{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:57:32Z","timestamp":1790675852210,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emerging evidence suggests that extracranial tissues and immune-glymphatic interactions may contribute to neurodegenerative processes in Alzheimer's disease (AD). In this context, neuroimaging studies typically focus on intracranial brain structures, often excluding extracranial structures and adjacent meningeal regions through preprocessing steps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether full-head MRI contains potentially relevant information beyond the brain and whether explainable deep learning can identify spatial patterns associated with AD, mild cognitive impairment (MCI), and cognitively normal (CN) subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An explainable full-head 3D deep learning framework based on DenseNet-121 with transfer learning from MedicalNet was proposed and applied to T1 MP-RAGE MRI data from the ADNI dataset. The model was trained on full-head MRI volumes without skull stripping using subject-level splits and evaluated across clinically relevant classification scenarios. Grad-CAM was used to localize regions contributing to model predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the three-class task (AD, CN, MCI), the model achieved 75.00% accuracy and 86.09% ROC-AUC. Performance was highest for distinguishing AD from CN (91.07% accuracy, 95.16% ROC-AUC) and remained strong for the combined (AD\u2009+\u2009MCI) versus CN (85.58% accuracy, 96.17% ROC-AUC). Explainability analysis revealed consistent saliency patterns not only within intracranial regions but also in peripheral regions, which may correspond to extracranial structures, such as scalp and skull.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Full-head MRI may contain complementary, potentially diagnostically relevant information beyond the brain. Peripheral saliency patterns identified by our framework suggest a broader anatomical context for signals associated with AD. These findings are hypothesis-generating and require further validation across independent datasets and clinical studies, motivating targeted investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261478312","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:03:35Z","timestamp":1787238215000},"page":"1478-1492","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Explainable 3D deep learning from full-head MRI suggests scalp and skull involvement in Alzheimer's disease"],"prefix":"10.1177","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4218-8913","authenticated-orcid":false,"given":"Mona","family":"Ebadi Jalal","sequence":"first","affiliation":[{"name":"University of Louisville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-8335","authenticated-orcid":false,"given":"Ramin","family":"Hamidi","sequence":"additional","affiliation":[{"name":"University of Louisville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3794-4704","authenticated-orcid":false,"given":"Bryan","family":"Harris","sequence":"additional","affiliation":[{"name":"University of Louisville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5274-8596","authenticated-orcid":false,"given":"Adel","family":"Elmaghraby","sequence":"additional","affiliation":[{"name":"University of Louisville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5721-1843","authenticated-orcid":false,"given":"Robert P.","family":"Friedland","sequence":"additional","affiliation":[{"name":"University of Louisville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Is it time to approve drugs based on amyloid removal? Alzforum https:\/\/www.alzforum.org\/news\/research-news\/it-time-approve-drugs-based-amyloid-removal (2024 accessed 25 April 2026)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01883-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2025.106217"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.seminoncol.2025.152398"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006654"},{"key":"e_1_3_3_8_2","article-title":"Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration","volume":"118","author":"Wang C","year":"2021","unstructured":"Wang C, Lau CY, Ma F, et al. Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration. Proc Natl Acad Sci U S A 2021; 118: e2106504118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-026-01005-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1661-y"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107988"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jimmun\/vkaf267"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.09.017"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.11.006"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.5826\/dpc.1501a4921"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.37897\/RJN.2024.4.2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1880010509"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.03.004"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.871706"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/s22082911"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0302358"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1142\/S0129065722500538"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-05568-y"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01681-w"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1109\/TNSRE.2023.3337533"},{"key":"e_1_3_3_26_2","unstructured":"Cardoso MJ Li W Brown R et al. MONAI: An open-source framework for deep learning in healthcare. arXiv 2022; DOI: 10.48550\/ARXIV.2211.02701."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2016.03.001"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2020.101694"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1109\/CVPR.2017.243"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-85277-8"},{"key":"e_1_3_3_31_2","unstructured":"Chen S Ma K Zheng Y. Med3D: transfer learning for 3D medical image analysis. arXiv 2019; DOI: 10.48550\/arXiv.1904.00625."},{"key":"e_1_3_3_32_2","first-page":"618","volume-title":"Grad-CAM: visual explanations from deep networks via gradient-based localization","author":"Selvaraju RR","unstructured":"Selvaraju RR, Cogswell M, Das A, et al. Grad-CAM: visual explanations from deep networks via gradient-based localization. In: 2017 IEEE International Conference on Computer Vision (ICCV), Venice: IEEE, pp.618\u2013626."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2023.110786"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.143.1.7063747"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12791"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142841"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202510109"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007978"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113024"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00231"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00960-5"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh3884"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp9563"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2024.10.014"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71201"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X261419964"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12808"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-72762-5"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001340000792"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-025-01074-0"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/psyrad\/kkag012"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-025-02299-6"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24135"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(85)90543-9"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-12994-5"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00194-2"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-171088"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2024.137702"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.107134"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-026-13651-1"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-70099-7"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1109\/ACCESS.2025.3556569"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261478312","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261478312","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261478312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:08:29Z","timestamp":1790672909000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261478312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1177\/13872877261478312"],"URL":"https:\/\/doi.org\/10.1177\/13872877261478312","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}