Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration

作者：Thomas D. Parker, Richard A. I. Bethlehem, Jakob Seidlitz, Simon R. White, Michael David, Magdalena Kolanko, Joshua D. Bernstock, Lena Dorfschmidt, Niall Bourke, Anastasia Gailly de Taurines, Jessica Hain, Martina Del Giovane, Neil Graham, Karl Zimmerman, Ethan J. F. Losty, Michael Schöll, Meera Srikrishna, Paresh Malhotra, Maneesh C. Patel, Gregory Scott, Aaron Alexander‐Bloch, Edward T. Bullmore, David Sharp, for the Alzheimer’s Disease Neuroimaging Initiative, for the Frontotemporal Lobar Degeneration Neuroimaging Initiative, Howard Rosen, Bradford C. Dickerson, Kimoko Domoto-Reilly, David S. Knopman, Bradley F. Boeve, Adam L. Boxer, John Kornak, Bruce L. Miller, William W. Seeley, Maria‐Luisa Gorno‐Tempini, Scott McGinnis, Maria Luisa Mandelli · 发表于：Alzheimer s Research & Therapy · 年份：2025 · DOI：10.1186/s13195-025-01872-x · 被引用次数：2 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Functional Brain Connectivity Studies、Dementia and Cognitive Impairment Research

BACKGROUND: Determining whether MRI brain scans demonstrate atrophy that is beyond "normal for age" is challenging. Automated measurements of structural metrics in individual brain regions have shown promise as biomarkers of neurodegeneration, yet widely available reference standards that aid interpretation at the individual level are lacking. Normative modelling, enabling standardized "brain charts", represents a significant step in addressing this challenge by generating individualized age- and sex- adjusted centile scores derived from large, aggregated datasets for MRI-derived quantitative metrics. METHODS: Using normative data from 56,173 participants across the life course, we have developed regional cortical thickness and amygdala/hippocampal volume brain charts (adjusted for total intracranial volume) that can be applied at the individual level. At the group level, we investigate whether regional centile scores relate to cognitive performance (mini-mental state examination) and discriminate individuals with neuropathological evidence of Alzheimer's disease (n = 351) from propensity-matched controls from the National Alzheimer's Coordinating Center (NACC) dataset. In addition, we explored the relationships between disease stage, cognition, regional tau deposition and regional centile scores in amyloid-β-PET-positive individuals with Alzheimer's disease dementia (n = 39) and mild cognitive impairment (n = 71) from the Alzheimer's Disease Neuroimaging Initiative-3 (ADNI-3...