A Lightweight ScaleDense–Transformer Framework with Auxiliary Quantum-Inspired Bottleneck Module for Whole-Lifespan Brain Age Prediction

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Abstract
Background/Objectives: This study introduces Lightweight ScaleDense–Transformer (LST-Net), a design-driven framework for whole-lifespan brain age prediction, aiming to improve prediction accuracy while maintaining structural and biological plausibility. Methods: LST-Net utilizes a ScaleDense–Transformer architecture specifically engineered to mirror the dual-nature of brain aging: ScaleDense modules capture fine-grained local anatomical changes, while Transformers model global, network-level reorganizations. The framework was developed and evaluated using a modeling cohort of 22,271 subjects from 17 heterogeneous data sources, covering a 96-year lifespan. Additionally, an auxiliary quantum module (VQC) was incorporated within the latent bottleneck to facilitate nonlinear latent representation transformation and improve representation expressiveness. Performance was primarily assessed using Mean Absolute Error (MAE). Results: LST-Net achieved a competitive MAE of 2.71 years in brain age prediction, demonstrating stability across a wide lifespan (0–96 years) and varying data sources. Longitudinal assessments and test–retest analysis further confirmed the model’s high reproducibility, yielding an Intraclass Correlation Coefficient (ICC) of 0.994. Conclusions: The current findings establish LST-Net as a scalable tool for brain health monitoring and large-scale screenings.
Funding Information
  • National Natural Science Foundation of China (81971683)
  • National Natural Science Foundation of China (12572064)
  • Beijing Municipality Natural Science Foundation (L182010)

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