Characterization of white matter hyperintensities in Down syndrome.
Alzheimer's disease
Down syndrome
magnetic resonance imaging
neuroimaging
small vessel disease
white matter hyperintensities
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
revised:
20
06
2024
received:
06
03
2024
accepted:
02
07
2024
medline:
1
8
2024
pubmed:
1
8
2024
entrez:
1
8
2024
Statut:
aheadofprint
Résumé
In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI18/00335
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI18/00435
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI14/1561
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI20/01330
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI20/01473
Organisme : Instituto de Salud Carlos III and co-funded by the European Union
ID : PI22/00307
Organisme : National Institutes of Health (NIH)
ID : 1R01AG056850-01A1
Organisme : National Institutes of Health (NIH)
ID : 3RF1AG056850-01S1
Organisme : National Institutes of Health (NIH)
ID : AG056850
Organisme : National Institutes of Health (NIH)
ID : R21AG056974
Organisme : National Institutes of Health (NIH)
ID : R01AG061566
Organisme : Horizon 2020, "MES-CoBraD"
ID : H2020-SC1-BHC-2018-2020
Organisme : Horizon 2020, "MES-CoBraD"
ID : GA 965422
Organisme : Instituto de Salud Carlos III and co-funded by the European Union through the Predoctoral grant
ID : FI18/00275
Organisme : Juan de la Cierva fellowship
ID : JDC2022-048492-I
Organisme : Alzheimer's Association and Global Brain Health Institute
ID : GBHI_ALZ-18-543740
Organisme : Jérôme Lejeune Foundation
Organisme : Societat Catalana de Neurologia (Premi Beca Fundació SCN 2020)
Organisme : Alzheimer's Association Research Fellowship to Promote Diversity
ID : AARFD-21-852492
Organisme : Margarita Salas junior postdoctoral fellowship
ID : UNI/551/2021
Organisme : Instituto de Salud Carlos III and co-funded by the European Union through the Sara Borrell Postdoctoral Fellowship
ID : CD20/00133
Organisme : Instituto de Salud Carlos III and co-funded by the European Union through the Río Hortega Fellowship
ID : CM22/00219
Organisme : Instituto de Salud Carlos III and co-funded by the European Union through the Río Hortega Fellowship
ID : CM21/00243
Organisme : Instituto de Salud Carlos III and co-funded by the European Union through the Miguel Servet Fellowship
ID : CP20/00038
Organisme : Alzheimer's Association
ID : AARG-22-923680
Pays : United States
Organisme : Fundación Tatiana Pérez de Guzmán el Bueno
ID : IIBSP-DOW-2020-151
Informations de copyright
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019;15:135‐147. 2019 153. doi:10.1038/s41582‐018‐0132‐6
Fortea J, Vilaplana E, Carmona‐Iragui M, et al. Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross‐sectional study. Lancet. 2020;395:1988‐1997. doi:10.1016/S0140‐6736(20)30689‐9
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona‐Iragui M. Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021;20:930‐942. doi:10.1016/S1474‐4422(21)00245‐3
McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20‐year longitudinal follow‐up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2017;61:843‐852. doi:10.1111/JIR.12390
Iulita MF, Garzón Chavez D, Klitgaard Christensen M, et al. Association of Alzheimer disease with life expectancy in people with Down syndrome. JAMA Netw Open. 2022;5:e2212910‐e2212910. doi:10.1001/JAMANETWORKOPEN.2022.12910
Carmona‐Iragui M, Videla L, Lleó A, Fortea J. Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: the complex triangle of brain amyloidosis. Dev Neurobiol. 2019;79:716‐737. doi:10.1002/DNEU.22709
Draheim CC, Geijer JR, Dengel DR. Comparison of intima‐media thickness of the carotid artery and cardiovascular disease risk factors in adults with versus without the Down syndrome. Am J Cardiol. 2010;106:1512‐1516. doi:10.1016/J.AMJCARD.2010.06.079
Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019;18:684‐696. doi:10.1016/S1474‐4422(19)30079‐1
Gaubert M, Lange C, Garnier‐Crussard A, et al. Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer's disease. Alzheimer's Res Ther. 2021;13:1‐11. 2021 131. doi:10.1186/S13195‐020‐00759‐3
Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol. 2015;11:157‐165. 2015 113. doi:10.1038/nrneurol.2015.10
ter Telgte A, van Leijsen EMC, Wiegertjes K, Klijn CJM, Tuladhar AM, de Leeuw F‐E. Cerebral small vessel disease: from a focal to a global perspective. Nat Rev Neurol. 2018;14:387‐398. 2018 147. doi:10.1038/s41582‐018‐0014‐y
Garnier‐Crussard A, Cotton F, Krolak‐Salmon P, Chételat G. White matter hyperintensities in Alzheimer's disease: beyond vascular contribution. Alzheimer's Dement. 2023;19:3738‐3748. doi:10.1002/ALZ.13057
Garnier‐Crussard A, Bougacha S, Wirth M, et al. White matter hyperintensity topography in Alzheimer's disease and links to cognition. Alzheimer's Dement. 2022;18:422‐433. doi:10.1002/ALZ.12410
Lee S, Viqar F, Zimmerman ME, et al. White matter hyperintensities are a core feature of Alzheimer's disease: evidence from the dominantly inherited Alzheimer network. Ann Neurol. 2016;79:929‐939. doi:10.1002/ANA.24647
Schoemaker D, Zanon Zotin MC, Chen K, et al. White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer's disease that emerge prior to dementia. Alzheimer's Res Ther. 2022;14:1‐11. doi:10.1186/S13195‐022‐01030‐7/FIGURES/3
Carmona‐Iragui M, Balasa M, Benejam B, et al. Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal‐dominant Alzheimer's disease. Alzheimer's Dement. 2017;13:1251‐1260. doi:10.1016/J.JALZ.2017.03.007
Lao PJ, Gutierrez J, Keator D, et al. Alzheimer‐related cerebrovascular disease in Down syndrome. Ann Neurol. 2020;88:1165‐1177. doi:10.1002/ANA.25905
Alcolea D, Clarimón J, Carmona‐Iragui M, et al. The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: a data set for biomarker discovery and validation in neurodegenerative disorders. Alzheimer's Dement Transl Res Clin Interv. 2019;5:597‐609. doi:10.1016/J.TRCI.2019.09.005
Hon J, Huppert FA, Holland AJ, Watson P. Neuropsychological assessment of older adults with Down's Syndrome: an epidemiological study using the Cambridge Cognitive Examination (CAMCOG). Br J Clin Psychol. 1999;38:155‐165. doi:10.1348/014466599162719
Esteba‐Castillo S, Dalmau‐Bueno A, Ribas‐Vidal N, Vilá‐Alsina M, García Alba J, Novell R. Adaptation and validation of CAMDEX‐DS (Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and others with intellectual disabilities) in Spanish population with intellectual disabilities [in Spanish]. Rev Neurol. 2013;57:337‐346. ISSN 0210‐0010, Vol 57, No 8, 2013, Págs 337‐346.
Fortea J, Carmona‐Iragui M, Benejam B, et al. Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross‐sectional study. Lancet Neurol. 2018;17:860‐869. doi:10.1016/S1474‐4422(18)30285‐0
Regier DA, Kuhl EA, Kupfer DJ. The DSM‐5: classification and criteria changes. World Psychiatry. 2013;12:92‐98. doi:10.1002/WPS.20050
Gaser C, Dahnke R, Thompson PM, Kurth F, Luders E, Initiative ADN. CAT – a computational anatomy toolbox for the analysis of structural MRI data. Biorxiv. 2022:11.495736. doi:10.1101/2022.06.11.495736. 2022.06.. bioRxiv.
Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54:2033‐2044. doi:10.1016/J.NEUROIMAGE.2010.09.025
Schmidt P, Bayesian inference for structured additive regression models for large‐scale problems with applications to medical imaging 2017. (accessed April 16, 2022) https://edoc.ub.uni‐muenchen.de/20373/
Sudre CH, Gomez Anson B, Davagnanam I, et al. Bullseye's representation of cerebral white matter hyperintensities. J Neuroradiol. 2018;45:114‐122. doi:10.1016/J.NEURAD.2017.10.001
Jiménez‐Balado J, Corlier F, Habeck C, Stern Y, Eich T. Effects of white matter hyperintensities distribution and clustering on late‐life cognitive impairment. Sci Rep. 2022;12:1‐13. 2022 121. doi:10.1038/s41598‐022‐06019‐8
Orlhac F, Eertink JJ, Cottereau AS, et al. A guide to ComBat harmonization of imaging biomarkers in multicenter studies. J Nucl Med. 2022;63(2):172‐179. doi:10.2967/JNUMED.121.262464
Carmona‐Iragui M, Santos T, Videla S, et al. Feasibility of lumbar puncture in the study of cerebrospinal fluid biomarkers for Alzheimer's disease in subjects with Down syndrome. J Alzheimer's Dis. 2017;55:1489‐1496. doi:10.3233/JAD‐160827
Alcolea D, Pegueroles J, Muñoz L, et al. Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse. Ann Clin Transl Neurol. 2019;6:1815‐1824. doi:10.1002/ACN3.50873
Subirana I, Sanz H, Vila J. Building Bivariate Tables: the compareGroups Package for R. J Stat Softw. 2014;57:1‐16. doi:10.18637/JSS.V057.I12
Garnier‐Crussard A, Bougacha S, Wirth M, et al. White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition. Alzheimer's Res Ther. 2020;12:1‐11. 2020 121. doi:10.1186/S13195‐020‐00669‐4
Hopkins RO, Beck CJ, Burnett DL, Weaver LK, Victoroff J, Bigler ED. Prevalence of white matter hyperintensities in a young healthy population. J Neuroimaging. 2006;16:243‐251. doi:10.1111/J.1552‐6569.2006.00047.X
Holland CM, Smith EE, Csapo I, et al. Spatial distribution of white‐matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke. 2008;39:1127. doi:10.1161/STROKEAHA.107.497438
Iulita MF, Bejanin A, Vilaplana E, et al. Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome. Brain Commun. 2023;5:14. doi:10.1093/BRAINCOMMS/FCAD074
Bejanin A, Iulita MF, Vilaplana E, et al. Association of apolipoprotein E ɛ4 allele with clinical and multimodal biomarker changes of Alzheimer disease in adults with Down syndrome. JAMA Neurol. 2021;78:937‐947. doi:10.1001/JAMANEUROL.2021.1893
Operto G, Cacciaglia R, Grau‐Rivera O, et al. White matter microstructure is altered in cognitively normal middle‐aged APOE‐ε4 homozygotes. Alzheimers Res Ther. 2018;10(1):48. doi:10.1186/S13195‐018‐0375‐X
Rojas S, Brugulat‐Serrat A, Bargalló N, et al. Higher prevalence of cerebral white matter hyperintensities inhomozygous APOE‐ɛ4 allele carriers aged 45‐75: results from theALFA study. J Cereb Blood Flow Metab. 2018;38:250. doi:10.1177/0271678x17707397
Habes M, Erus G, Toledo JB, et al. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain. 2016;139:1164. doi:10.1093/BRAIN/AWW008
Kumar D, Yatawara C, Wang B, et al. APOE4 and confluent white matter hyperintensities have a synergistic effect on episodic memory impairment in prodromal dementia. J Alzheimer's Dis. 2022;87:1103‐1114. doi:10.3233/JAD‐215556
Slattery CF, Zhang J, Paterson RW, et al. ApoE influences regional white‐matter axonal density loss in Alzheimer's disease. Neurobiol Aging. 2017;57:8. doi:10.1016/J.NEUROBIOLAGING.2017.04.021
Morgen K, Schneider M, Frölich L, et al. Apolipoprotein E‐dependent load of white matter hyperintensities in Alzheimer's disease: a voxel‐based lesion mapping study. Alzheimers Res Ther. 2015;7(1):27. doi:10.1186/S13195‐015‐0111‐8
Hartley SL, Fleming V, Schworer EK, et al. Timing of Alzheimer's disease by intellectual disability level in Down syndrome. J Alzheimers Dis. 2023;95:213‐225. doi:10.3233/JAD‐230200
Videla L, Benejam B, Pegueroles J, et al. Longitudinal clinical and cognitive changes along the Alzheimer disease continuum in Down syndrome. JAMA Netw Open. 2022;5:e2225573‐e2225573. doi:10.1001/JAMANETWORKOPEN.2022.25573
Eloyan A, Thangarajah M, An N, et al. White matter hyperintensities are higher among early‐onset Alzheimer's disease participants than their cognitively normal and early‐onset nonAD peers: longitudinal Early‐onset Alzheimer's Disease Study (LEADS). Alzheimer's Dement. 2023;19(9):S89‐S97. doi:10.1002/alz.13402. Suppl.
Brickman AM, Zahodne LB, Guzman VA, et al. Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence. Neurobiol Aging. 2015;36:27‐32. doi:10.1016/J.NEUROBIOLAGING.2014.07.019
Walsh P, Sudre CH, Manning EN, et al. White matter hyperintensity increases are a feature of familial AD and are associated with increased brain atrophy. Alzheimer's Dement. 2020;16:e038925. doi:10.1002/ALZ.038925
Yoshita M, Fletcher E, Harvey D, et al. Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology. 2006;67:2192. doi:10.1212/01.WNL.0000249119.95747.1F
Mayo CD, Garcia‐Barrera MA, Mazerolle EL, Ritchie LJ, Fisk JD, Gawryluk JR. Relationship between DTI metrics and cognitive function in Alzheimer's disease. Front Aging Neurosci. 2019;10:436. doi:10.3389/FNAGI.2018.00436
Weaver NA, Doeven T, Barkhof F, et al. Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions. Neurobiol Aging. 2019;84:225‐234. doi:10.1016/J.NEUROBIOLAGING.2019.08.001
Caballero MÁA, Song Z, Rubinski A, et al. Age‐dependent amyloid deposition is associated with white matter alterations in cognitively normal adults during the adult life span. Alzheimer's Dement. 2020;16:651‐661. doi:10.1002/ALZ.12062
Roseborough A, Ramirez J, Black SE, Edwards JD. Associations between amyloid β and white matter hyperintensities: a systematic review. Alzheimer's Dement. 2017;13:1154‐1167. doi:10.1016/J.JALZ.2017.01.026
Graff‐Radford J, Arenaza‐Urquijo EM, Knopman DS, et al. White matter hyperintensities: relationship to amyloid and tau burden. Brain. 2019;142:2483‐2491. doi:10.1093/BRAIN/AWZ162
Osborn KE, Liu D, Samuels LR, et al. Cerebrospinal fluid β‐amyloid42 and neurofilament light relate to white matter hyperintensities. Neurobiol Aging. 2018;68:18‐25. doi:10.1016/J.NEUROBIOLAGING.2018.03.028
Van Waalwijk Van Doorn LJC, Ghafoorian M, Van Leijsen EMC, et al. White matter hyperintensities are no major confounder for Alzheimer's disease cerebrospinal fluid biomarkers. J Alzheimers Dis. 2021;79:163‐175. doi:10.3233/JAD‐200496
Pålhaugen L, Sudre CH, Tecelao S, et al. Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns. J Cereb Blood Flow Metab. 2021;41:1162. doi:10.1177/0271678x20957604
Walsh P, Sudre CH, Fiford CM, et al. CSF amyloid is a consistent predictor of white matter hyperintensities across the disease course from aging to Alzheimer's disease. Neurobiol Aging. 2020;91:5‐14. doi:10.1016/J.NEUROBIOLAGING.2020.03.008
Walsh P, Sudre CH, Fiford CM, et al. The age‐dependent associations of white matter hyperintensities and neurofilament light in early‐ and late‐stage Alzheimer's disease. Neurobiol Aging. 2021;97:10‐17. doi:10.1016/J.NEUROBIOLAGING.2020.09.008
Zetterberg H, Skillbäck T, Mattsson N, et al. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol. 2016;73:60. doi:10.1001/JAMANEUROL.2015.3037
Meeker KL, Butt OH, Gordon BA, et al. Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage. Neurobiol Dis. 2022;166:105662. doi:10.1016/J.NBD.2022.105662
Schultz SA, Strain JF, Adedokun A, et al. Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease. Neurobiol Dis. 2020;142:104960. doi:10.1016/J.NBD.2020.104960
Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90:870‐881. doi:10.1136/JNNP‐2018‐320106
La Joie R, Visani AV, Baker SL, et al. Prospective longitudinal atrophy in Alzheimer's disease correlates with the intensity and topography of baseline tau‐PET. Sci Transl Med. 2020;12(254):eaau5732. doi:10.1126/SCITRANSLMED.AAU5732
Dickerson BC, Bakkour A, Salat DH, et al. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid‐positive individuals. Cereb Cortex (New York, NY). 2009;19:497. doi:10.1093/CERCOR/BHN113
Lao PJ, Brickman AM. Multimodal neuroimaging study of cerebrovascular disease, amyloid deposition, and neurodegeneration in Alzheimer's disease progression. Alzheimer's Dement Diagnosis, Assess Dis Monit. 2018;10:638‐646. doi:10.1016/J.DADM.2018.08.007
Brickman AM, Rizvi B. White matter hyperintensities and Alzheimer's disease: an alternative view of an alternative hypothesis. Alzheimer's Dement. 2023;19:4260‐4261. doi:10.1002/ALZ.13371
Bozzali M, Falini A, Franceschi M, et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2002;72:742. doi:10.1136/JNNP.72.6.742
McAleese KE, Walker L, Graham S, et al. Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease. Acta Neuropathol. 2017;134:459‐473. doi:10.1007/S00401‐017‐1738‐2/FIGURES/5
McAleese KE, Firbank M, Dey M, et al. Cortical tau load is associated with white matter hyperintensities 2015. doi:10.1186/s40478‐015‐0240‐0
Salvadores N, Gerónimo‐Olvera C, Court FA. Axonal degeneration in AD: the contribution of Aβ and Tau. Front Aging Neurosci. 2020;12:581767. doi:10.3389/FNAGI.2020.581767/BIBTEX
Laing KK, Simoes S, Baena‐Caldas GP, et al. Cerebrovascular disease promotes tau pathology in Alzheimer's disease. Brain Commun. 2020;2(2):fcaa132. doi:10.1093/BRAINCOMMS/FCAA132
Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844‐866. doi:10.1016/J.NEURON.2013.10.008
Thanprasertsuk S, Martinez‐Ramirez S, Pontes‐Neto OM, et al. Posterior white matter disease distribution as a predictor of amyloid angiopathy. Neurology. 2014;83:794‐800. doi:10.1212/WNL.0000000000000732
Garnier‐Crussard A, Cotton F, Krolak‐Salmon P, Chételat G. White matter hyperintensities in Alzheimer's disease: beyond vascular contribution. Alzheimer's Dement. 2023;19(8):3738‐3748. doi:10.1002/ALZ.13057
Low A, Mak E, Rowe JB, Markus HS, O'Brien JT. Inflammation and cerebral small vessel disease: a systematic review. Ageing Res Rev. 2019;53:100916. doi:10.1016/J.ARR.2019.100916