Cholinergic white matter pathways along the Alzheimer's disease continuum.
Alzheimer’s disease
CSF markers
MRI
cholinergic system
nucleus basalis of Meynert
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
02 05 2023
02 05 2023
Historique:
received:
12
06
2022
revised:
12
09
2022
accepted:
19
09
2022
medline:
3
5
2023
pubmed:
27
10
2022
entrez:
26
10
2022
Statut:
ppublish
Résumé
Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.
Identifiants
pubmed: 36288546
pii: 6775152
doi: 10.1093/brain/awac385
pmc: PMC10151179
doi:
Substances chimiques
Cholinergic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2075-2088Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
Références
Lancet Neurol. 2009 Jul;8(7):619-27
pubmed: 19523877
Neuroimage. 2019 Apr 1;189:180-191
pubmed: 30630081
J Alzheimers Dis. 2013;35(1):129-36
pubmed: 23364137
Nat Commun. 2016 Nov 04;7:13249
pubmed: 27811848
J Intern Med. 2015 Aug;278(2):211-8
pubmed: 25639959
Magn Reson Med. 1998 Feb;39(2):328-30
pubmed: 9469719
Neuron. 2016 Sep 21;91(6):1199-1218
pubmed: 27657448
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Neurobiol Aging. 2014 Mar;35(3):482-91
pubmed: 24176625
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Arch Gen Psychiatry. 2012 Jan;69(1):98-106
pubmed: 22213792
Alzheimers Dement. 2014 Nov;10(6):844-52
pubmed: 24798886
Brain. 1998 Dec;121 ( Pt 12):2249-57
pubmed: 9874478
Brain. 2020 Mar 1;143(3):993-1009
pubmed: 32203580
J Alzheimers Dis. 2011;23(2):319-26
pubmed: 21098971
Hum Brain Mapp. 2014 Mar;35(3):1085-100
pubmed: 23362153
Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S13-21
pubmed: 9236948
Alzheimers Dement. 2011 May;7(3):270-9
pubmed: 21514249
Neuroimage Clin. 2014 Aug 28;6:115-25
pubmed: 25379423
Neurology. 2022 Mar 29;98(13):e1315-e1326
pubmed: 35110378
J Intern Med. 2014 Apr;275(4):418-27
pubmed: 24237038
Neuroimage. 2014 May 15;92:381-97
pubmed: 24530839
Lancet Neurol. 2013 Apr;12(4):357-67
pubmed: 23477989
Nat Commun. 2017 Oct 31;8(1):1214
pubmed: 29089479
Magn Reson Med. 1995 Jul;34(1):65-73
pubmed: 7674900
Ann Clin Transl Neurol. 2016 Jan 01;3(3):154-65
pubmed: 27042676
IEEE Trans Med Imaging. 2001 Jan;20(1):45-57
pubmed: 11293691
Radiology. 2004 Jan;230(1):77-87
pubmed: 14645885
Neurology. 2022 Oct 11;99(15):e1619-e1629
pubmed: 35918153
Nat Neurosci. 2018 Oct;21(10):1350-1358
pubmed: 30250262
Alzheimers Dement. 2016 Mar;12(3):292-323
pubmed: 27012484
Hum Brain Mapp. 2002 Nov;17(3):143-55
pubmed: 12391568
Brain. 2022 Jun 3;145(5):1773-1784
pubmed: 34605858
Neuroimage. 2012 Aug 15;62(2):782-90
pubmed: 21979382
J Neural Transm (Vienna). 2011 Feb;118(2):259-62
pubmed: 21161712
Magn Reson Med. 2003 Nov;50(5):1077-88
pubmed: 14587019
Science. 1982 Jul 30;217(4558):408-14
pubmed: 7046051
Sci Rep. 2017 Mar 13;7:44368
pubmed: 28287184
Neuroimage. 2007 Jan 1;34(1):144-55
pubmed: 17070705
J Investig Med. 2014 Oct;62(7):927-33
pubmed: 25046178
J Alzheimers Dis. 2015;48(1):197-204
pubmed: 26401940
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Nat Rev Neurol. 2018 Aug;14(8):496-506
pubmed: 29980763
Neuroimage. 2020 May 1;211:116607
pubmed: 32035186
Brain. 2018 May 1;141(5):1501-1516
pubmed: 29701787
BMC Bioinformatics. 2007 Jan 25;8:25
pubmed: 17254353
Exp Neurol. 2013 Aug;246:44-53
pubmed: 22721767
Front Aging Neurosci. 2020 Dec 15;12:608667
pubmed: 33384594
Brain. 2022 Aug 27;145(8):2869-2881
pubmed: 35259207
Alzheimers Res Ther. 2021 Feb 8;13(1):38
pubmed: 33557920
Neuroimage. 2004 Oct;23(2):724-38
pubmed: 15488422
Neuron. 2002 Jan 31;33(3):341-55
pubmed: 11832223
Neuroimage. 2016 Jan 15;125:1063-1078
pubmed: 26481672
J Alzheimers Dis. 2019;72(2):455-465
pubmed: 31594223
Neurology. 2020 Sep 1;95(9):e1134-e1143
pubmed: 32636322
Brain. 2018 Mar 1;141(3):877-887
pubmed: 29365053
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
Neurobiol Aging. 2021 Aug;104:24-31
pubmed: 33962331
J Alzheimers Dis. 2014;40(3):687-700
pubmed: 24503619
Aging (Albany NY). 2020 Jan 12;12(1):894-901
pubmed: 31927535
PLoS One. 2013 Apr 29;8(4):e61892
pubmed: 23658616
Alzheimers Res Ther. 2018 Feb 07;10(1):15
pubmed: 29415768
Alzheimers Dement. 2011 May;7(3):280-92
pubmed: 21514248