Spinocerebellar ataxias (SCA) are rare neurodegenerative diseases affecting the cerebellum and its connections, leading to progressive motor disability and cognitive impairment as part of the cerebellar cognitive affective syndrome. Spatial navigation, cognitive function important for everyday movement, relies on spatial perspective taking-the ability to imagine the environment from different viewpoints. While animal and neuroimaging studies suggest a crucial role of the cerebellum in spatial navigation, research on patients with cerebellar disorders is lacking. This study aimed to investigate perspective taking in patients with SCA and Friedreich ataxia (FRDA) using two tests. The Perspective-Taking/Spatial Orientation Test (PTSOT) was administered to 30 SCA patients, 30 FRDA patients, and 34 healthy controls (HC). In addition, SCA and HC completed the Directional-approach Task and a comprehensive neuropsychological assessment. SCA patients performed significantly worse than HC on both perspective taking tests. FRDA patients performed better than SCA and differed from HC only in a subset of PTSOT measures. Perspective taking performance in SCA was associated with global cognition and multiple cognitive domains but not with cerebellar motor impairment. These findings are of potential clinical relevance, as spatial navigation deficits are known to negatively affect the mobility and independence of the affected individuals. Our findings expand the understanding of cognitive impairments in cerebellar diseases, adding spatial navigation to the spectrum of the cerebellar cognitive affective syndrome.

• Klíčová slova
• Cerebellum, Cognition, Friedreich ataxia, Spatial navigation, Spatial perspective taking, Spinocerebellar ataxia,
• MeSH
• dospělí MeSH
• Friedreichova ataxie * patofyziologie   psychologie   MeSH
• kognice MeSH
• kognitivní dysfunkce patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozeček patofyziologie   MeSH
• neuropsychologické testy MeSH
• prostorová navigace * fyziologie   MeSH
• spinocerebelární ataxie * patofyziologie   psychologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: White matter changes assessed by DTI typically reflect tract functionality. This study aimed to investigate DTI parameter alterations in important regions pre- and postshunt implantation in patients with idiopathic normal pressure hydrocephalus (iNPH), alongside assessing the relationship between DTI parameters and clinical improvement. MATERIALS AND METHODS: Patients with probable iNPH underwent prospective preoperative MRI and comprehensive clinical work-up between 2017-2022. Patients with clinical symptoms of iNPH, positive result on a lumbar infusion test, and/or gait improvement after 120-hour lumbar drainage were diagnosed with iNPH and underwent shunt-placement surgery. Fractional anisotropy and mean diffusivity values for individual regions of interest were extracted from preoperative and postoperative MRI. These values were correlated with the clinical picture of individual patients. RESULTS: A total of 32 patients (73.59 ± 4.59 years) with definite iNPH were analyzed. Preoperative DTI characteristics of internal capsule and corona radiata correlated with the 1-year improvement in the Dutch Gait Scale postoperatively (all P < .036). Cognitive domain improvement after surgery in memory and psychomotor speed correlated with preoperative DTI values of cingulate gyrus (P = .050), uncinate fasciculus (P = .029), superior longitudinal fasciculus (P = .020), or corpus callosum (P < .045). CONCLUSIONS: DTI characteristics of white matter regions reflect clinical improvement after shunt surgery in patients with iNPH. They tend to improve toward physiologic DTI values, thus further accentuating the benefit of shunt surgery in both clinical and radiologic pictures.

• MeSH
• anizotropie MeSH
• bílá hmota diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• normotenzní hydrocefalus * chirurgie   diagnostické zobrazování   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shunty pro odvod mozkomíšního moku * MeSH
• výsledek terapie MeSH
• zobrazování difuzních tenzorů * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Maintaining cellular homeostasis by removing damaged and senescent mitochondria, a process termed mitophagy, is crucial in preventing Alzheimer's disease (AD) and represents a promising therapeutic target. Our previous research revealed altered mitophagy biomarkers, such as increased CSF and serum PINK1 and serum BNIP3L and decreased serum TFEB levels, indicating impaired autophagy-lysosomal degradation in the AD continuum. However, the role of autophagy/mitophagy in frontotemporal lobar degeneration (FTLD) remains unclear. This study investigated the biomarkers of autophagy/mitophagy and lysosomal biogenesis (PINK1, ULK1, BNIP3L, and TFEB) in biofluids (CSF and serum) from 308 biomarker-defined individuals across the FTLD continuum (FTLD-dementia, n = 29; FTLD-MCI, n = 33) and compared them with those across the AD continuum (MCI-AD, n = 100; AD-dementia, n = 100) and cognitively unimpaired (CU) controls (n = 46) recruited from Czech Brain Aging Study. Additionally, we compared the mitophagy biomarkers across different FTLD clinical subtypes (frontal, semantic and nonfluent variant) with CU, and explored the association between mitophagy biomarkers and clinical phenotypes of FTLD (biomarkers of tau, biomarkers of neurodegeneration, cognition and ATN profile).Our findings indicated a significantly lower CSF PINK1 and ULK1 levels in FTLD compared to AD, with FTLD dementia showing particularly low CSF PINK1 levels compared to AD-dementia. Conversely, CSF ULK1 levels were higher in FTLD-MCI compared to AD-dementia. Serum analyses revealed lower PINK1 and higher TFEB levels in FTLD dementia compared to AD dementia. This study provides compelling evidence of distinct alterations in autophagy/mitophagy biomarkers between FTLD and AD, indicating that these neurodegenerative diseases may affect the cellular waste disposal system through different pathways. This is the first study to explore mitophagy biomarkers in human CSF and serum in FTLD, opening avenues for further research and potential clinical applications.

• Klíčová slova
• Autophagy, Frontotemporal lobar degeneration, MAPT, Neurocognitive impairment, PINK1, TDP-43, TFEB,
• MeSH
• Alzheimerova nemoc * mozkomíšní mok   metabolismus   patologie   krev   MeSH
• autofagie * fyziologie   MeSH
• biologické markery mozkomíšní mok   krev   MeSH
• frontotemporální lobární degenerace * mozkomíšní mok   metabolismus   patologie   krev   MeSH
• homolog Atg1 mozkomíšní mok   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitofagie * fyziologie   MeSH
• proteinkinasy mozkomíšní mok   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• homolog Atg1 MeSH
• intracelulární signální peptidy a proteiny MeSH
• proteinkinasy MeSH
• PTEN-induced putative kinase MeSH Prohlížeč
• ULK1 protein, human MeSH Prohlížeč

BACKGROUND: There is initial evidence suggesting that biomarker neurogranin (Ng) may distinguish Alzheimer's disease (AD) from other neurodegenerative diseases. Therefore, we assessed (a) the discriminant ability of cerebrospinal fluid (CSF) Ng levels to distinguish between AD and frontotemporal lobar degeneration (FTLD) pathology and between different stages within the same disease, (b) the relationship between Ng levels and cognitive performance in both AD and FTLD pathology, and (c) whether CSF Ng levels vary by apolipoprotein E (APOE) polymorphism in the AD continuum. METHODS: Participants with subjective cognitive decline (SCD) (n = 33), amnestic mild cognitive impairment (aMCI) due to AD (n = 109), AD dementia (n = 67), MCI due to FTLD (n = 25), and FTLD dementia (n = 29) were recruited from the Czech Brain Aging Study. One-way analysis of covariance (ANCOVA) assessed Ng levels in diagnostic subgroups. Linear regressions evaluated the relationship between CSF Ng levels, memory scores, and APOE polymorphism. RESULTS: Ng levels were higher in aMCI-AD patients compared to MCI-FTLD (F[1, 134] = 15.16, p < .001), and in AD-dementia compared to FTLD-dementia (F[1, 96] = 4.60, p = .029). Additionally, Ng levels were higher in FTLD-dementia patients compared to MCI-FTLD (F[1, 54]= 4.35, p = .034), lower in SCD participants compared to aMCI-AD (F[1, 142] = 10.72, p = .001) and AD-dementia (F[1, 100] = 20.90, p < .001), and did not differ between SCD participants and MCI-FTLD (F[1, 58]= 1.02, p = .491) or FTLD-dementia (F[1, 62]= 2.27, p = .051). The main effect of diagnosis across the diagnostic subgroups on Aβ1-42/Ng ratio was significant too (F[4, 263]=, p < .001). We found a non-significant association between Ng levels and memory scores overall (β=-0.25, p = .154) or in AD diagnostic subgroups, and non-significant differences in this association between overall AD APOE ε4 carriers and non-carriers (β=-0.32, p = .358). CONCLUSIONS: In this first study to-date to assess MCI and dementia due to AD or FTLD within one study, elevated CSF Ng appears to be an early biomarker of AD-related impairment, but its role as a biomarker appears to diminish after dementia diagnosis, whereby dementia-related underlying processes in AD and FTLD may begin to merge. The Aβ1-42/Ng ratio discriminated AD from FTLD patients better than Ng alone. CSF Ng levels were not related to memory in AD or FTLD, suggesting that Ng may be a marker of the biological signs of disease state rather than cognitive deficits.

• Klíčová slova
• APOE, Alzheimer’s disease, Frontotemporal lobar degeneration, Memory, Neurogranin,
• MeSH
• Alzheimerova nemoc * mozkomíšní mok   diagnóza   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoproteiny E genetika   mozkomíšní mok   MeSH
• biologické markery * mozkomíšní mok   MeSH
• frontotemporální lobární degenerace * mozkomíšní mok   diagnóza   MeSH
• kognitivní dysfunkce * mozkomíšní mok   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurogranin * mozkomíšní mok   MeSH
• neuropsychologické testy MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• apolipoproteiny E MeSH
• biologické markery * MeSH
• neurogranin * MeSH
• NRGN protein, human MeSH Prohlížeč

Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology.Abbreviation: Aβ: amyloid beta; AD: Alzheimer disease; AVs: autophagic vacuoles; BNIP3L: BCL2 interacting protein 3 like; CU: cognitively unimpaired; CSF: cerebrospinal fluid; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCI: mild cognitive impairment; NRGN: neurogranin; NEFL: neurofilament light chain; p-MAPT/tau: phosphorylated microtubule associated protein tau; PINK1: PTEN induced kinase 1; t-MAPT/tau: total microtubule associated protein tau; TFEB: transcription factor EB; TMT: Trail Making Test.

• Klíčová slova
• Autophagy, BNIP3L, PINK1, TFEB, mild cognitive impairment, mitophagy,
• MeSH
• Alzheimerova nemoc * mozkomíšní mok   krev   diagnóza   MeSH
• biologické markery * mozkomíšní mok   krev   metabolismus   MeSH
• kognitivní dysfunkce mozkomíšní mok   krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny mozkomíšní mok   metabolismus   krev   MeSH
• mitofagie * MeSH
• mozek metabolismus   patologie   MeSH
• nádorové supresorové proteiny MeSH
• proteinkinasy metabolismus   MeSH
• proteiny tau mozkomíšní mok   metabolismus   MeSH
• protoonkogenní proteiny mozkomíšní mok   krev   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktory BHLH-Zip metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery * MeSH
• BNIP3L protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• nádorové supresorové proteiny MeSH
• proteinkinasy MeSH
• proteiny tau MeSH
• protoonkogenní proteiny MeSH
• PTEN-induced putative kinase MeSH Prohlížeč
• TFEB protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip MeSH

We sought to describe the cognitive profile of patients with Idiopathic Normal Pressure Hydrocephalus (iNPH) using a comprehensive neuropsychological battery. Based on age and education correlated norms, we aimed to compare performance in each measured cognitive domain: executive functions (EFs), verbal memory (VM), non-verbal memory (nVM), visuoconstructional abilities (VA) and attention/psychomotor speed (A/PS). Patients diagnosed with iNPH underwent comprehensive neuropsychological evaluation before shunting. Their performance was compared to the age and education correlated norms. Correlation of different cognitive domains in iNPH profile was performed. A total of 53 iNPH patients (73.21 ± 5.48 years) were included in the study. All of the measured cognitive domains were significantly damaged. The most affected domains were EFs and VM (p<0.001 and p<0.001, respectively). A/PS domain was affected milder than EFs and VM (p<0.001). The least affected domains were nVM (p<0.001) and VA (p<0.001). Patients with iNPH are affected in all cognitive domains and the cognitive decline is uneven across these domains. The impairment of memory was shown to depend on the presented material. VM was shown to be much more severely affected than nVM and along with VM, EFs were shown to be the most affected. A/PS speed was shown to be less affected than VM and EFs and the least affected domains were nVM and VA.

• Klíčová slova
• Cognitive decline, executive functions, Neuropsychology, Normal pressure hydrocephalus,
• MeSH
• exekutivní funkce MeSH
• kognice MeSH
• kognitivní dysfunkce * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• normotenzní hydrocefalus * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.

• Klíčová slova
• Aging, Default mode network, Directed functional connectivity MRI, Multivariate analysis, Neuropsychological tests,
• MeSH
• krátkodobá paměť MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mapování mozku * metody   MeSH
• mozek * diagnostické zobrazování   MeSH
• nervové dráhy MeSH
• senioři MeSH
• stárnutí MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. METHODS: Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3 T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. RESULTS: VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. CONCLUSIONS: iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.

• Klíčová slova
• Cognition, Mild cognitive impairment, Prodromal, REM sleep without atonia, Synucleinopathy, Trail Making Test,
• MeSH
• kognice MeSH
• kognitivní dysfunkce * diagnostické zobrazování   komplikace   MeSH
• lidé MeSH
• mozeček MeSH
• porucha chování v REM spánku * diagnostické zobrazování   komplikace   MeSH
• spánkový lalok MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Studies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters. METHODS: Using a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments. RESULTS: In young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education. DISCUSSION: The flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.

• Klíčová slova
• aging, dedifferentiation, functional connectivity, multivariate analysis, neuropsychological tests, the impaired GABA theory,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The study worked with depressive symptoms, anxiety score and cognitive functions in obstructive sleep apnea (OSA) patients treated with CPAP. METHODS: Eighty-one subjects with OSA and without psychiatric comorbidity were treated with CPAP for one year and completed the following scales and cognitive tests: Trail Making Test, Verbal Fluency Test, d2 Test, Beck Depression Inventory-II and Beck Anxiety Inventory. MINI ruled out psychiatric disorder. At the two months check-up, subjects were re-evaluated for depressive and anxiety symptoms, and after one year of CPAP treatment, subjects repeated cognitive tests and scales. Data about therapy adherence and effectiveness were obtained from the patient's CPAP machines. RESULTS: The study was completed by 59 CPAP adherent patients and eight non-adherent patients. CPAP therapy effectiveness was verified in all patients by decreasing the apnea-hypopnoea index below 5 and/or 10% of baseline values. The adherent patients significantly improved depressive and anxiety symptoms. There was also an improvement in overall performance in the attention test; however, performance in many individual items did not change. The adherent patients also improved verbal fluency and in the Part B of the Trail making test. The non-adherent group significantly increased the number of mistakes made in the d2 test; other results were non-significant. CONCLUSION: According to our results, OSA patients' mood, anxiety and certain cognitive domains improved during the one-year therapy with CPAP. TRIAL REGISTRATION NUMBER: NCT03866161.

• Klíčová slova
• CPAP treatment, Trail Making Test, Verbal Fluency Test, cognitive functions, depression, obstructive sleep apnoea, treatment efficacy,
• Publikační typ
• časopisecké články MeSH