👤 Neus Falgàs

The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and Show less

Progression in Alzheimer's disease (AD) involves three main interrelated biological axes-tau deposition, neurodegeneration, and neuroinflammation-that jointly drive cognitive decline. Although several cerebrospinal fluid (CSF) and plasma biomarkers along these axes are well validated for diagnosis, their value for prognosis remains uncertain. We assessed how baseline markers of each axis predict cognitive trajectories in biomarker-confirmed AD. We included 136 A + T + N + individuals (median follow-up = 24 months [IQR 12-24]; mean = 17.6 months [SD = 12.4]). Tau-deposition markers (CSF p-Tau181; plasma p-Tau181 and p-Tau217), neurodegeneration markers (CSF t-Tau; CSF and plasma neurofilament light chain, NfL) and a neuroinflammation marker (plasma glial fibrillary acidic protein, GFAP) were quantified using CLEIA, ELISA or Simoa, and stratified into tertiles. Participants were classified by age at onset, clinical phenotype, and APOE ε4 status. Cognition was assessed annually with a comprehensive neuropsychological battery. Linear mixed-effects models (MMRM) were used to test biomarker-cognition associations and interactions with clinical variables. Elevated CSF p-Tau181 and NfL levels were associated with greater decline in memory and executive function. Among plasma biomarkers, p-Tau217 and GFAP showed the strongest associations with widespread cognitive decline, particularly in language, visuospatial, and executive domains. These associations were independent of age at onset, clinical phenotype, and APOE ε4 status. Our findings highlight the potential prognostic value of fluid biomarkers in AD, especially CSF p-Tau181 and NfL, and plasma p-Tau217 and GFAP. These results suggest promise for improving disease monitoring, although prognostic utility at the individual level remains uncertain. Show less