Judged by your neighbors: A novel framework for personalized assessment of brain structural aging effects in diverse populations

Leenings, Ramona; Winter, Nils R ; Ernsting, Jan; Konowski, Maximilian; Holstein, Vincent; Meinert, Susanne; Spanagel, Jennifer; Barkhau, Carlotta; Fisch, Lukas; Goltermann, Janik ; Gerdes, Malte Frank; Grotegerd, Dominik; Leehr, Elisabeth Johanna; Peters, Annette ; Krist, Lilian; Willich, Stefan N.; Pischon, Tobias ; Völzke, Henry; Haubold, Johannes; Kauczor, Hans-Ulrich; Niendorf, Thoralf; Richter, Maike Frederike; Dannlowski, Udo; Berger, Klaus; Jiang, Xiaoyi; Cole, James ; Opel, Nils und Hahn, Tim (2025): Judged by your neighbors: A novel framework for personalized assessment of brain structural aging effects in diverse populations. medRxiv

Abstract

Despite their promise, current neuroimaging biomarkers often fail to capture the full spectrum of inter-individual variability in brain structure and aging effects. This limits their ability to detect subtle norm deviations and impacts their utility for personalized care. We introduce Nearest Neighbor Normativity (N3) , a novel framework designed to resolve the confound between natural diversity and subtle pathological patterns. It evaluates individual brain structures from several meaningful viewpoints, accommodates a variety of co-existing normative prototypes and accounts for individually varying progression rates of brain structural decline. Using MRI data of 36,896 individuals, we provide empirical evidence that the N3 biomarker effectively disentangles natural inter-individual variability from pathological alterations, significantly outperforming brain age models and traditional normative modeling approaches in the detection of neurodegenerative diseases. The N3 framework is easily adaptable to various medical domains, fostering individualized and context-rich biomarkers and paving the way for more targeted and personalized therapeutic strategies.

• Dokumententyp: Paper
• Keywords: Brain Age; Density-Estimation; Diversity; Normative Modeling; Precision Medicine
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch