What question did this study set out to answer?

The study aims to evaluate cortical asymmetry in relation to Alzheimer’s disease progression.

December 23, 2025Brain Communications0 citationsOpen Access

Cortical asymmetry in autosomal dominant Alzheimer’s disease progression

APAgnès Pérez‐MillanUniversitat Oberta de Catalunya NFNeus FalgàsAlzheimer's Association BBBeatríz BoschBiomedical Research Networking Center on Neurodegenerative Diseases

Key Points

The study aims to evaluate cortical asymmetry in relation to Alzheimer’s disease progression.
Analyzed Cortical Asymmetry Index (CAI) in mutation carriers of Alzheimer’s disease.
Used MRI scans from cohorts including the Clinic Barcelona and DIAN-OBS.
Conducted cross-sectional and longitudinal analyses with adjustments for variables like age and sex.
CAI distinguished asymptomatic and symptomatic mutation carriers from healthy controls.
Higher CAI correlated with elevated levels of neurofilament light chain in plasma and cerebrospinal fluid.
Longitudinally, CAI increased over time in symptomatic mutation carriers.

Abstract

Abstract The Cortical Asymmetry Index (CAI) evaluates the cortical thickness asymmetry between hemispheres. We investigated CAI in asymptomatic (AMC) and symptomatic (SMC) mutation carriers of Autosomal Dominant Alzheimer’s Disease (ADAD) to explore the brain asymmetry within the Alzheimer’s disease (AD) 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 (DIAN-OBS) were used as an independent, confirmatory cohort. Cerebrospinal fluid (CSF) and plasma neurofilament light chain (NfL) levels were included when available. Cortical thickness was calculated using Freesurfer and CAI was calculated via an open-source pipeline. Cross-sectional analyses examined CAI differences based on clinical classification and APOE ε4 status, adjusting for age, sex, and estimated years from onset (EYO), while correlations were assessed with age, EYO, Mini-Mental State Examination (MMSE) scores, and NfL. Longitudinal CAI evolution was modeled using generalized additive models (GAM) in the DIAN-OBS cohort, incorporating age, sex, and the interaction between group and EYO. The CAI successfully distinguished AMC and SMC from healthy controls (CTR) in the Clinic Barcelona cohort and SMC from CTR in DIAN-OBS. Higher CAI in mutation carriers (AMC and SMC combined) and in SMC were associated with higher plasma NfL levels, a closer proximity to symptom onset, and lower MMSE in the Clinic Barcelona cohort. In the DIAN-OBS cohort, mutation carriers exhibited increased CAI compared to CTR and correlated with elevated NfL (plasma and CSF), lower MMSE, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant CAI differences between AMC and SMC. Longitudinally, CAI increased over time significantly in SMC. These findings underscore brain asymmetry as a potential biomarker for early AD progression in ADAD, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

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