Alzheimer's & Dementia最新文献

Introduction: Language complaints in cognitively unimpaired (CU) individuals may reflect Alzheimer's Disease (AD) pathology and future objective impairments.

Methods: 211 participants (138 CU, 45 with mild cognitive impairment (MCI), and 28 with dementia) from the TRIAD cohort underwent ¹⁸F-MK-6240 tau-PET and ¹⁸F-AZD-4694 amyloid-PET. Word-finding complaints, confrontation naming, semantic fluency, phonemic fluency and word-knowledge were evaluated.

Results: Complaints about forgetting the names of objects appeared in early tau stages (Braak 1-2), followed by naming difficulties (Braak 3-4), and widespread language impairments in later stages (Braak 5-6). Across the biologically-defined AD continuum, lower language performance was associated with tau accumulation predominantly in left-temporal language regions. In CU, only subjective word-finding complaints related to tau, indicating language concerns could reflect underlying pathology before measurable cognitive decline.

Discussion: Language measures support early detection and staging of AD pathophysiology and contribute to better align cognitive assessment with biological definitions of the disease.

Introduction: Inflammatory factors, particularly interleukin (IL)-6, are implicated in post-stroke cognitive decline, yet the association with longitudinal changes in these markers remains unclear.

Methods: Plasma IL-6 and other inflammatory markers were measured within 96 hours of ischemic stroke, and at 6-9 and 18-21 months, alongside cognitive assessment. Associations between inflammatory factors and cognition were examined using adjusted regression models.

Results: A doubling of IL-6 between admission and 6-9 months was associated with cognitive impairment at 18-21 months (odds ratio [OR] = 8.16; 95% confidence interval [CI] 1.82-47.26; p = 0.01), while each one-unit IL-6 increase was linked to a 1.5-point decrease in memory Z-scores (β = -1.50; 95% CI -2.57-0.43; p = 0.007). Smokers showed persistently blunted IL-6 trajectories (p < 0.05) and downregulated Toll-like receptor signaling (p < 0.05). Exploratory analyses suggested that lower socioeconomic status may relate to 6-month IL-6 concentrations via smoking.

Discussion: Post-stroke IL-6 trajectories associate with later cognition, highlighting potential therapeutic targets.

Background: Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown.

Methods: In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months.

Results: Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences.

Conclusion: Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker.

Introduction: Cognitive impairment in hospitalized older adults without delirium is often undiagnosed. We evaluated the diagnostic accuracy and prognostic value of two brief bedside screening tools-the 10-point Cognitive Screener (10-CS) and Short Portable Mental Status Questionnaire (SPMSQ).

Methods: Multicenter prospective cohort of 2003 patients ≥65 years of age without delirium, admitted to 43 hospitals in five countries of the Creating a Hospital Assessment Network in Geriatrics (CHANGE) Study. Screening was completed within 48 h of admission. Dementia was defined as informant-based Clinical Dementia Rating ≥1.

Results: Dementia prevalence was 22%, with 35% undiagnosed. Both tools showed good accuracy for detecting dementia, with the 10-CS slightly more accurate than SPMSQ (area under the curve [AUC] = 0.87 vs 0.85; p = 0.02). After adjustment, cognitive impairment detected by either tool was associated with increased risk of incident delirium, hospital-associated disability in self-care activities, and 90-day mortality, but not prolonged stay.

Discussion: Brief bedside screening identified dementia and predicted adverse outcomes, supporting its integration into routine hospital care.

Introduction: Individuals with Down syndrome (DS) are at risk for Alzheimer's disease (AD). However, diagnosis remains challenging due to variability of intellectual ability and symptom presentation. To investigate whether serum AD biomarkers enhance accuracy of the German version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-G), we combined test scores with neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels.

Methods: Seventy-eight DS individuals (49% female) completed the DSQIID-G; previous cohort data were added for a pooled sample (n = 164, 47% female). Serum NfL and GFAP were assessed using the automated microfluid Ella system.

Results: Combining the DSQIID-G with NfL or GFAP resulted in improved accuracy in every diagnostic subgroup. The Youden index in the pooled samples yielded a cut-off score at 6.5.

Discussion: The DSQIID-G is a robust screening tool and its combination with AD blood biomarkers aids earlier identification of individuals requiring further diagnostics for DS-associated AD.

Introduction: Inflammation contributes to Alzheimer's disease (AD), but its stage-specific and amyloid-dependent patterns remain unclear.

Methods: We analyzed 964 participants from the Bio-Hermes cohort (cognitively normal [CN] = 404, mild cognitive impairment [MCI] = 302, mild AD = 258). Plasma levels of 32 cytokines, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified alongside core AD biomarkers. Associations with cognition, amyloid, apolipoprotein E (APOE) ε4, and clinical outcomes were assessed using analysis of covariance, partial correlations, and regression models.

Results: Twenty-four cytokines, NfL, and GFAP differed across cognitive groups. Amyloid stratification revealed a core amyloid-independent profile (14 cytokines + NfL) and a broader amyloid-specific profile including GFAP, interleukin (IL)-1β, and IL-18, implicating microglial inflammasome and astrocytic activation. Stage-dependent patterns suggested inflammation may act as early driver, concurrent process, or late amplifier. Paradoxical associations (e.g., eotaxin-2, IL-2R with better memory) and APOE ε4-linked immune differences indicated context-dependent roles.

Discussion: This exploratory study reveals biologically plausible, inflammatory heterogeneity in AD and highlights plasma cytokine profiles as candidate biomarkers and therapeutic targets, warranting investigation.

Background: Most Alzheimer's disease (AD) cases show mixed pathology, with α-synuclein (αSyn) aggregates present in a substantial proportion. The cerebrospinal fluid (CSF) α-synuclein seed amplification assay (αS-SAA) enables in vivo detection of pathogenic αSyn aggregates, but its clinical significance remains unclear.

Methods: We prospectively evaluated 108 individuals with mild cognitive impairment or mild dementia due to suspected AD undergoing lumbar puncture for anti-amyloid therapy (ATT) eligibility. CSF AD biomarkers and αS-SAA were analyzed alongside cognitive, olfactory, and rapid eye movement sleep behavior disorder (RBD) assessments.

Results: Of 65 participants with biomarker-confirmed AD, 21 (32.3%) were αS-SAA positive. Positivity was linked to older age at testing and self-reported olfactory impairment (P = 0.004), but not other demographic or cognitive features. Within the αS-SAA-positive group, RBD presence correlated with faster seeding kinetics.

Conclusions: αS-SAA positivity is common in early AD and associated with olfactory dysfunction. Longitudinal follow-up is required to test if assay status predicts response to ATTs.

Introduction: The glymphatic system dysfunction is associated with cognitive decline in neurodegenerative diseases such as Alzheimer's disease (AD).

Methods: We introduce the G-Along Perivascular Space (G-ALPS) index, an optimized version of the ALPS index derived using Genetic Programming, and use it to analyze 217 diffusion tensor imaging (DTI) samples.

Results: Compared to the ALPS, the proposed G-ALPS index shows a stronger correlation with cognitive measures, including Mini-Mental State Examination (MMSE, 2.78% improvement), Clinical Dementia Rating (CDR, 5.13% improvement), and Functional Activities Questionnaire (FAQ, 10% improvement), as demonstrated by the analysis of fiber diffusivities in DTI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Furthermore, the G-ALPS exhibits enhanced sensitivity in identifying the effects of aging (94.81% improvement in AD individuals, 105% improvement in patients with mild cognitive impairment [MCI], and 81.25% improvement in normal controls) and sleep-related disorders (21.27% improvement in correlation with MMSE, and 2.53% improvement in correlation with Pittsburgh Sleep Quality Index [PSQI]) using the Human Connectome Project (HCP) dataset.

Discussion: Our results suggest that the G-ALPS index may be an indirect metric for assessing the glymphatic system's function or dysfunction.