Aim: We aimed to investigate the influence of admission fibrinogen-to-albumin ratio (FAR) on 3-month outcomes after acute lacunar stroke. Materials & methods: Consecutive patients with acute lacuna...

Objective: To evaluate whether genotype-guided antiplatelet therapy reduces the rates of cardiovascular events and bleeding events in patients with acute coronary syndrome (ACS). Methods: We systematically searched Pubmed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) (searched in September 2018) for controlled studies evaluating genotype-guided antiplatelet therapy in ACS with percutaneous coronary intervention (PCI) or without PCI. The primary endpoint was a composite of death, myocardial infarction (MI), stroke, targeted vessel revascularization and/or major bleeding. Results: A total of five studies involving 2900 patients were included. Compared with the conventional group, the genotype-guided group had a decreased risk of primary composite outcomes (RR= 0.54; 95% CI: 0.41–0.72; I² = 30%), death (RR =0.54; 95% CI: 0.32–0.94; I² = 21%), MI (RR =0.52; 95% CI: 0.31–0.88; I² = 49%), targeted vessel revascularization (RR =0.59; 95% CI: 0.35–0.98; I² = 0%), but not for stroke (RR =0.53; 95% CI: 0.22–1.24; I² = 0%) and bleeding events (RR =0.80; 95% CI: 0.51–1.25; I² = 33%). Conclusions: Genotype-guided strategies could reduce the rates of cardiovascular events without increasing bleeding events compared with conventional treatment in ACS. Future multi-center genotype-based RCTs are required to confirm these findings.

Objective: We aimed to test whether region‐specific factors, including spatial expression patterns of the tau‐encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity‐based modeling of the spatial variability in tau‐PET deposition in the Alzheimer disease (AD) spectrum.Methods: We included 685 participants (395 amyloid‐positive participants within AD spectrum and 290 amyloid‐negative controls) with tau‐PET and amyloid‐PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, ¹⁸F‐AV‐1451‐A05, and BioFINDER‐1). Resting‐state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain‐parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)‐to‐ROI functional connectivity, ROI‐level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid‐PET as predictors of group‐averaged and individual tau‐PET ROI values in amyloid‐positive participants.Results: Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau‐PET ROI values averaged across amyloid‐positive participants. Stepwise addition of MAPT gene expression and amyloid‐PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient‐level tau‐PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R² range across studies = 0.118–0.148, 0.156–0.196, and 0.251–0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively).Interpretation: Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD. ANN NEUROL 2024;95:274–287

Background: It is unclear whether miR-491-5p, miR-206, miR-21-5p or miR-3123 are associated with functional outcomes and hemorrhagic transformation (HT) after acute ischemic stroke (AIS). In this study, we aimed to investigate the correlation between these four microRNAs and functional outcomes, as well as spontaneous HT after AIS; Methods: We included 215 AIS patients and retrospectively assayed for miR-21-5p, miR-206, miR-3123 and miR-491-5p levels in serum. Poor functional outcome was defined as a modified Rankin Scale score ≥ 3. Spontaneous HT referred to hemorrhage detected in follow-up brain imaging but not on admission, without reperfusion therapies. Logistic regression, generalized additive model and 2-piecewise regression model were used to explore the independent, non-linear correlation between miRNA expression levels and outcomes; Results: We included 215 AIS patients. Higher miR-491-5p level independently reduced the risk of poor functional outcomes at 1 year (OR 0.90, 95% CI 0.82–0.98, corrected p value = 0.044). Higher miR-206 level significantly increased the risk of spontaneous HT (OR 1.64, 95% CI 1.17–2.30, corrected p value = 0.016). There was a nonlinear correlation found between miR-491-5p level and 1 year outcome with an inflection point of 2.180, while an approximately linear correlation was observed with an inflection point of 2.037 between miR-206 level and spontaneous HT; Conclusions: Higher serum miR-491-5p level independently reduced risk of 1-year poor functional outcome of AIS patients. Higher serum miR-206 level independently increased the risk of spontaneous HT in AIS patients. These two miRNAs may be as the potential biomarkers for improving prognosis after AIS.

Hippocampal atrophy is a key marker of Alzheimer's disease (AD)- related neurodegeneration; however, hippocampal volume alone may not fully capture heterogeneity in cognitive decline. Left-right hippocampal asymmetry may provide complementary information, but its prognostic value for long-term cognitive decline, particularly in relation to AD pathology, remains unclear. To determine whether hippocampal total volume and left-right hippocampal asymmetry provide complementary and independent information in capturing cognitive decline and clinical progression, and to examine their relationship to AD pathology. Analysis of baseline MRI and longitudinal cognitive data over 10 years in four domains of memory, language, executive, and visuospatial function, using harmonized cognitive data from the Alzheimer's Disease Sequencing Project - Phenotype Harmonization Consortium (ADSP-PHC). Participants from ADNI 1, ADNI GO, ADNI 2, and ADNI 3 PARTICIPANTS: A total of 1,142 dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available baseline structural MRI, cerebrospinal fluid (CSF) amyloid-β (Aβ42) and phosphorylated tau (p-tau-181), and longitudinal cognitive follow-up. Total hippocampal volume (left + right) and hemispheric asymmetry (absolute left-right volumetric difference) were modeled simultaneously. Linear mixed-effects models examined associations with baseline performance and longitudinal change across four cognitive domains. Cox proportional hazards models assessed risk of clinical progression to clinical dementia over up to 10 years of follow-up (median follow-up 4 years; median 5 visits per participant). All analyses adjusted for age, sex, education, APOE ε4 status, and CSF biomarkers, with stratification by amyloid status. The study cohort included 546 women (47.8%), with a mean age of 72.54 ± 6.98 years. Smaller total hippocampal volume was consistently associated with worse baseline performance and faster decline across all four cognitive domains, even after adjustment for amyloid and tau. In contrast, greater left-right hippocampal asymmetry was selectively associated with worse performance and faster decline in memory, independent of total hippocampal volume. In amyloid-stratified analyses, total hippocampal volume showed broad associations with cognitive performance across multiple domains in both amyloid-positive and amyloid-negative participants, whereas hippocampal left-right asymmetry demonstrated selective associations with memory performance, which were observed only among amyloid-negative individuals. With respect to clinical progression to dementia, smaller total hippocampal volume was associated with a higher risk of progression in the overall cohort and within both amyloid groups. In contrast, hippocampal asymmetry was associated with progression risk only among amyloid-negative individuals (hazard ratio per SD increase = 1.31, 95% CI: 1.03-1.65). Hippocampal total volume and asymmetry capture distinct aspects of neurodegeneration, with asymmetry providing additional prognostic information for memory decline and clinical progression in the absence of detectable amyloid pathology.

INTRODUCTION: APOE genotype shows well-established dose-dependent associations with higher amyloid in cognitively unimpaired (CU) adults. In contrast, associations with tau burden and cognition are less well characterized. METHODS: We performed a cross-sectional analysis of harmonized multi-cohort ADSP-PHC data from 4,380 CU participants across 4 cohorts with APOE genotype, amyloid PET, and cognitive data from four domains of memory, language, executive, and visuospatial function, including a subset of 758 with tau PET imaging. RESULTS: APOE ε4 showed a strong dose-dependent association with amyloid burden and amyloid positivity, with the highest levels observed among ε4 homozygotes. Associations between APOE and global tau burden were more modest and appeared to be driven mainly by ε4 homozygotes, while regional analyses showed localized APOE ε4-related associations in medial temporal regions. Independently, higher tau burden was associated with lower memory and language performance. CONCLUSIONS: In CU older adults, APOE ε4 was most strongly associated with amyloid burden, with more modest associations observed for medial temporal tau burden. Highlights: APOE ε4 showed dose-dependent associations with amyloid burden and age-related amyloid differences APOE-related global tau associations were modest, mainly in ε44 group, with stronger medial temporal effects among ε4 carriers Higher tau burden was associated with lower memory and language performance, regardless APOE status RESEARCH IN CONTEXT: Systematic review: The authors reviewed the literature using PubMed and Google Scholar to examine relationships among APOE genotype, amyloid pathology, tau pathology, and cognition in cognitively unimpaired individuals. Previous studies from A4, ADNI, A4/LEARN, and large multicohort tau PET datasets have consistently shown strong APOE-related effects on amyloid burden and more modest regional effects on tau. The present study extends this literature using a large harmonized ADSP-PHC dataset with amyloid PET, tau PET, and harmonized cognitive measures. Interpretation: The findings suggest that amyloid abnormalities remain the main pathological feature linked to APOE genotype in cognitively unimpaired individuals. APOE-related effects on tau were smaller and were concentrated mainly in medial temporal regions. APOE genotype was not consistently related to cognition, while higher tau burden was associated with lower memory and language performance. Future directions: These findings support the use of APOE genotype as a stratification factor in studies of cognitively unimpaired individuals. Longitudinal studies will be important to clarify how APOE-related differences in amyloid and regional tau burden evolve over time and whether they are linked to later cognitive decline and progression to Alzheimer’s disease.