Multimodal brain age prediction using machine learning: combining structural MRI and 5-HT2AR PET derived features

Abstract

To better assess the pathology of neurodegenerative disorders and the efficacy of neuroprotective interventions, it is necessary to develop biomarkers that can accurately capture age-related biological changes in the human brain. Brain serotonin 2A receptors (5-HT2AR) show a particularly profound age-related decline and are also reduced in neurodegenerative disorders, such as Alzheimers disease. This study investigates whether the decline in 5-HT2AR binding, measured in vivo using positron emission tomography (PET), can be used as a biomarker for brain aging. Specifically, we aim to 1) predict brain age using 5-HT2AR binding outcomes, 2) compare 5-HT2AR-based predictions of brain age to predictions based on gray matter (GM) volume, as determined with structural magnetic resonance imaging (MRI), and 3) investigate whether combining 5-HT2AR and GM volume data improves prediction. We used PET and MR images from 209 healthy individuals aged between 18 and 85 years (mean=38, std=18), and estimated 5-HT2AR binding and GM volume for 14 cortical and subcortical regions. Different machine learning algorithms were applied to predict chronological age based on 5-HT2AR binding, GM volume, and the combined measures. The mean absolute error (MAE) and a cross-validation approach were used for evaluation and model comparison. We find that both the cerebral 5-HT2AR binding (mean MAE=6.63 years, std=0.74 years) and GM volume (mean MAE=6.95 years, std=0.83 years) predict chronological age accurately. Combining the two measures improves the prediction further (mean MAE=5.54 years, std=0.68). In conclusion, 5-HT2AR binding measured using PET might be useful for improving the quantification of a biomarker for brain aging.