دورية أكاديمية
Synaptic density patterns in early Alzheimer's disease assessed by independent component analysis.
| العنوان: | Synaptic density patterns in early Alzheimer's disease assessed by independent component analysis. |
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| المؤلفون: | Fang XT; Yale PET Center, Yale University School of Medicine, New Haven, CT 06520, USA., Raval NR; Yale PET Center, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA., O'Dell RS; Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA., Naganawa M; Yale PET Center, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA., Mecca AP; Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA., Chen MK; Yale PET Center, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA., van Dyck CH; Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA., Carson RE; Yale PET Center, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA. |
| المصدر: | Brain communications [Brain Commun] 2024 Mar 26; Vol. 6 (2), pp. fcae107. Date of Electronic Publication: 2024 Mar 26 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101755125 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-1297 (Electronic) Linking ISSN: 26321297 NLM ISO Abbreviation: Brain Commun Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Oxford] : Oxford University Press, [2019]- |
| مستخلص: | Synaptic loss is a primary pathology in Alzheimer's disease and correlates best with cognitive impairment as found in post-mortem studies. Previously, we observed in vivo reductions of synaptic density with [ 11 C]UCB-J PET (radiotracer for synaptic vesicle protein 2A) throughout the neocortex and medial temporal brain regions in early Alzheimer's disease. In this study, we applied independent component analysis to synaptic vesicle protein 2A-PET data to identify brain networks associated with cognitive deficits in Alzheimer's disease in a blinded data-driven manner. [ 11 C]UCB-J binding to synaptic vesicle protein 2A was measured in 38 Alzheimer's disease (24 mild Alzheimer's disease dementia and 14 mild cognitive impairment) and 19 cognitively normal participants. [ 11 C]UCB-J distribution volume ratio values were calculated with a whole cerebellum reference region. Principal components analysis was first used to extract 18 independent components to which independent component analysis was then applied. Subject loading weights per pattern were compared between groups using Kruskal-Wallis tests. Spearman's rank correlations were used to assess relationships between loading weights and measures of cognitive and functional performance: Logical Memory II, Rey Auditory Verbal Learning Test-long delay, Clinical Dementia Rating sum of boxes and Mini-Mental State Examination. We observed significant differences in loading weights among cognitively normal, mild cognitive impairment and mild Alzheimer's disease dementia groups in 5 of the 18 independent components, as determined by Kruskal-Wallis tests. Only Patterns 1 and 2 demonstrated significant differences in group loading weights after correction for multiple comparisons. Excluding the cognitively normal group, we observed significant correlations between the loading weights for Pattern 1 (left temporal cortex and the cingulate gyrus) and Clinical Dementia Rating sum of boxes ( r = -0.54, P = 0.0019), Mini-Mental State Examination ( r = 0.48, P = 0.0055) and Logical Memory II score ( r = 0.44, P = 0.013). For Pattern 2 (temporal cortices), significant associations were demonstrated between its loading weights and Logical Memory II score ( r = 0.34, P = 0.0384). Following false discovery rate correction, only the relationship between the Pattern 1 loading weights with Clinical Dementia Rating sum of boxes ( r = -0.54, P = 0.0019) and Mini-Mental State Examination ( r = 0.48, P = 0.0055) remained statistically significant. We demonstrated that independent component analysis could define coherent spatial patterns of synaptic density. Furthermore, commonly used measures of cognitive performance correlated significantly with loading weights for two patterns within only the mild cognitive impairment/mild Alzheimer's disease dementia group. This study leverages data-centric approaches to augment the conventional region-of-interest-based methods, revealing distinct patterns that differentiate between mild cognitive impairment and mild Alzheimer's disease dementia, marking a significant advancement in the field. Competing Interests: The authors report no competing interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.) |
| References: | J Nucl Med. 2017 Aug;58(8):1314-1317. (PMID: 28254868) Hum Brain Mapp. 2009 Mar;30(3):711-24. (PMID: 18266214) Neural Comput. 1995 Nov;7(6):1129-59. (PMID: 7584893) Eur J Nucl Med Mol Imaging. 2021 May;48(5):1327-1338. (PMID: 33416954) J Nucl Med. 2016 May;57(5):777-84. (PMID: 26848175) Acta Neurol Scand Suppl. 1996;165:3-12. (PMID: 8740983) Neurology. 1992 Jan;42(1):183-8. (PMID: 1734300) Front Hum Neurosci. 2010 Mar 08;4:10. (PMID: 20300463) Neurobiol Aging. 2006 Oct;27(10):1372-84. (PMID: 16289476) Alzheimers Dement. 2020 Jul;16(7):974-982. (PMID: 32400950) Alzheimers Dement. 2011 May;7(3):263-9. (PMID: 21514250) Nucl Med Biol. 2016 Jun;43(6):325-32. (PMID: 27260773) Neuroimage Clin. 2023;39:103457. (PMID: 37422964) Alzheimers Dement. 2018 Apr;14(4):535-562. (PMID: 29653606) J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52. (PMID: 12468889) Neurology. 2007 May 1;68(18):1501-8. (PMID: 17470753) Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):390-402. (PMID: 31468182) Neurosci Lett. 1994 Jun 6;174(1):67-72. (PMID: 7970158) Alzheimers Dement. 2011 May;7(3):270-9. (PMID: 21514249) Neurobiol Aging. 2000 Jan-Feb;21(1):19-26. (PMID: 10794844) Med Phys. 2013 Oct;40(10):102503. (PMID: 24089924) Insight J. 2006;2006:209. (PMID: 25364771) Brain Connect. 2012;2(5):275-83. (PMID: 23025619) J Alzheimers Dis. 2011;24(3):547-57. (PMID: 21297265) J Alzheimers Dis. 2015;43(3):1073-90. (PMID: 25147118) Eur J Nucl Med Mol Imaging. 2021 Oct;48(11):3522-3529. (PMID: 33839891) J Neurosci. 1994 Sep;14(9):5223-35. (PMID: 8083732) Alzheimers Dement. 2022 Dec;18(12):2527-2536. (PMID: 35174954) Ann Neurol. 1990 May;27(5):457-64. (PMID: 2360787) J Neurol Sci. 1987 Apr;78(2):151-64. (PMID: 3572454) ACS Chem Neurosci. 2020 Feb 19;11(4):592-603. (PMID: 31961649) Sci Transl Med. 2016 Jul 20;8(348):348ra96. (PMID: 27440727) Ann Neurol. 1993 Feb;33(2):190-9. (PMID: 8434881) Neuroscience. 1999;94(4):1279-90. (PMID: 10625067) Neuroimage. 2021 Aug 15;237:118167. (PMID: 34000404) Brain. 2016 Jan;139(Pt 1):115-26. (PMID: 26637488) JAMA Neurol. 2018 Oct 1;75(10):1215-1224. (PMID: 30014145) J Nucl Med. 2014 Aug;55(8):1336-41. (PMID: 24935992) |
| معلومات مُعتمدة: | RF1 AG057553 United States AG NIA NIH HHS; P50 AG047270 United States AG NIA NIH HHS; P30 AG021342 United States AG NIA NIH HHS; R01 AG052560 United States AG NIA NIH HHS; P30 AG066508 United States AG NIA NIH HHS; R01 AG062276 United States AG NIA NIH HHS; RF1 AG057784 United States AG NIA NIH HHS; UL1 TR000142 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: Alzheimer’s disease; PET; cognition; independent component analysis; synaptic density |
| تواريخ الأحداث: | Date Created: 20240411 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC11004947 |
| DOI: | 10.1093/braincomms/fcae107 |
| PMID: | 38601916 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2632-1297 |
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| DOI: | 10.1093/braincomms/fcae107 |