The ABCB1 gene, encoding the ATP-dependent translocase ABCB1, plays a crucial role in the clearance of amyloid-beta (Aβ) peptides and the transport of cholesterol, implicating it in the pathogenesis of Alzheimer's disease. The study aims to investigate the association between polymorphisms in the ABCB1 gene and cognitive decline in individuals with mild cognitive impairment (MCI), particularly focusing on language function. A longitudinal cohort study involving 1 005 participants from the Czech Brain Aging Study was conducted. Participants included individuals with Alzheimer's disease, amnestic MCI, non-amnestic MCI, subjective cognitive decline, and healthy controls. Next-generation sequencing was utilized to analyze the entire ABCB1 gene. Cognitive performance was assessed using a comprehensive battery of neuropsychological tests, including the Boston Naming Test and the semantic verbal fluency test. Ten ABCB1 polymorphisms (rs55912869, rs56243536, rs10225473, rs10274587, rs2235040, rs12720067, rs12334183, rs10260862, rs201620488, and rs28718458) were significantly associated with cognitive performance, particularly in language decline among amnestic MCI patients. In silico analyses revealed that some of these polymorphisms may affect the binding sites for transcription factors (HNF-3alpha, C/EBPβ, GR-alpha) and the generation of novel exonic splicing enhancers. Additionally, polymorphism rs55912869 was identified as a potential binding site for the microRNA hsa-mir-3163. Our findings highlight the significant role of ABCB1 polymorphisms in cognitive decline, particularly in language function, among individuals with amnestic MCI. These polymorphisms may influence gene expression and function through interactions with miRNAs, transcription factors, and alternative splicing mechanisms.

• MeSH
• Alzheimerova nemoc genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kognitivní dysfunkce * genetika   MeSH
• lidé MeSH
• longitudinální studie MeSH
• neuropsychologické testy MeSH
• P-glykoproteiny genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Cíl: Montrealský kognitivní test (MoCA) je jednou z nejpoužívanějších screeningových zkoušek kognice u dospělých osob, pro něž existují normy pro českou populaci. Varianta MoCA-22, která je určena pro osoby s poruchami zraku či imobilitou horních končetin, se dá administrovat i po telefonu. Tato studie přináší české normy MoCA-22. Materiál a metodika: Soubor (n = 1 049) se skládá z účastníků čtyř studií provedených v ČR. Zařazeny byly osoby ve věku 19–98 let, bez neurodegenerativního, psychiatrického či jiného závažného onemocnění. Data pro MoCA-22 byla odvozena z dat získaných vyšetřením standardní verzí MoCA. V souladu se zavedenou klinickou praxí i statistickou analýzou jsou soubor a odvozené normy rozděleny na tři věkové kategorie: 19–50 let, 51–74 let, 75 a více let. Výsledky: Pro výše uvedené věkové kategorie dále rozdělené dle dosaženého vzdělání (nižší, vyšší) předkládáme průměrné skóry i odhadované percentilové hranice. Výkon v MoCA-22 je ovlivněn dosaženým vzděláním a věkem, ale nikoli pohlavím. Pro úpravu výsledků dle demografických faktorů proto poskytujeme i regresní rovnici. Závěr: Normativní údaje pro MoCA-22 rozšíří klinické instrumentárium v Česku a umožní adekvátní screening kognice u osob, jež jsou zdravotním stavem limitovány při využití standardních metod.

Aim: The Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in adults with reference standards for the Czech population. The MoCA-22 variant is designed for individuals with visual impairment or upper limb immobility and can be administered over the telephone. This study presents the Czech MoCA-22 normative standards. Materials and methods: The sample (N = 1,049) consists of participants from four studies conducted in the Czech Republic. The subjects included were aged 19–98 years, and were without neurodegenerative, psychiatric, or other serious illness. Data for the MoCA-22 were derived from data obtained by the standard version of MoCA. Following established clinical practice and statistical analysis, the population and derived norms are divided into three age categories: 19–50 years, 51–74 years, and 75 years and older. Results: For these age categories above, which were further subdivided by educational status (lower, higher), we present mean scores and estimated percentile thresholds. Performance in the MoCA-22 is affected by demoraphic factors, such as educational status and age but not sex, as reflected by the regression equation. Conclusions: Normative data for MoCA-22 will complement the clinical armamentarium in Czechia and allow adequate cognitive screening in people whose health status limits them when using standard methods.

• Klíčová slova
• Montrealský kognitivní test (MoCA),
• MeSH
• klinická studie jako téma MeSH
• kognitivní poruchy diagnóza   MeSH
• lidé MeSH
• neuropsychologické testy * normy   MeSH
• osoby upoutané na lůžko MeSH
• telefon MeSH
• telemedicína MeSH
• zrakově postižení MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes. METHODS: ADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study - Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD. RESULTS: Among 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels. CONCLUSIONS: These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial. TRIAL REGISTRATION: EudraCT 2015-000630-30 (primary) and NCT02579252.

• MeSH
• aktivní imunoterapie metody   MeSH
• Alzheimerova nemoc * krev   terapie   imunologie   MeSH
• biologické markery krev   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• proteiny tau * krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testy pro posouzení mentálních funkcí a demence MeSH
• výsledek terapie 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
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Úvod: Včasná detekce pomocí platných screeningových nástrojů může představovat příležitost k odhalení mírné kognitivní poruchy (mild cognitive impairment; MCI) jako rizikového faktoru demence a tím zpomalit progresi kognitivního poklesu u starších dopělích. Cíl: Cílem této studie bylo vyhodnotit Trail Walking Test (TWT) k detekci pravděpodobné MCI (probable MCI; pMCI) u starších jedinců a zhodnotit jeho použitelnost jako screeningového nástroje. Metodika: Studie se zúčastnilo 61 osob rozdělených pomocí Montrealského kognitivního testu (Montreal Cognitive Assessment; MoCA) do tří skupin: starší dospělí s intaktními kognitivními funkcemi (ICA, MoCA > 25); starší dospělí s pMCI (MoCA ≤ 25); a kontrolní skupina mladých jedinců (healthy young adults; HYA). Všichni účastníci absolvovali Trail Making Test a tři varianty TWT se zvyšující se složitostí. Plocha pod křivkou (area under the curve; AUC), senzitivita, specificita a Youdenovy indexy byly použity k vyhodnocení schopnosti každého testu předpovídat projev pravděpodobné mírné kognitivní poruchy u starších jedinců. Na korekciu optimizmu predikcie bola vykonaná interná validácia AUC a vypočítala sa príslušná korigovaná AUC (AUCVAL). Výsledky: Skupina pMCI dosáhla významně horších výsledků ve všech hodnocených variantách TMT a TWT než skupiny ICA a HYA (p < 0,001). Zjistili jsme, že všechny verze testů TMT (např. TMT-A a TMT-B) a TWT (např. TWT-1,2,3) mají velmi dobrou detekční schopnost rozlišení osob s pMCI od kontrolních skupin ICA a HYA hodnocené dohromady s hodnotami AUC v rozmezí od 0,81 do 0,876, které se obecně zvyšují s rostoucí složitostí duálního úkolu. Nejlepší detekční schopnosti však bylo dosaženo, když byla jako kontrolní skupina použita pouze HYA (AUC: 0,894–0,975). Screeningové testy TMT pro detekci pMCI zůstaly validní i po korekcích pomocí bootstrappingu (AUCs: 0,829–0,839). Zatímco varianta testu TWT-2 vykazovala přínos oproti TWT-1, přidaná hodnota TWT-3 oproti TWT-2 byla v naší studii omezená. Závěr: TWT je platným nástrojem pro screening pMCI u starších dospělých. Jeho použití může zlepšit včasnou detekci pMCI v klinických i neklinických podmínkách. Zatímco zvyšující se složitost testu zvyšuje jeho prediktivní výkonnost, na základě našich zjištění se zdá, že existuje hranice, za kterou se přidaná hodnota složitějších duálních úloh snižuje.

Background: Early detection of mild cognitive impairment (MCI) as a risk factor for dementia using valid screening tools can present an opportunity for timely intervention to slow the progression of cognitive decline in older adults. Aim: The aim of this study was to evaluate the Trail Walking Test (TWT) that includes a dual task to predict probable MCI (pMCI) in older adults and to evaluate its usability as a screening tool. Methods: The study was conducted on a sample of 61 subjects categorized using the Montreal Cognitive Assessment (MoCA) into three groups: older adults with intact cognitive ability (ICA, MoCA > 25); older adults with pMCI (MoCA ≤ 25); and “healthy young adults (HYA) ”. All participants completed the Trail Making Test (TMT) and three variants of the TWT with increasing complexity. Area under the receiver operating curve (AUC), sensitivity, specificity and Youden indices were used to evaluate the capacity of each test to predict pMCI in older adults. Internal validation was performed to calculate AUCs corrected for optimism (AUCVAL). Results: The pMCI group performed significantly worse in all evaluated variations of the TMT and TWT than the ICA and HYA groups (P < 0.001). We found that all versions of the TMT (e. g., TMT-A and TMT-B) and TWT tests (e. g., TWT-1, 2, 3) have very good ability to discriminate between people with pMCI and all controls (e. g., ICA and HYA combined) with AUCs ranging from 0.81 to 0.876, generally increasing with increasing complexity of the dual task. Best performance was achieved when only HYA were used as a control group (AUCs: 0.894–0.975). The validity of these tools to predict pMCI remained very good after corrections using bootstrapping (AUCs: 0.829–0.839). While TWT-2 showed more benefits over TWT-1, the added value of TWT-3 over TWT-2 has been limited in this study. Conclusions: The dual component TWT is a valid screening tool for pMCI in older adults. Its use may improve early detection of pMCI in clinical and non-clinical settings. While increasing complexity of the test increases its predicting performance, based on our findings there seems to be a cutoff beyond which the added value of more complex dual tasks diminishes.

• MeSH
• dospělí MeSH
• kognitivní dysfunkce * diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• test cesty statistika a číselné údaje   MeSH
• test chůzí * metody   statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies.

• MeSH
• biologické markery krev   MeSH
• chronicko-progresivní roztroušená skleróza * terapie   diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• progrese nemoci * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Aging populations face significant cognitive challenges, particularly in working memory (WM). Transcranial alternating current stimulation (tACS) offer promising avenues for cognitive enhancement, especially when inspired by brain physiology. This study (NCT04986787) explores the effect of multifocal tACS on WM performance in healthy older adults, focusing on fronto-parietal network modulation. Individualized physiology-inspired tACS applied to the fronto-parietal network was investigated in two blinded cross-over experiments. The first experiment involved monofocal/bifocal theta-tACS to the fronto-parietal network, while in the second experiment cross-frequency theta-gamma interactions between these regions were explored. Participants have done online WM tasks under the stimulation conditions. Network connectivity was assessed via rs-fMRI and multichannel electroencephalography. Prefrontal monofocal theta tACS modestly improved WM accuracy over sham (d = 0.30). Fronto-parietal stimulation enhanced WM task processing speed, with the strongest effects for bifocal in-phase theta tACS (d = 0.41). Cross-frequency stimulations modestly boosted processing speed with or without impairing task accuracy depending on the stimulation protocol. This research adds to the understanding of physiology-inspired brain stimulation for cognitive enhancement in older subjects.

• Publikační typ
• časopisecké články MeSH

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.

• 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

INTRODUCTION: One of the most debilitating problems encountered by people with multiple sclerosis (MS) is the loss of balance and coordination. Our study aimed to comprehensively evaluate the effectiveness of one year of Tai-chi exercise in patients with MS using both subjective and objective methods, including posturography. METHODS: This was a single-group longitudinal one-year study performed from the 1st of January 2019 to the 1st of January 2020. The primary outcomes of interest were the Mini-Balance Evaluation Systems Test (Mini-BESTest) and static posturography measures as objective methods to detect subtle changes associated with postural control/balance impairment. Secondary outcomes were measures of depression, anxiety, cognitive performance, and quality of life. All objective and subjective parameters were assessed four times: at baseline, and after three, six and 12 months of regular Tai-chi training. The difference was calculated as a subtraction of baseline values from every timepoint value for each measurement. If the normality test was passed, parametric one-sample t-test was used, if failed, Wilcoxon signed ranks test was used to test the difference between the baseline and each timepoint. Alpha was set to 0.017 using Bonferroni correction for multiple comparisons. RESULTS: Out of 25 patients with MS enrolled, 15 women with MS (mean age 44.27 years) were included for statistical analyses after completing the 12-month program. After 12 months, significant improvements were found in all objective balance and gait tests: Mini-BESTest (p<0.001), static posturography measures (total area of the centre of foot pressure - TA; p = 0.015), 25 Feet Walk Test (25FWT; p = 0.001), anxiety (Beck Anxiety Inventory - BAI; p = 0.005) and cognition tests (Paced Auditory Serial Addition Test - PASAT; p = 0.003). Measures of depression (Beck Depression Inventory - BDI; p = 0.071), cognition (Symbol Digit Modalities Test - SDMT; p = 0.079), and health-related quality of life (European Quality of Life 5-Dimensions Questionnaire - EQ-5D-5L; p = 0.095) showed a trend of improvement but were not significant, which could be the result of a small sample and increased bias due the type II error. CONCLUSION: According to these preliminary results, this study indicates the possible beneficial effects of long-term Tai-chi training on patients with MS. Although these findings need to be confirmed by further studies with a larger sample of participants of both genders and require more rigorous randomized controlled trials (RCT) design, our findings support the recommendation of regular and long-term Tai-chi exercise in patients with MS. GOV IDENTIFIER (RETROSPECTIVELY REGISTERED): NCT05474209.

• MeSH
• dospělí MeSH
• kognice MeSH
• kvalita života MeSH
• lidé MeSH
• posturální rovnováha MeSH
• prospektivní studie MeSH
• roztroušená skleróza * komplikace   terapie   MeSH
• taiči * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• MeSH
• depresivní porucha unipolární * MeSH
• dospělí MeSH
• konsensus MeSH
• kvalita života MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozeček patologie   MeSH
• průřezové studie MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the 'severity index' generated using a standard classification model trained on patients with AD dementia versus a new model trained on β-amyloid (Aβ) positive patients with amnestic mild cognitive impairment (aMCI). METHODS: We used structural MRI data of 504 patients from the Swedish BioFINDER-1 study cohort (cognitively normal (CN), Aβ-negative = 220; SCD, Aβ positive and negative = 139; aMCI, Aβ-positive = 106; AD dementia = 39). We applied multivariate data analysis to create two predictive models trained to discriminate CN individuals from either individuals with Aβ positive aMCI or AD dementia. Models were applied to individuals with SCD to classify their atrophy patterns as either high-risk "disease-like" or low-risk "CN-like". Clinical trajectory and model accuracy were evaluated using 8 years of longitudinal data. RESULTS: In predicting progression from SCD to MCI or dementia, the standard, dementia-based model, reached 100% specificity but only 10.6% sensitivity, while the new, aMCI-based model, reached 72.3% sensitivity and 60.9% specificity. The aMCI-based model was superior in predicting progression from SCD to MCI or dementia, reaching a higher receiver operating characteristic area under curve (AUC = 0.72; P = 0.037) in comparison with the dementia-based model (AUC = 0.57). CONCLUSION: When predicting conversion from SCD to MCI or dementia using structural MRI data, prediction models based on individuals with milder levels of atrophy (i.e. aMCI) may offer superior clinical value compared to standard dementia-based models.

• MeSH
• Alzheimerova nemoc diagnostické zobrazování   patologie   MeSH
• atrofie * patologie   MeSH
• demence * diagnostické zobrazování   patologie   MeSH
• kognitivní dysfunkce * diagnostické zobrazování   patologie   diagnóza   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• progrese nemoci * 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