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image of Multimodal Deep Learning Approaches for Early Detection of Alzheimer’s Disease: A Comprehensive Systematic Review of Image Processing Techniques

Abstract

Introduction

Alzheimer's disease (AD) is the most common form of dementia, and it is important to diagnose the disease at an early stage to help people with the condition and their families. Recently, artificial intelligence, especially deep learning approaches applied to medical imaging, has shown potential in enhancing AD diagnosis. This comprehensive review investigates the current state of the art in multimodal deep learning for the early diagnosis of Alzheimer's disease using image processing.

Methods

The research underpinning this review spanned several months. Numerous deep learning architectures are examined, including CNNs, transfer learning methods, and combined models that use different imaging modalities, such as structural MRI, functional MRI, and amyloid PET. The latest work on explainable AI (XAI) is also reviewed to improve the understandability of the models and identify the particular regions of the brain related to AD pathology.

Results

The results indicate that multimodal approaches generally outperform single-modality methods, and three-dimensional (volumetric) data provides a better form of representation compared to two-dimensional images.

Discussion

Current challenges are also discussed, including insufficient and/or poorly prepared datasets, computational expense, and the lack of integration with clinical practice. The findings highlight the potential of applying deep learning approaches for early AD diagnosis and for directing future research pathways.

Conclusion

The integration of multimodal imaging with deep learning techniques presents an exciting direction for developing improved AD diagnostic tools. However, significant challenges remain in achieving accurate, reliable, and understandable clinical applications.

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2025-08-07
2025-09-11
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References

  1. Knopman D.S. Amieva H. Petersen R.C. Chételat G. Holtzman D.M. Hyman B.T. Nixon R.A. Jones D.T. Alzheimer disease. Nat Rev Dis Primers 2021 7 1 33 10.1038/s41572‑021‑00269‑y 33986301
    [Google Scholar]
  2. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement 2023 19 4 1598 1695 10.1002/alz.13016 36918389
    [Google Scholar]
  3. Behl T. Kaur I. Sehgal A. Khandige P.S. Imran M. Gulati M. Khalid Anwer M. Elossaily G.M. Ali N. Wal P. Gasmi A. The link between Alzheimer’s disease and stroke: A detrimental synergism. Ageing Res Rev 2024 99 102388 10.1016/j.arr.2024.102388 38914265
    [Google Scholar]
  4. Sinha S. Wal P. Goudanavar P. Divya S. Kimothi V. Jyothi D. Research on Alzheimer's disease (AD) involving the use of in vivo and in vitro models and mechanisms. CNS Agents Med Chem 2025 25 2 123 142 10.2174/0118715249293642240522054929 38803173
    [Google Scholar]
  5. Singh M. Agarwal V. Pancham P. Jindal D. Agarwal S. Rai S. Singh S. Gupta V. A comprehensive review and androgen deprivation therapy and its impact on Alzheimer’s disease risk in older men with prostate cancer. Degener Neurol Neuromuscul Dis 2024 14 33 46 10.2147/DNND.S445130 38774717
    [Google Scholar]
  6. Qiu S. Joshi P.S. Miller M.I. Xue C. Zhou X. Karjadi C. Chang G.H. Joshi A.S. Dwyer B. Zhu S. Kaku M. Zhou Y. Alderazi Y.J. Swaminathan A. Kedar S. Saint-Hilaire M.H. Auerbach S.H. Yuan J. Sartor E.A. Au R. Kolachalama V.B. Development and validation of an interpretable deep learning framework for Alzheimer’s disease classification. Brain 2020 143 6 1920 1933 10.1093/brain/awaa137 32357201
    [Google Scholar]
  7. Spasov S. Passamonti L. Duggento A. Liò P. Toschi N. A parameter-efficient deep learning approach to predict conversion from mild cognitive impairment to Alzheimer’s disease. Neuroimage 2019 189 276 287 10.1016/j.neuroimage.2019.01.031 30654174
    [Google Scholar]
  8. Cui R. Liu M. Hippocampus analysis by combination of 3-d densenet and shapes for Alzheimer’s disease diagnosis. IEEE J Biomed Health Inform 2019 23 5 2099 2107 10.1109/JBHI.2018.2882392 30475734
    [Google Scholar]
  9. Ebrahimighahnavieh M.A. Luo S. Chiong R. Deep learning to detect Alzheimer’s disease from neuroimaging: A systematic literature review. Comput Methods Programs Biomed 2020 187 105242 10.1016/j.cmpb.2019.105242 31837630
    [Google Scholar]
  10. Wen J. Thibeau-Sutre E. Diaz-Melo M. Samper-González J. Routier A. Bottani S. Dormont D. Durrleman S. Burgos N. Colliot O. Convolutional neural networks for classification of Alzheimer’s disease: Overview and reproducible evaluation. Med Image Anal 2020 63 101694 10.1016/j.media.2020.101694 32417716
    [Google Scholar]
  11. Helaly H.A. Badawy M. Hossny E. Deep learning approaches for Alzheimer’s disease detection from brain MRI: A comprehensive review. Neural Comput Appl 2024 36 1 1 25 10.1007/s00521‑023‑08697‑5
    [Google Scholar]
  12. Ramzan F. Khan M.U.G. Rehmat A. Iqbal S. Saba T. Rehman A. Mehmood Z. A deep learning approach for automated diagnosis and multi-class classification of Alzheimer’s disease stages using resting-state FMRI and residual neural networks. J Med Syst 2020 44 2 37 10.1007/s10916‑019‑1475‑2 31853655
    [Google Scholar]
  13. Noor M.B.T. Zenia N.Z. Kaiser M.S. Mamun S.A. Mahmud M. Application of deep learning in detecting neurological disorders from magnetic resonance images: A survey on the detection of Alzheimer’s disease, Parkinson’s disease and schizophrenia. Brain Inform 2020 7 1 11 10.1186/s40708‑020‑00112‑2 33034769
    [Google Scholar]
  14. Shen T. Jiang J. Lu J. Wang M. Zuo C. Yu Z. Yan Z. Predicting alzheimer disease from mild cognitive impairment with a deep belief network based on 18F-FDG-PET images. Mol Imaging 2019 18 1536012119877285 10.1177/1536012119877285 31552787
    [Google Scholar]
  15. Feng C. Elazab A. Yang P. Wang T. Zhou F. Hu H. Xiao X. Lei B. Deep learning framework for Alzheimer’s disease diagnosis via 3D-CNN and FSBi-LSTM. IEEE Access 2019 7 63605 63618 10.1109/ACCESS.2019.2913847
    [Google Scholar]
  16. Punjabi A. Martersteck A. Wang Y. Parrish T.B. Katsaggelos A.K. Neuroimaging modality fusion in Alzheimer’s classification using convolutional neural networks. PLoS One 2019 14 12 0225759 10.1371/journal.pone.0225759 31805160
    [Google Scholar]
  17. Ansart M. Epelbaum S. Bassignana G. Bône A. Bottani S. Cattai T. Couronné R. Faouzi J. Koval I. Louis M. Thibeau- Sutre E. Wen J. Wild A. Burgos N. Dormont D. Colliot O. Durrleman S. Predicting the progression of mild cognitive impairment using machine learning: A systematic, quantitative and critical review. Med Image Anal 2021 67 101848 10.1016/j.media.2020.101848 33091740
    [Google Scholar]
  18. Abuhmed T. El-Sappagh S. Alonso J.M. Robust hybrid deep learning models for Alzheimer’s progression detection. Knowl Base Syst 2021 213 106688 10.1016/j.knosys.2020.106688
    [Google Scholar]
  19. Rieke J. Eitel F. Weygandt M. Haynes J.D. Ritter K. Visualizing convolutional networks for mri-based diagnosis of Alzheimer’s disease. Understanding and Interpreting Machine Learning in Medical Image Computing Applications Cham Springer 2018 24 31 10.1007/978‑3‑030‑02628‑8_3
    [Google Scholar]
  20. Böhle M. Eitel F. Weygandt M. Ritter K. Layer-wise relevance propagation for explaining deep neural network decisions in MRI-based Alzheimer’s disease classification. Front Aging Neurosci 2019 11 194 10.3389/fnagi.2019.00194 31417397
    [Google Scholar]
  21. Rudin C. Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead. Nat Mach Intell 2019 1 5 206 215 10.1038/s42256‑019‑0048‑x 35603010
    [Google Scholar]
  22. Mamalakis A. Investigating the fidelity of explainable artificial intelligence methods for weather and climate applications. Artif Intell Earth Sys 2022 1 4 220012 10.1175/AIES‑D‑22‑0012.1
    [Google Scholar]
  23. Yang W. Survey on explainable AI: From approaches, limitations, opportunities to metrics, recent advances and challenges. CAAI Artif Intell Res 2023 2 19 10.1007/s44230‑023‑00038‑y
    [Google Scholar]
  24. Kindermans P.J. The (un)reliability of saliency methods. Explainable AI: Interpreting, Explaining and Visualizing Deep Learning Cham Springer 2019 267 280 10.1007/978‑3‑030‑28954‑6_10
    [Google Scholar]
  25. Jacovi A. Formalizing trust in artificial intelligence: Prerequisites, causes and goals of human trust in AI. 2021, pp. 624-635. Proceedings of the 2021 ACM Conference on Fairness, Accountability, and Transparency (FAccT ’21) 10.1145/3442188.3445923
    [Google Scholar]
  26. Poursabzi-Sangdeh F. Manipulating and Measuring Model Interpretability. 2021, pp. (1-52). Proceedings of the 2021 CHI Conference on Human Factors in Computing Systems (CHI ’21) 10.1145/3411764.3445315
    [Google Scholar]
  27. Hoffmann F. Bridging the Gap in XAI—the need for reliable metrics and robust evaluation strategies. arXiv:250204695 2025 1 5
    [Google Scholar]
  28. Velmurugan M. Developing guidelines for functionally-grounded evaluation of explainable AI. Knowl Base Syst 2025 299 112069 10.1016/j.knosys.2024.112069
    [Google Scholar]
  29. Khvostikov A. Aderghal K. Benois-Pineau J. Krylov A. 3D CNN-based classification using sMRI and MD-DTI images for Alzheimer’s disease studies. arXiv:180105968 2018 1 7 10.48550/arXiv.1801.05968
    [Google Scholar]
  30. Payan A. Montana G. Predicting Alzheimer’s disease: A neuroimaging study with 3D convolutional neural networks. 2015, pp. 1-5. IEEE International Conference on Image Processing 10.1109/ICIP.2015.7351000
    [Google Scholar]
  31. Hosseini-Asl E. Keynton R. El-Baz A. Alzheimer’s disease diagnostics by adaptation of 3D convolutional network. 2016, pp. 126-130. IEEE International Conference on Image Processing 10.1109/ICIP.2016.7532332
    [Google Scholar]
  32. Chen A.A. Luo C. Chen Y. Shinohara R.T. Shou H. Privacy-preserving harmonization via distributed ComBat. Neuroimage 2022 248 118822 10.1016/j.neuroimage.2021.118822 34958950
    [Google Scholar]
  33. Zhou X. Qiu S. Joshi P.S. Xue C. Killiany R.J. Mian A.Z. Chin S.P. Au R. Kolachalama V.B. Enhancing magnetic resonance imaging-driven Alzheimer’s disease classification performance using generative adversarial learning. Alzheimers Res Ther 2021 13 1 60 10.1186/s13195‑021‑00797‑5 33766132
    [Google Scholar]
  34. Mitrovska A. Safari P. Ritter K. Shariati B. Fischer J.K. Secure federated learning for Alzheimer’s disease detection. Front Aging Neurosci 2024 16 1324032 10.3389/fnagi.2024.1324032 38515517
    [Google Scholar]
  35. Marinescu RV Oxtoby NP Young AL Tadpole challenge: Prediction of longitudinal evolution in Alzheimer’s disease. arXiv2018:180503909 2018 1 6
    [Google Scholar]
  36. Ji Y. Zhu L. Yang Z. Improved Alzheimer’s disease diagnosis using ensemble learning with convolutional neural networks and structural MRI. Front Aging Neurosci 2023 15 1173265 10.3389/fnagi.2023.1173265
    [Google Scholar]
  37. Prajapati C. Rai S.N. Singh A.K. Chopade B.A. Singh Y. Singh S.K. Haque S. Prieto M.A. Ashraf G.M. An update of fungal endophyte diversity and strategies for augmenting therapeutic potential of their potent metabolites: Recent advancement. Appl Biochem Biotechnol 2025 197 5 2799 2866 10.1007/s12010‑024‑05098‑9 39907846
    [Google Scholar]
  38. Kang S.K. Seo S. Shin S.A. Deep learning for Alzheimer’s disease: A systematic review of structural and functional brain imaging. Diagnostics 2022 12 5 1075 10.3390/diagnostics12051075 35626231
    [Google Scholar]
  39. Samper-González J. Burgos N. Bottani S. Fontanella S. Lu P. Marcoux A. Routier A. Guillon J. Bacci M. Wen J. Bertrand A. Bertin H. Habert M.O. Durrleman S. Evgeniou T. Colliot O. Reproducible evaluation of classification methods in Alzheimer’s disease: Framework and application to MRI and PET data. Neuroimage 2018 183 504 521 10.1016/j.neuroimage.2018.08.042 30130647
    [Google Scholar]
  40. Farooq A. Anwar S. Awais M. Rehman S. A deep CNN based multi-class classification of Alzheimer’s disease using MRI. 2017, pp. 1-6. IEEE International Conference on Imaging Systems and Techniques 10.1109/IST.2017.8261460
    [Google Scholar]
  41. Zhang D. Wang Y. Zhou L. Yuan H. Shen D. Multimodal classification of Alzheimer’s disease and mild cognitive impairment. Neuroimage 2011 55 3 856 867 10.1016/j.neuroimage.2011.01.008 21236349
    [Google Scholar]
  42. Abd El-Latif A.A. Chelloug S.A. Alabdulhafith M. Hammad M. Accurate detection of Alzheimer’s disease using lightweight deep learning model on MRI data. Diagnostics 2023 13 7 1216
    [Google Scholar]
  43. Zhou T. Thung K.H. Zhu X. Shen D. Effective feature learning and fusion of multimodality data using stage‐wise deep neural network for dementia diagnosis. Hum Brain Mapp 2019 40 3 1001 1016 10.1002/hbm.24428 30381863
    [Google Scholar]
  44. Liu S. Yadav C. Fernandez-Granda C. Razavian N. On the design of convolutional neural networks for automatic detection of Alzheimer’s disease. Machine Learn. Med. Imag. 2020 11861 287 296 10.1007/978‑3‑030‑32692‑0_3
    [Google Scholar]
  45. Yadav A. Singh N. Singh A. Ashish A. Singh S. Rai S. Singh S. Singh R. Investigation of serum pro-inflammatory markers and trace elements among short stature in eastern uttar pradesh and bihar populations. J Inflamm Res 2024 17 6063 6073 10.2147/JIR.S473895 39253565
    [Google Scholar]
  46. Tripathi P. Lodhi A. Rai S. Nandi N. Dumoga S. Yadav P. Tiwari A. Singh S. El-Shorbagi A.N. Chaudhary S. Review of pharmacotherapeutic targets in Alzheimer’s disease and its management using traditional medicinal plants. Degener Neurol Neuromuscul Dis 2024 14 47 74 10.2147/DNND.S452009 38784601
    [Google Scholar]
  47. Altay O. Ulas C. Kara E. Guler E. Altay E.E. Attention-based recurrent neural networks for Alzheimer’s disease detection using structural MRI. Comput Biol Med 2023 158 106887 10.1016/j.compbiomed.2023.106887
    [Google Scholar]
  48. Ramakrishna K. Nalla L.V. Naresh D. Venkateswarlu K. Viswanadh M.K. Nalluri B.N. Chakravarthy G. Duguluri S. Singh P. Rai S.N. Kumar A. Singh V. Singh S.K. WNT-β catenin signaling as a potential therapeutic target for neurodegenerative diseases: Current status and future perspective. Diseases 2023 11 3 89 10.3390/diseases11030089 37489441
    [Google Scholar]
  49. Tripathi P.N. Srivastava P. Sharma P. Tripathi M.K. Seth A. Tripathi A. Rai S.N. Singh S.P. Shrivastava S.K. Biphenyl-3-oxo-1,2,4-triazine linked piperazine derivatives as potential cholinesterase inhibitors with anti-oxidant property to improve the learning and memory. Bioorg Chem 2019 85 82 96 10.1016/j.bioorg.2018.12.017 30605887
    [Google Scholar]
  50. Srivastava P. Tripathi P.N. Sharma P. Rai S.N. Singh S.P. Srivastava R.K. Shankar S. Shrivastava S.K. Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory. Eur J Med Chem 2019 163 116 135 10.1016/j.ejmech.2018.11.049 30503937
    [Google Scholar]
  51. Venugopalan J. Tong L. Hassanzadeh H.R. Wang M.D. Multimodal deep learning models for early detection of Alzheimer’s disease stage. Sci Rep 2021 11 1 3254 10.1038/s41598‑020‑74399‑w 33547343
    [Google Scholar]
  52. Castellano G. Esposito A. Lella E. Montanaro G. Vessio G. Automated detection of Alzheimer’s disease: A multi-modal approach with 3D MRI and amyloid PET. Sci Rep 2024 14 1 5210 10.1038/s41598‑024‑56001‑9 38433282
    [Google Scholar]
  53. Chamakuri R. Janapana H. A systematic review on recent methods on deep learning for automatic detection of Alzheimer’s disease. Med Novel Technol Devices 2025 25 100343 10.1016/j.medntd.2024.100343
    [Google Scholar]
  54. Grande G. Valletta M. Rizzuto D. et al. Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community. Nat Med 2025 31 2027 2035 10.1038/s41591‑025‑03605‑x
    [Google Scholar]
  55. Sarraf S. Tofighi G. Classification of Alzheimer’s disease using fMRI data and deep learning convolutional neural networks. arXiv:160308631 2016 1 6 10.48550/arXiv.1603.08631
    [Google Scholar]
  56. Rai S.N. Singh C. Singh A. Singh M.P. Singh B.K. Mitochondrial dysfunction: A potential therapeutic target to treat alzheimer’s disease. Mol Neurobiol 2020 57 7 3075 3088 10.1007/s12035‑020‑01945‑y 32462551
    [Google Scholar]
  57. Li F. Tran L. Thung K.H. Ji S. Shen D. Li J. A robust deep model for improved classification of AD/MCI patients. IEEE J Biomed Health Inform 2019 23 4 1613 1623 10.1109/JBHI.2018.2879501 25955998
    [Google Scholar]
  58. Basaia S. Agosta F. Wagner L. Canu E. Magnani G. Santangelo R. Filippi M. Automated classification of Alzheimer’s disease and mild cognitive impairment using a single MRI and deep neural networks. Neuroimage Clin 2019 21 101645 10.1016/j.nicl.2018.101645 30584016
    [Google Scholar]
  59. Suk H.I. Lee S.W. Shen D. Deep sparse multi-task learning for feature selection in Alzheimer’s disease diagnosis. Brain Struct Funct 2017 222 7 3249 3264 10.1007/s00429‑017‑1459‑2 25993900
    [Google Scholar]
  60. Cui R. Liu M. RNN-based longitudinal analysis for diagnosis of Alzheimer’s disease. Comput Med Imaging Graph 2019 73 1 10 10.1016/j.compmedimag.2019.01.005 30763637
    [Google Scholar]
  61. Jung J. Essential properties and explanation effectiveness of explainable artificial intelligence in healthcare: A systematic review. Heliyon 2023 9 5 e16110 10.1016/j.heliyon.2023.e16110
    [Google Scholar]
  62. Rathore S. Habes M. Iftikhar M.A. Shacklett A. Davatzikos C. A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer’s disease and its prodromal stages. Neuroimage 2017 155 530 548 10.1016/j.neuroimage.2017.03.057 28414186
    [Google Scholar]
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