Cortical tortuosity as a potential clinical biomarker for Alzheimer’s disease: A 3D MRI analysis of brain morphological changes

BACKGROUND: Alzheimer's disease (AD) is characterized by progressive brain morphological changes that are not fully captured by traditional volumetric measures. Cortical tortuosity, a novel measure of cortical folding complexity, provides complementary insights into these changes and has the potential to serve as a biomarker for AD. OBJECTIVE: To evaluate cortical tortuosity as a biomarker for brain morphological changes in AD, and to establish whether it provides independent information beyond cortical thickness and volume, in relation to disease severity and cognitive performance. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we analyzed 228 AD dementia patients, 620 individuals with mild cognitive impairment (MCI), and 506 healthy controls (CN). Cortical tortuosity was computed across multiple brain regions using a 3D slope chain code method. Statistical analyses adjusted for study site, ADNI phase, sex, age, regional brain volume, cortical thickness, and white matter hyperintensities (WMH) were conducted to assess group differences and correlations with cognitive performance. RESULTS: ) regions. Lower tortuosity in the left inferior temporal region was associated with higher Clinical Dementia Rating Scale-Sum of Boxes (CDRSB) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS) scores, indicating a link between reduced tortuosity and greater cognitive impairment. CONCLUSION: Cortical tortuosity provides a complementary measure of brain morphological changes in AD, with potential as a biomarker for disease progression and cognitive decline. These findings highlight the clinical utility of cortical tortuosity in understanding and monitoring AD-related brain changes.

Authors

• Maria-Julieta Mateos
• James J. Lah
• Deqiang Qiu

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