Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.
Alzheimer's disease
Down syndrome
cerebral amyloid angiopathy
cerebral microbleeds
cortical microinfarcts
magnetic resonance imaging
neuroimaging
small vessel diseases
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:
21 Apr 2024
21 Apr 2024
Historique:
revised:
01
02
2024
received:
29
08
2023
accepted:
22
02
2024
medline:
22
4
2024
pubmed:
22
4
2024
entrez:
22
4
2024
Statut:
aheadofprint
Résumé
Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.
Sections du résumé
BACKGROUND
BACKGROUND
Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS.
METHODS
METHODS
We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS.
RESULTS
RESULTS
CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions.
DISCUSSION
CONCLUSIONS
In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype.
HIGHLIGHTS
CONCLUSIONS
This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : 1R01AG056850-01A1
Pays : United States
Organisme : NIH HHS
ID : 3RF1AG056850-01S1
Pays : United States
Organisme : NIH HHS
ID : AG056850
Pays : United States
Organisme : NIH HHS
ID : R21AG056974
Pays : United States
Organisme : NIH HHS
ID : R01AG061566
Pays : United States
Organisme : Alzheimer's Association
ID : AARG-22-923680
Pays : United States
Informations de copyright
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Smith EE, Schneider JA, Wardlaw JM, Greenberg SM. Cerebral microinfarcts: the invisible lesions. Lancet Neurol. 2012;11(3):272‐282.
van Veluw SJ, Zwanenburg JJM, Engelen‐Lee J, et al. In vivo detection of cerebral cortical microinfarcts with high‐resolution 7T MRI. J Cereb Blood Flow Metab. 2013;33(3):322‐329.
van Veluw SJ, Biessels GJ, Luijten PR, Zwanenburg JJM. Assessing cortical cerebral microinfarcts on high resolution MR images. J Vis Exp. 2015(105):53125.
van Dalen JW, Scuric EEM, van Veluw SJ, et al. Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates. Stroke. 2015;46(1):255‐257.
Ferro D, van den Brink H, Amier R, et al. Cerebral cortical microinfarcts: a novel MRI marker of vascular brain injury in patients with heart failure. Int J Cardiol. 2020;310:96‐102.
Hilal S, Chai YL, van Veluw S, et al. Association between subclinical cardiac biomarkers and clinically manifest cardiac diseases with cortical cerebral microinfarcts. JAMA Neurol. 2017;74(4):403‐410.
Ferro DA, Mutsaerts HJ, Hilal S, et al. Cortical microinfarcts in memory clinic patients are associated with reduced cerebral perfusion. J Cereb Blood Flow Metab. 2019;40(9):271678×19877403.
van den Brink H, Ferro DA, de BresserJ, et al. Cerebral cortical microinfarcts in patients with internal carotid artery occlusion. J Cereb Blood Flow Metab. 2021. Published online.
van Veluw SJ, Hilal S, Kuijf HJ, et al. Cortical microinfarcts on 3T MRI: clinical correlates in memory‐clinic patients. Alzheimers Dement. 2015;11(12):1500‐1509.
Lauer A, van Veluw SJ, William CM, et al. Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral amyloid angiopathy. Neurology. 2016;87(14):1488‐1492.
van Veluw SJ, Scherlek AA, Freeze WM, et al. Different microvascular alterations underlie microbleeds and microinfarcts. Ann Neurol. 2019;86(2):279‐292.
van den Brink H, Zwiers A, Switzer AR, et al. Cortical microinfarcts on 3T magnetic resonance imaging in cerebral amyloid angiopathy. Stroke. 2018;49(8):1899‐1905.
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(7):716‐737.
Carmona‐Iragui M, Balasa M, Benejam B, et al. Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal‐dominant Alzheimer's disease. Alzheimers Dement. 2017;13(11):1251‐1260.
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(11):930‐942.
Lao PJ, Gutierrez J, Keator D, et al. Alzheimer‐related cerebrovascular disease in down syndrome. Ann Neurol. 2020;88(6):1165‐1177.
Kerins G, Petrovic K, Bruder MB, Gruman C. Medical conditions and medication use in adults with Down syndrome: a descriptive analysis. Downs Syndr Res Pract. 2008;12(2):141‐147.
Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down's syndrome: an atheroma‐free model? Br Med J. 1977;2(6081):226‐228.
Pucci F, Machado G, Solera E, et al. Blood pressure levels and body mass index in Brazilian adults with Down syndrome. Sao Paulo Med J. 2016;134(4):330‐334.
Kapell D, Nightingale B, Rodriguez A, Lee JH, Zigman WB, Schupf N. Prevalence of chronic medical conditions in adults with mental retardation: comparison with the general population. Ment Retard. 1998;36(4):269‐279.
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. Alzheimers Dement. 2019;5:597‐609.
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(10242):1988‐1997.
Kaufman AS, Kaufman NL. KBIT2: Kaufmann Brief Intelligence Test. 3rd Ed. Pearson/PsychCorp; 2004.
Ball SL, Holland AJ, Huppert FA, Treppner P, Watson P, Hon J. The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome. J Intellect Disabil Res. 2004;48(6):611‐620. Pt.
Esteba‐Castillo S, Dalmau‐Bueno A, Ribas‐Vidal N, Vilà‐Alsina M, Novell‐Alsina R, García‐Alba J. 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. Rev Neurol. 2013;57(8):337‐346.
Devenny DA, Zimmerli EJ, Kittler P, Krinsky‐McHale SJ. Cued recall in early‐stage dementia in adults with Down's syndrome. J Intellect Disabil Res. 2002;46(6):472‐483. Pt.
Arevalo‐Rodriguez I, Smailagic N, Roqué‐Figuls M, et al. Mini‐Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2021;7(7):CD010783.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263‐269.
Benejam B, Videla L, Vilaplana E, et al. Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests. Alzheimers Dement. 2020;12(1):e12047.
Tustison NJ, Avants BB, Cook PA, et al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging. 2010;29(6):1310‐1320.
Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822‐838.
Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010;74(17):1346‐1350.
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(9):1815‐1824.
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422‐433.
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(10):860‐869.
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(8):937‐947.
Ferro DA, Kuijf HJ, Hilal S, et al. Association between cerebral cortical microinfarcts and perilesional cortical atrophy on 3T MRI. Neurology. 2022;98(6):e612‐e622.
Xu X, Ni Kan C, Li‐Hsian Chen C, Hilal S. Long‐term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore. Int J Stroke. 2021:17474930211006294. Published online. April 7,.
Ferro D, Heinen R, de Brito Robalo B, Kuijf H, Biessels GJ, Reijmer Y. Cortical microinfarcts and white matter connectivity in memory clinic patients. Front Neurol. 2019;10:571.
Hilal S, Doolabi A, Vrooman H, Ikram MK, Ikram MA, Vernooij MW. Clinical relevance of cortical cerebral microinfarcts on 1.5T magnetic resonance imaging in the late‐adult population. Stroke. 2021;52(3):922‐930.
Gokcal E, Horn MJ, van Veluw SJ, et al. Lacunes, microinfarcts, and vascular dysfunction in cerebral amyloid angiopathy. Neurology. 2021;96(12):e1646‐e1654.
Xiong L, van Veluw SJ, Bounemia N, et al. Cerebral cortical microinfarcts on magnetic resonance imaging and their association with cognition in cerebral amyloid angiopathy. Stroke. 2018;49(10):2330‐2336.
Takasugi J, Miwa K, Watanabe Y, et al. Cortical cerebral microinfarcts on 3t magnetic resonance imaging in patients with carotid artery stenosis. Stroke. 2019;50(3):639‐644.
Morrison RA, McGrath A, Davidson G, Brown JJ, Murray GD, Lever AF. Low blood pressure in Down's syndrome, A link with Alzheimer's disease? Hypertension. 1996;28(4):569‐575.
Suter OC, Sunthorn T, Kraftsik R, et al. Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease. Stroke. 2002;33(8):1986‐1992.
Kövari E, Herrmann FR, Gold G, Hof PR, Charidimou A. Association of cortical microinfarcts and cerebral small vessel pathology in the ageing brain. Neuropathol Appl Neurobiol. 2017;43(6):505‐513.
Yilmazer‐Hanke D, Mayer T, Müller HP, et al. Histological correlates of postmortem ultra‐high‐resolution single‐section MRI in cortical cerebral microinfarcts. Acta Neuropathol Commun. 2020;8(1):33.
Ferro DA, van den Brink H, Exalto LG, et al. Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment. Neurology. 2019;92(14):e1558‐e1566.
Charidimou A, Friedrich JO, Greenberg SM, Viswanathan A. Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: a meta‐analysis. Neurology. 2018;90(9):e754‐e762.