# Hybrid Classical-Quantum (HCQ) Alzheimer's Classification via Supervised β-VAE and Quantum Kernels

arXiv: https://arxiv.org/abs/2606.14194 · HTML: https://mlsanity.com/paper/2606.14194/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 25 references that are in the map.
- First posted on arXiv 12 Jun 2026.

## Builds on (most cited first, 12 of 12)

- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Supervised learning with quantum enhanced feature spaces](https://mlsanity.com/paper/1804.11326/) (2018)
- [Generalization in quantum machine learning from few training data](https://mlsanity.com/paper/2111.05292/) (2021)
- [Supervised quantum machine learning models are kernel methods](https://mlsanity.com/paper/2101.11020/) (2021)
- [Convolutional Neural Networks for Classification of Alzheimer's Disease: Overview and Reproducible Evaluation](https://mlsanity.com/paper/1904.07773/) (2019)
- [Exponential concentration in quantum kernel methods](https://mlsanity.com/paper/2208.11060/) (2022)
- [Training Quantum Embedding Kernels on Near-Term Quantum Computers](https://mlsanity.com/paper/2105.02276/) (2021)
- [Quantum Kernel Methods under Scrutiny: A Benchmarking Study](https://mlsanity.com/paper/2409.04406/) (2024)
- [CompressedMediQ: Hybrid Quantum Machine Learning Pipeline for High-Dimensional Neuroimaging Data](https://mlsanity.com/paper/2409.08584/) (2024)
- [Quantum AI for Alzheimer's disease early screening](https://mlsanity.com/paper/2405.00755/) (2024)
- [Attention-based 3D CNN with Multi-layer Features for Alzheimer's Disease Diagnosis using Brain Images](https://mlsanity.com/paper/2308.05655/) (2023)

## Abstract (arXiv)

This paper presents a two-stage Hybrid Classical-Quantum (HCQ) pipeline for binary Alzheimer's disease (AD) classification from 3D T1-weighted structural MRI volumes, where the classical and quantum components are designed to complement each other rather than operate independently. A supervised 3D β-variational autoencoder (VAE) is trained end-to-end under voxel-wise reconstruction, KL-divergence, and focal classification losses that compress each 3D MRI volume (resized from 152 x 184 x 152 to 96 x 96 x 96) into a 64-dimensional latent code. Partial Least Squares (PLS) regression selects the six components in the latent code that best separate Alzheimer's Disease (AD) from cognitively normal (CN) subjects and rescales them into rotation angles, which are encoded onto a six-qubit register using the ZZ quantum feature map to give us the respective quantum states. The input to a precomputed-kernel Support Vector Machine (SVM) is an N x N Gram matrix (N = 308), created by calculating the overlap between every pair of quantum states. The novelty of this work lies in the fact that the quantum kernel operates directly on disease-aware features that are learned end-to-end by a supervised autoencoder, rather than on pre-extracted inputs. On 308 ADNI-1 subjects, consisting of 137 AD and 171 CN subjects, the baseline achieved 67.2% accuracy and 0.759 AUC, while the stability-enhanced variant reached 72.1% accuracy and 0.799 AUC with cross-fold variance halved. 3D Grad-CAM further helped validate our model's focus on brain regions linked to Alzheimer's. The HCQ pipeline could serve as a general-purpose framework for diagnostic classification across biomedical imaging domains that present similar challenges for classical approaches.