Heterogeneity of factors associated with cognitive decline and cortical atrophy in early- versus late-onset Alzheimer's disease.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Alzheimer Disease*/pathology ; Alzheimer Disease*/diagnostic imaging ; Atrophy* ; Cognitive Dysfunction*/pathology ; Cognitive Dysfunction*/diagnostic imaging ; Cerebral Cortex*/pathology ; Cerebral Cortex*/diagnostic imaging ; Neuropsychological Tests* ; Positron-Emission Tomography* ; Magnetic Resonance Imaging*; Humans ; Male ; Female ; Aged ; Middle Aged ; Age of Onset ; tau Proteins/metabolism

The objectives of this study were to investigate the variable factors associated with cognitive function and cortical atrophy and estimated variable importance of those factors in affecting cognitive function and cortical atrophy in patients with EOAD and LOAD. Patients with EOAD (n = 40), LOAD (n = 34), and healthy volunteers with normal cognition were included (n = 65). All of them performed 3T MRI, [ ¹⁸ F]THK5351 PET (THK), [ ¹⁸ F]flutemetamol PET (FLUTE), and detailed neuropsychological tests. To investigate factors associated with neuropsychological test results and cortical thickness in each group, we conducted multivariable linear regression models, including amyloid, tau, cerebral small vessel disease markers on MRI, and vascular risk factors. Then, we estimated variable importance in associating cognitive functions and cortical thickness, using relative importance analysis. In patients with EOAD, global THK retention was the most important contributor to the model variances for most neuropsychological tests, except for memory. However, in patients with LOAD, multiple contributors beyond tau were important in explaining variance of neuropsychological tests. In analyses with mean cortical thickness, global THK retention was the main contributor in patients with EOAD, while in LOAD patients, multiple factors contributed equally to mean cortical thickness. Therefore, EOAD and LOAD may have different pathomechanistic courses.
(© 2024. The Author(s).)

Brain. 2017 Sep 1;140(9):2286-2294. (PMID: 29050382)
Can J Neurol Sci. 2012 Nov;39(6):712-28. (PMID: 23227576)
Neuroimage. 2014 May 15;92:225-36. (PMID: 24361666)
Stroke. 2005 Oct;36(10):2116-20. (PMID: 16141425)
Alzheimers Res Ther. 2017 Mar 31;9(1):25. (PMID: 28359327)
Mol Biol Cell. 2013 Aug;24(16):2494-505. (PMID: 23783030)
N Engl J Med. 2023 Jan 5;388(1):9-21. (PMID: 36449413)
J Alzheimers Dis. 2013;35(4):813-21. (PMID: 23507771)
Front Neurosci. 2021 Feb 16;15:606600. (PMID: 33664644)
Transl Psychiatry. 2021 Dec 6;11(1):618. (PMID: 34873149)
Ann N Y Acad Sci. 2002 Nov;977:129-34. (PMID: 12480742)
Neurology. 2016 Aug 2;87(5):539-47. (PMID: 27371494)
Neurobiol Aging. 2014 Sep;35(9):2004-12. (PMID: 24721821)
Int J Mol Sci. 2023 Feb 13;24(4):. (PMID: 36835161)
J Neuroimaging. 2009 Jul;19(3):213-9. (PMID: 19021838)
Neurology. 2005 Aug 23;65(4):545-51. (PMID: 16116114)
Nat Commun. 2016 Jun 21;7:11934. (PMID: 27327500)
Metab Brain Dis. 2022 Jan;37(1):39-50. (PMID: 34406560)
Ann Neurol. 2019 Feb;85(2):272-279. (PMID: 30565287)
Brain. 2017 Dec 1;140(12):3286-3300. (PMID: 29053874)
AJR Am J Roentgenol. 1987 Aug;149(2):351-6. (PMID: 3496763)
PLoS One. 2016 Jun 29;11(6):e0158460. (PMID: 27355840)
Neurology. 2009 Sep 1;73(9):674-80. (PMID: 19720973)
Ann Neurol. 2007 Jul;62(1):59-66. (PMID: 17503514)
Arch Neurol. 2009 Mar;66(3):343-8. (PMID: 19273753)
Neurology. 1996 Jan;46(1):136-41. (PMID: 8559362)
Neurology. 2007 Dec 11;69(24):2197-204. (PMID: 17568013)
Brain. 2014 Jun;137(Pt 6):1762-71. (PMID: 24681664)
Ann Transl Med. 2015 Mar;3(3):38. (PMID: 25815299)
J Alzheimers Dis. 2015;46(2):351-64. (PMID: 25737041)
Neurol Genet. 2020 Oct 6;6(5):e512. (PMID: 33225065)
Neuroimage. 2016 May 15;132:334-343. (PMID: 26915497)
J Geriatr Psychiatry Neurol. 2007 Mar;20(1):29-33. (PMID: 17341768)
Neurobiol Aging. 2013 Jul;34(7):1921.e9-1921.e15. (PMID: 23391426)
JAMA Neurol. 2014 Apr;71(4):505-8. (PMID: 24493463)
Lancet. 2006 Jul 29;368(9533):387-403. (PMID: 16876668)
Brain Pathol. 2006 Jan;16(1):30-9. (PMID: 16612980)
EBioMedicine. 2023 Apr;90:104511. (PMID: 36907103)
Neurology. 1984 Jul;34(7):939-44. (PMID: 6610841)
Neuroimage. 2017 Oct 1;159:224-235. (PMID: 28757193)
J Alzheimers Dis. 2012;30(1):101-8. (PMID: 22366769)
J Nucl Med. 2014 Oct;55(10):1623-8. (PMID: 25146124)
Neurobiol Aging. 2012 Jul;33(7):1156-67. (PMID: 21316813)

HI14C1135 Ministry of Health & Welfare, Republic of Korea; 2021R1A6A1A03038996 Ministry of Education; FRD2022-16 Gachon University Gil Medical Center

Keywords: Age-at-onset; Alzheimer’s disease; Amyloid; Atrophy; Cerebral small vessel disease; Positron emission tomography; Tau; Vascular risk factor

0 (tau Proteins)

Date Created: 20240903 Date Completed: 20240903 Latest Revision: 20240906

20240906

PMC11372067

10.1038/s41598-024-71402-6

39227668