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
- Alzheimer Disease genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Cognitive Dysfunction * genetics MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Neuropsychological Tests MeSH
- ATP Binding Cassette Transporter, Subfamily B genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic 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
- Immunotherapy, Active methods MeSH
- Alzheimer Disease * blood therapy immunology MeSH
- Biomarkers blood MeSH
- Double-Blind Method MeSH
- Middle Aged MeSH
- Humans MeSH
- tau Proteins * blood MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Mental Status and Dementia Tests MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial 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
- Adult MeSH
- Cognitive Dysfunction * diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Trail Making Test statistics & numerical data MeSH
- Walk Test * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Clinical Study 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
- Alzheimer Disease * cerebrospinal fluid diagnosis MeSH
- Amyloid beta-Peptides cerebrospinal fluid MeSH
- Apolipoproteins E genetics cerebrospinal fluid MeSH
- Biomarkers * cerebrospinal fluid MeSH
- Frontotemporal Lobar Degeneration * cerebrospinal fluid diagnosis MeSH
- Cognitive Dysfunction * cerebrospinal fluid diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Neurogranin * cerebrospinal fluid MeSH
- Neuropsychological Tests MeSH
- Cross-Sectional Studies 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
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
- Depressive Disorder, Major * MeSH
- Adult MeSH
- Consensus MeSH
- Quality of Life MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Cerebellum pathology MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Aging MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Review 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
- Alzheimer Disease diagnostic imaging pathology MeSH
- Atrophy * pathology MeSH
- Dementia * diagnostic imaging pathology MeSH
- Cognitive Dysfunction * diagnostic imaging pathology diagnosis MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain * pathology diagnostic imaging MeSH
- Neuropsychological Tests MeSH
- Disease Progression * 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
- Research Support, Non-U.S. Gov't MeSH
Subjektívny pokles kognície je koncept, ktorý označuje jedincom subjektívne pociťované zhoršenie kognitívnych funkcií v čase, pričom v neuropsychologickom vyšetrení nie je identifikovaný objektívne znížený výkon. Tento koncept bol zavedený a skúmaný primárne v kontexte Alzheimerovej choroby a môže byť súčasťou kontinua neurodegeneratívnych ochorení. Cieľom prehľadovej štúdie je opísať koncept subjektívneho kognitívneho poklesu s dôrazom na jeho prediktívnu validitu vo vzťahu k rozvoju miernej kognitívnej poruchy a demencie. Štúdia analyzuje taktiež vzťahy subjektívneho poklesu kognície s inými faktormi, ako sú somatické ochorenia, poruchy nálady, úzkosť a osobnostné faktory. V závere štúdie sú formulované postupy pre odborníkov, ktoré na základe posúdenia subjektívneho poklesu kognície a jeho kritérií autori odporúčajú u pacienta zrealizovať.
Subjective cognitive decline is a concept that refers to a subjectively perceived decline in cognitive functioning over time, despite no objectively identified decreased performance in neuropsychological testing. This concept was primarily introduced and studied in the context of Alzheimer’s disease and may be a part of the continuum of neurodegenerative diseases. The aim of the review study is to describe the concept of subjective cognitive decline, with a focus on its predictive validity in relation to the development of mild cognitive impairment and dementia. The study also analyzes the relationships between subjective cognitive decline and other factors, such as somatic illnesses, mood disorders, anxiety, and personality factors. In conclusion, the study formulates procedures for professionals that are recommended based on the assessment of subjective cognitive decline and its criteria.
INTRODUCTION: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments. METHODS: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau181, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma Aβ42 and Aβ40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau181 at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test. RESULTS: The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau181 reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks. CONCLUSIONS: The effect of ALZ-801 on reducing plasma p-tau181 over 2 years demonstrates target engagement and supports its anti-Aβ oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04693520 .
- MeSH
- Alzheimer Disease * drug therapy diagnostic imaging MeSH
- Amyloid beta-Peptides * MeSH
- Administration, Oral MeSH
- Apolipoprotein E4 * genetics MeSH
- Biomarkers * blood MeSH
- Heterozygote MeSH
- Hippocampus * drug effects diagnostic imaging MeSH
- Cognition * drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Peptide Fragments blood MeSH
- tau Proteins 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
- Clinical Trial, Phase II MeSH
Impaired spatial navigation is early marker of Alzheimer's disease (AD). We examined ability of self- and informant-reported navigation questionnaires to discriminate between clinically and biomarker-defined participants, and associations of questionnaires with navigation performance, regional brain atrophy, AD biomarkers, and biomarker status. 262 participants (cognitively normal, with subjective cognitive decline, amnestic mild cognitive impairment [aMCI], and mild dementia) and their informants completed three navigation questionnaires. Navigation performance, magnetic resonance imaging volume/thickness of AD-related brain regions, and AD biomarkers were measured. Informant-reported questionnaires distinguished between cognitively normal and impaired participants, and amyloid-β positive and negative aMCI. Lower scores were associated with worse navigation performance, greater atrophy in AD-related brain regions, and amyloid-β status. Self-reported questionnaire scores did not distinguish between the groups and were weakly associated with navigation performance. Other associations were not significant. Informant-reported navigation questionnaires may be a screening tool for early AD reflecting atrophy of AD-related brain regions and AD pathology.
- Publication type
- Journal Article MeSH
BACKGROUND: Functional connectivity changes in clinically overt neurodegenerative diseases such as dementia with Lewy bodies have been described, but studies on connectivity changes in the pre-dementia phase are scarce. OBJECTIVES: We concentrated on evaluating striato-cortical functional connectivity differences between patients with Mild Cognitive Impairment with Lewy bodies and healthy controls and on assessing the relation to cognition. METHODS: Altogether, we enrolled 77 participants (47 patients, of which 35 met all the inclusion criteria for the final analysis, and 30 age- and gender-matched healthy controls, of which 28 met all the inclusion criteria for the final analysis) to study the seed-based connectivity of the dorsal, middle, and ventral striatum. We assessed correlations between functional connectivity in the regions of between-group differences and neuropsychological scores of interest (visuospatial and executive domains z-scores). RESULTS: Subjects with Mild Cognitive Impairment with Lewy Bodies, as compared to healthy controls, showed increased connectivity from the dorsal part of the striatum particularly to the bilateral anterior part of the temporal cortex with an association with executive functions. CONCLUSIONS: We were able to capture early abnormal connectivity within cholinergic and noradrenergic pathways that correlated with cognitive functions known to be linked to cholinergic/noradrenergic deficits. The knowledge of specific alterations may improve our understanding of early neural changes in pre-dementia stages and enhance research of disease modifying therapy.
