دورية أكاديمية
أعرض في EDS

Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.

التفاصيل البيبلوغرافية
العنوان: Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.
المؤلفون: Morales CD; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Cotton-Samuel D; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Lao PJ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Chang JF; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Pyne JD; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Alshikho MJ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Lippert RV; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Bista K; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Hale C; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Edwards NC; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Igwe KC; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Deters K; Department of Integrative Biology & Physiology, University of California, Los Angeles, CA, USA., Zimmerman ME; Department of Psychology, Fordham University, Bronx, NY, USA., Brickman AM; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA. amb2139@columbia.edu.
المصدر: Alzheimer's research & therapy [Alzheimers Res Ther] 2024 Feb 02; Vol. 16 (1), pp. 25. Date of Electronic Publication: 2024 Feb 02.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101511643 Publication Model: Electronic Cited Medium: Internet ISSN: 1758-9193 (Electronic) NLM ISO Abbreviation: Alzheimers Res Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central Ltd.
مواضيع طبية MeSH: Alzheimer Disease*/complications , Alzheimer Disease*/diagnostic imaging , Cerebrovascular Disorders*/complications , Cerebrovascular Disorders*/diagnostic imaging , Cerebrovascular Disorders*/pathology , Cognitive Dysfunction*/pathology , White Matter*/pathology, Aged ; Female ; Humans ; Male ; Brain/pathology ; Cognition ; Magnetic Resonance Imaging ; Prospective Studies ; Clinical Trials as Topic
مستخلص: Background: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial.
Methods: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status.
Results: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status.
Conclusion: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.
(© 2024. The Author(s).)
References: Ann Neurol. 2016 Jun;79(6):929-39. (PMID: 27016429)
Neurobiol Aging. 2023 Feb;122:112-119. (PMID: 36543016)
Neurology. 2019 Jan 15;92(3):e253-e262. (PMID: 30568001)
JAMA. 2023 Aug 8;330(6):512-527. (PMID: 37459141)
N Engl J Med. 2023 Jan 5;388(1):9-21. (PMID: 36449413)
N Engl J Med. 2012 Aug 30;367(9):795-804. (PMID: 22784036)
Brain Commun. 2020 Aug 19;2(2):fcaa132. (PMID: 33215083)
Magn Reson Imaging. 2022 Jan;85:71-79. (PMID: 34662699)
Ann Neurol. 2020 Dec;88(6):1165-1177. (PMID: 32944999)
Alzheimers Dement. 2022 Mar;18(3):422-433. (PMID: 34322985)
Curr Opin Psychiatry. 2018 Mar;31(2):147-152. (PMID: 29232251)
Alzheimers Dement. 2018 Apr;14(4):535-562. (PMID: 29653606)
J Psychiatr Res. 1975 Nov;12(3):189-98. (PMID: 1202204)
Lancet Neurol. 2018 Jan;17(1):27. (PMID: 29263003)
Arch Neurol. 2012 Dec;69(12):1621-7. (PMID: 22945686)
Neurotox Res. 2010 Nov;18(3-4):339-46. (PMID: 20352396)
Mol Neurodegener. 2021 Jul 21;16(1):49. (PMID: 34289882)
BMJ. 2021 Feb 25;372:n156. (PMID: 33632704)
Sci Transl Med. 2014 Mar 19;6(228):228fs13. (PMID: 24648338)
Arch Neurol. 2008 Sep;65(9):1202-8. (PMID: 18779424)
N Engl J Med. 2023 Sep 21;389(12):1096-1107. (PMID: 37458272)
Brain. 2023 Nov 2;146(11):4414-4424. (PMID: 37280110)
Brain Sci. 2023 Jan 28;13(2):. (PMID: 36831761)
JAMA Neurol. 2023 Dec 1;80(12):1353-1363. (PMID: 37843849)
JAMA Neurol. 2014 Aug;71(8):961-70. (PMID: 24886908)
Alzheimers Dement. 2020 Jul;16(7):1078-1094. (PMID: 32627328)
Science. 1992 Apr 10;256(5054):184-5. (PMID: 1566067)
Lancet Neurol. 2013 Feb;12(2):207-16. (PMID: 23332364)
Brain Pathol. 2005 Jan;15(1):84-7. (PMID: 15779241)
Nat Rev Neurol. 2015 Mar;11(3):157-65. (PMID: 25686760)
Arch Neurol. 2008 Aug;65(8):1053-61. (PMID: 18695055)
Neurobiol Aging. 2015 Jan;36(1):27-32. (PMID: 25155654)
J Nucl Med. 2015 Nov;56(11):1736-41. (PMID: 26338898)
J Alzheimers Dis. 2023;94(2):497-507. (PMID: 37334596)
Alzheimers Dement. 2023 Aug;19(8):3738-3748. (PMID: 37027506)
Neurology. 2021 Mar 16;96(11):e1491-e1500. (PMID: 33568538)
Curr Alzheimer Res. 2015;12(7):632-9. (PMID: 26027808)
Brain. 2022 Dec 19;145(12):4489-4505. (PMID: 35762829)
Alzheimers Dement. 2023 Sep;19(9):4260-4261. (PMID: 37437028)
Acta Neuropathol. 2017 Aug;134(2):171-186. (PMID: 28488154)
Brain. 2012 Jul;135(Pt 7):2115-25. (PMID: 22556189)
JAMA Neurol. 2021 Nov 1;78(11):1305-1306. (PMID: 34605885)
Alzheimers Dement. 2021 Apr;17(4):696-701. (PMID: 33135381)
J Cereb Blood Flow Metab. 2021 May;41(5):1162-1174. (PMID: 32955960)
معلومات مُعتمدة: R25 NS117367 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Alzheimer’s disease; Amyloid; Clinical trial; White matter hyperintensities
تواريخ الأحداث: Date Created: 20240203 Date Completed: 20240212 Latest Revision: 20240517
رمز التحديث: 20240517
مُعرف محوري في PubMed: PMC10836014
DOI: 10.1186/s13195-024-01395-x
PMID: 38308344
قاعدة البيانات: MEDLINE
الوصف
تدمد:1758-9193
DOI:10.1186/s13195-024-01395-x