MRI Free Water As a Biomarker for Cognitive Performance: Validation in the MarkVCID Consortium

Overview

Journal Alzheimers Dement (Amst)

Date 2022 Dec 16

PMID 36523847

Authors

Pauline Maillard

Laura J Hillmer

Hanzhang Lu

Konstantinos Arfanakis

Brian T Gold

Christopher E Bauer

Joel H Kramer

Adam M Staffaroni

Lara Stables

Danny J J Wang

Sudha Seshadri

Claudia L Satizabal

Alexa Beiser

Mohamad Habes

Myriam Fornage

Thomas H Mosley

Gary A Rosenberg

Baljeet Singh

Herpreet Singh

Kristin Schwab

Karl G Helmer

Steven M Greenberg

Charles DeCarli

Arvind Caprihan

Affiliations

Soon will be listed here.

Abstract

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).

Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores ( = 0.0026).

Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

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References

Lu H, Kashani A, Arfanakis K, Caprihan A, DeCarli C, Gold B . MarkVCID cerebral small vessel consortium: II. Neuroimaging protocols. Alzheimers Dement. 2021; 17(4):716-725. PMC: 8627001. DOI: 10.1002/alz.12216. View

Altendahl M, Maillard P, Harvey D, Cotter D, Walters S, Wolf A . An IL-18-centered inflammatory network as a biomarker for cerebral white matter injury. PLoS One. 2020; 15(1):e0227835. PMC: 6980497. DOI: 10.1371/journal.pone.0227835. View

Makkinejad N, Evia A, Tamhane A, Javierre-Petit C, Leurgans S, Lamar M . ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain. Neuroimage Clin. 2021; 31:102768. PMC: 8329541. DOI: 10.1016/j.nicl.2021.102768. View

Staffaroni A, Bajorek L, Casaletto K, Cobigo Y, Goh S, Wolf A . Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint. Alzheimers Dement. 2020; 16(1):11-21. PMC: 6842665. DOI: 10.1016/j.jalz.2019.01.012. View

Edde M, Theaud G, Rheault F, Dilharreguy B, Helmer C, Dartigues J . Free water: A marker of age-related modifications of the cingulum white matter and its association with cognitive decline. PLoS One. 2020; 15(11):e0242696. PMC: 7678997. DOI: 10.1371/journal.pone.0242696. View

Vipin A, Ng K, Ji F, Shim H, Lim J, Pasternak O . Amyloid burden accelerates white matter degradation in cognitively normal elderly individuals. Hum Brain Mapp. 2019; 40(7):2065-2075. PMC: 6501192. DOI: 10.1002/hbm.24507. View

Wright J, Folsom A, Coresh J, Sharrett A, Couper D, Wagenknecht L . The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8. J Am Coll Cardiol. 2021; 77(23):2939-2959. PMC: 8667593. DOI: 10.1016/j.jacc.2021.04.035. View

Hoy A, Ly M, Carlsson C, Okonkwo O, Zetterberg H, Blennow K . Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging. PLoS One. 2017; 12(3):e0173982. PMC: 5349685. DOI: 10.1371/journal.pone.0173982. View

Gullett J, OShea A, Lamb D, Porges E, OShea D, Pasternak O . The association of white matter free water with cognition in older adults. Neuroimage. 2020; 219:117040. PMC: 7429363. DOI: 10.1016/j.neuroimage.2020.117040. View

10.

Hamilton O, Backhouse E, Janssen E, Jochems A, Maher C, Ritakari T . Cognitive impairment in sporadic cerebral small vessel disease: A systematic review and meta-analysis. Alzheimers Dement. 2020; 17(4):665-685. PMC: 8593445. DOI: 10.1002/alz.12221. View

11.

Berger M, Pirpamer L, Hofer E, Ropele S, Duering M, Gesierich B . Free water diffusion MRI and executive function with a speed component in healthy aging. Neuroimage. 2022; 257:119303. PMC: 9465649. DOI: 10.1016/j.neuroimage.2022.119303. View

12.

Dumont M, Roy M, Jodoin P, Morency F, Houde J, Xie Z . Free Water in White Matter Differentiates MCI and AD From Control Subjects. Front Aging Neurosci. 2019; 11:270. PMC: 6783505. DOI: 10.3389/fnagi.2019.00270. View

13.

Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser M, Guillon P . Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation. 2005; 112(11):1644-50. DOI: 10.1161/CIRCULATIONAHA.104.501163. View

14.

Nasrallah I, Pajewski N, Auchus A, Chelune G, Cheung A, Cleveland M . Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions. JAMA. 2019; 322(6):524-534. PMC: 6692679. DOI: 10.1001/jama.2019.10551. View

15.

Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y . Free water elimination and mapping from diffusion MRI. Magn Reson Med. 2009; 62(3):717-30. DOI: 10.1002/mrm.22055. View

16.

Reas E, Hagler D, Kuperman J, Wierenga C, Galasko D, White N . Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia. J Alzheimers Dis. 2019; 73(1):347-357. PMC: 7266036. DOI: 10.3233/JAD-190871. View

17.

Bergamino M, Walsh R, Stokes A . Free-water diffusion tensor imaging improves the accuracy and sensitivity of white matter analysis in Alzheimer's disease. Sci Rep. 2021; 11(1):6990. PMC: 7998032. DOI: 10.1038/s41598-021-86505-7. View

18.

Li X, Li T, Andreasen N, Wiberg M, Westman E, Wahlund L . The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer's disease. J Intern Med. 2013; 275(4):418-27. DOI: 10.1111/joim.12164. View

19.

Maillard P, Lu H, Arfanakis K, Gold B, Bauer C, Zachariou V . Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits. Alzheimers Dement (Amst). 2022; 14(1):e12261. PMC: 8959640. DOI: 10.1002/dad2.12261. View

20.

Mayer C, Nagele F, Petersen M, Frey B, Hanning U, Pasternak O . Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease. J Cereb Blood Flow Metab. 2022; 42(9):1707-1718. PMC: 9441727. DOI: 10.1177/0271678X221093579. View