Voxel-based Dysconnectomic Brain Morphometry with Computed Tomography in Down Syndrome

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2023 Dec 30

PMID 38158639

Authors

Beatriz Sanchez-Moreno

Linda Zhang

Gloria Mateo

Fernando Moldenhauer

Mikael Brudfors

John Ashburner

Parashkev Nachev

Diego Real de Asua

Bryan A Strange

Affiliations

Soon will be listed here.

Abstract

Objective: Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort.

Methods: CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated.

Results: Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri.

Interpretation: Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain.

References

Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I . Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study. Lancet. 2020; 395(10242):1988-1997. PMC: 7322523. DOI: 10.1016/S0140-6736(20)30689-9. View

Burt D, Aylward E . Test battery for the diagnosis of dementia in individuals with intellectual disability. Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. J Intellect Disabil Res. 2000; 44 ( Pt 2):175-80. DOI: 10.1046/j.1365-2788.2000.00264.x. View

Del Brutto O, Mera R, Zambrano M, Costa A . The value of the Evans and bicaudate indices for predicting poor cognitive performance and central atrophy. Results from the Atahualpa Project. J Clin Neurosci. 2018; 59:245-247. DOI: 10.1016/j.jocn.2018.08.024. View

Lott I, Head E . Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019; 15(3):135-147. PMC: 8061428. DOI: 10.1038/s41582-018-0132-6. View

Ballard C, Mobley W, Hardy J, Williams G, Corbett A . Dementia in Down's syndrome. Lancet Neurol. 2016; 15(6):622-36. DOI: 10.1016/S1474-4422(16)00063-6. View

Teipel S, Alexander G, Schapiro M, Moller H, Rapoport S, Hampel H . Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain. 2004; 127(Pt 4):811-24. DOI: 10.1093/brain/awh101. View

Devinsky O, Sato S, Conwit R, Schapiro M . Relation of EEG alpha background to cognitive function, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes. Arch Neurol. 1990; 47(1):58-62. DOI: 10.1001/archneur.1990.00530010072022. View

Annus T, Wilson L, Acosta-Cabronero J, Cardenas-Blanco A, Hong Y, Fryer T . The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis. Neurobiol Aging. 2017; 53:11-19. PMC: 5391869. DOI: 10.1016/j.neurobiolaging.2017.01.009. View

Lautarescu B, Holland A, Zaman S . The Early Presentation of Dementia in People with Down Syndrome: a Systematic Review of Longitudinal Studies. Neuropsychol Rev. 2017; 27(1):31-45. PMC: 5359367. DOI: 10.1007/s11065-017-9341-9. View

10.

Pearlson G, Warren A, Starkstein S, Aylward E, Kumar A, Chase G . Brain atrophy in 18 patients with Down syndrome: a CT study. AJNR Am J Neuroradiol. 1990; 11(4):811-6. PMC: 8331631. View

11.

Mattsson N, Cullen N, Andreasson U, Zetterberg H, Blennow K . Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2019; 76(7):791-799. PMC: 6583067. DOI: 10.1001/jamaneurol.2019.0765. View

12.

Zhang Y, Londos E, Minthon L, Wattmo C, Liu H, Aspelin P . Usefulness of computed tomography linear measurements in diagnosing Alzheimer's disease. Acta Radiol. 2008; 49(1):91-7. DOI: 10.1080/02841850701753706. View

13.

Pujol J, Fenoll R, Ribas-Vidal N, Martinez-Vilavella G, Blanco-Hinojo L, Garcia-Alba J . A longitudinal study of brain anatomy changes preceding dementia in Down syndrome. Neuroimage Clin. 2018; 18:160-166. PMC: 5984600. DOI: 10.1016/j.nicl.2018.01.024. View

14.

Iulita M, Garzon Chavez D, Christensen M, Tamayo N, Plana-Ripoll O, Rasmussen S . Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome. JAMA Netw Open. 2022; 5(5):e2212910. PMC: 9127560. DOI: 10.1001/jamanetworkopen.2022.12910. View

15.

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(9):843-852. DOI: 10.1111/jir.12390. View

16.

Olesen P, Guo X, Gustafson D, Borjesson-Hanson A, Sacuiu S, Eckerstrom C . A population-based study on the influence of brain atrophy on 20-year survival after age 85. Neurology. 2011; 76(10):879-86. PMC: 3059146. DOI: 10.1212/WNL.0b013e31820f2e26. View

17.

Fortea J, Carmona-Iragui M, Benejam B, Fernandez S, Videla L, Barroeta I . 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. DOI: 10.1016/S1474-4422(18)30285-0. View

18.

Carmona-Iragui M, Santos T, Videla S, Fernandez S, Benejam B, Videla L . Feasibility of Lumbar Puncture in the Study of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Subjects with Down Syndrome. J Alzheimers Dis. 2016; 55(4):1489-1496. DOI: 10.3233/JAD-160827. View

19.

Rosas H, Hsu E, Mercaldo N, Lai F, Pulsifer M, Keator D . Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?. Alzheimers Dement (Amst). 2020; 12(1):e12040. PMC: 7648416. DOI: 10.1002/dad2.12040. View

20.

Fortea J, Zaman S, Hartley S, Rafii M, Head E, Carmona-Iragui M . Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021; 20(11):930-942. PMC: 9387748. DOI: 10.1016/S1474-4422(21)00245-3. View