, zvýšenia fyzickej aktivity a úpravy výživy a stravovacích návykov – sa prejavujú zlepšením inzulínovej senzitivity v mozgu, zvýšením neurotrofických faktorov, redukciou systémového zápalu a neurozápalu a zlepšením metabolizmu. Kombinácia behaviorálnych a farmakologických intervencií môže spomaliť kognitívny pokles a znížiť riziko demencie u populácie s obezitou a poruchou metabolizmu glukózy.

Obesity and type 2 diabetes (T2D) are important risk factors for the development of cognitive dysfunction and neurodegenerative diseases. Their common pathophysiological substrate includes insulin resistance, chronic subclinical systemic inflammation, neuroinflammation, shifts in the intestinal microbiome composition, hormonal dysregulation, and structural changes of the brain. These factors lead to impaired memory, executive functions, and accelerated neurodegeneration. The positive effects of lifestyle modifications — including weight loss, increased physical activity, and improved dietary composition — are manifested by improved insulin sensitivity in the brain, increased neurotrophic factors, reduced systemic inflammation and neuroinflammation, and improved metabolism. A combination of behavioral and pharmacological interventions may slow cognitive decline and reduce the risk of dementia in patients with obesity, prediabetes and T2D.

• MeSH
• Exercise MeSH
• Diabetes Mellitus, Type 2 complications   MeSH
• Weight Loss MeSH
• Cognition Disorders * etiology   MeSH
• Humans MeSH
• Neurodegenerative Diseases etiology   MeSH
• Obesity * complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Poruchy autistického spektra jsou pervazivní vývojové poruchy. Ovlivněny jsou tak v podstatě všechny složky vývoje již od raného věku. Rodiče si všímají odlišností ze- jména v sociální oblasti, děti často nesdílejí pozornost, nekomunikují a nesdělují svoje potřeby a přání. Již ve věku 18 měsíců se dělá screening M-CHAT-R, který může zachytit nápadnosti ve vývoji (možné neurovývojové poruchy) a pediatr může rodiče směřovat k odborníkům – klinickým psychologům zaměřujícím se na práci s dětmi s PAS (poruchou autistického spektra), pedopsychiatrovi, dětskému neurologovi či specializovanému klinickému logopedovi. V tomto článku vám představíme kazuistiku s diferenciální diagnostikou odlišující PAS od dalších vývojových poruch (zejména vývojové dysfázie) a zaměřenou na stanovení stupně symptomů v kontextu poruch autistického spektra. Je to jedna z typických diferenciálních diagnostik, které na Soukromé klinice LOGO, s.r.o. děláme.

Autism Spectrum Disorders are pervasive developmental disorders. This means that they influence almost all areas of early development. Parents can see differences mainly in the social area. Children with ASD do not share activities, do not communicate their needs and wishes. At the age of 18 months, parents fill in the M-CHAT-R screening, which is sensitive to possible neurodevelopmental problems. A paediatrician can send the child to specialists in ASD diagnosis - clinical psychologist, child psychiatrist, neurologist and clinical speech therapist. In this article, we introduce you to a case study with differential diagnoses, showing the differences between Autism Spectrum Disorders and other developmental diseases (especially specific developmental disorders of speech and language). The focus is on the determination of the autistic symptoms level. This is one of the typical differential diagnoses we carry out at LOGO Clinic.

• MeSH
• Cognitive Dysfunction diagnosis   MeSH
• Communication Disorders diagnosis   MeSH
• Humans MeSH
• Autism Spectrum Disorder * diagnosis   psychology   MeSH
• Child, Preschool MeSH
• Psychological Tests MeSH
• Stereotyped Behavior MeSH
• Language Development Disorders diagnosis   MeSH
• Developmental Disabilities diagnosis   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Publication type
• Case Reports MeSH

In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.

• MeSH
• Biological Evolution MeSH
• Pain * metabolism   physiopathology   MeSH
• Exercise * physiology   MeSH
• Energy Metabolism * MeSH
• Cognition * physiology   MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Motivation * MeSH
• Pleasure * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• MeSH
• Alzheimer Disease * genetics   cerebrospinal fluid   diagnostic imaging   complications   physiopathology   pathology   MeSH
• Amyloid beta-Peptides cerebrospinal fluid   MeSH
• Apolipoprotein E4 * genetics   MeSH
• Apolipoproteins E * genetics   MeSH
• Atrophy MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Genotype MeSH
• Cognitive Dysfunction * genetics   cerebrospinal fluid   diagnostic imaging   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain pathology   diagnostic imaging   MeSH
• Neuropsychological Tests MeSH
• Peptide Fragments cerebrospinal fluid   MeSH
• Positron-Emission Tomography MeSH
• Spatial Navigation * physiology   MeSH
• tau Proteins cerebrospinal fluid   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH