Leveraging Longitudinal Diffusion MRI Data to Quantify Differences in White Matter Microstructural Decline in Normal and Abnormal Aging

Overview

Journal Alzheimers Dement (Amst)

Date 2023 Oct 2

PMID 37780863

Authors

Derek B Archer

Kurt Schilling

Niranjana Shashikumar

Varuna Jasodanand

Elizabeth E Moore

Kimberly R Pechman

Murat Bilgel

Lori L Beason-Held

Yang An

Andrea Shafer

Luigi Ferrucci

Shannon L Risacher

Katherine A Gifford

Bennett A Landman

Angela L Jefferson

Andrew J Saykin

Susan M Resnick

Timothy J Hohman

Affiliations

Soon will be listed here.

Abstract

Introduction: It is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging.

Methods: Diffusion MRI data from several well-established longitudinal cohorts of aging (Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], Vanderbilt Memory & Aging Project [VMAP]) were free-water corrected and harmonized. This dataset included 1723 participants (age at baseline: 72.8 ± 8.87 years, 49.5% male) and 4605 imaging sessions (follow-up time: 2.97 ± 2.09 years, follow-up range: 1-13 years, mean number of visits: 4.42 ± 1.98). Differences in white matter microstructural decline in normal and abnormal agers was assessed.

Results: While we found a global decline in white matter in normal/abnormal aging, we found that several white matter tracts (e.g., cingulum bundle) were vulnerable to abnormal aging.

Conclusions: There is a prevalent role of white matter microstructural decline in aging, and future large-scale studies in this area may further refine our understanding of the underlying neurodegenerative processes.

Highlights: Longitudinal data were free-water corrected and harmonized.Global effects of white matter decline were seen in normal and abnormal aging.The free-water metric was most vulnerable to abnormal aging.Cingulum free-water was the most vulnerable to abnormal aging.

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References

Archer D, Vaillancourt D, Coombes S . A Template and Probabilistic Atlas of the Human Sensorimotor Tracts using Diffusion MRI. Cereb Cortex. 2017; 28(5):1685-1699. PMC: 5907352. DOI: 10.1093/cercor/bhx066. View

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

Lovden M, Jonsson Laukka E, Rieckmann A, Kalpouzos G, Li T, Jonsson T . The dimensionality of between-person differences in white matter microstructure in old age. Hum Brain Mapp. 2012; 34(6):1386-98. PMC: 6870246. DOI: 10.1002/hbm.21518. View

Brickman A, Meier I, Korgaonkar M, Provenzano F, Grieve S, Siedlecki K . Testing the white matter retrogenesis hypothesis of cognitive aging. Neurobiol Aging. 2011; 33(8):1699-715. PMC: 3222729. DOI: 10.1016/j.neurobiolaging.2011.06.001. View

Avants B, Epstein C, Grossman M, Gee J . Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal. 2007; 12(1):26-41. PMC: 2276735. DOI: 10.1016/j.media.2007.06.004. View

Sexton C, Kalu U, Filippini N, Mackay C, Ebmeier K . A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2010; 32(12):2322.e5-18. DOI: 10.1016/j.neurobiolaging.2010.05.019. View

Carreira Figueiredo I, Borgan F, Pasternak O, Turkheimer F, Howes O . White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology. 2022; 47(7):1413-1420. PMC: 9117206. DOI: 10.1038/s41386-022-01272-x. View

Archer D, Schilling K, Shashikumar N, Jasodanand V, Moore E, Pechman K . Leveraging longitudinal diffusion MRI data to quantify differences in white matter microstructural decline in normal and abnormal aging. Alzheimers Dement (Amst). 2023; 15(4):e12468. PMC: 10540270. DOI: 10.1002/dad2.12468. View

Mori S, Oishi K, Jiang H, Jiang L, Li X, Akhter K . Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage. 2008; 40(2):570-582. PMC: 2478641. DOI: 10.1016/j.neuroimage.2007.12.035. View

10.

Berlot R, Metzler-Baddeley C, Jones D, OSullivan M . CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment. Neuroimage. 2014; 92:27-35. PMC: 4010672. DOI: 10.1016/j.neuroimage.2014.01.031. View

11.

Bennett I, Madden D, Vaidya C, Howard D, Howard Jr J . Age-related differences in multiple measures of white matter integrity: A diffusion tensor imaging study of healthy aging. Hum Brain Mapp. 2009; 31(3):378-90. PMC: 2826569. DOI: 10.1002/hbm.20872. View

12.

Burciu R, Ofori E, Archer D, Wu S, Pasternak O, McFarland N . Progression marker of Parkinson's disease: a 4-year multi-site imaging study. Brain. 2017; 140(8):2183-2192. PMC: 6057495. DOI: 10.1093/brain/awx146. View

13.

Bender A, Raz N . Normal-appearing cerebral white matter in healthy adults: mean change over 2 years and individual differences in change. Neurobiol Aging. 2015; 36(5):1834-48. PMC: 4419147. DOI: 10.1016/j.neurobiolaging.2015.02.001. View

14.

Archer D, Moore E, Pamidimukkala U, Shashikumar N, Pechman K, Blennow K . The relationship between white matter microstructure and self-perceived cognitive decline. Neuroimage Clin. 2021; 32:102794. PMC: 8414539. DOI: 10.1016/j.nicl.2021.102794. View

15.

Bozzali M, Giulietti G, Basile B, Serra L, Spano B, Perri R . Damage to the cingulum contributes to Alzheimer's disease pathophysiology by deafferentation mechanism. Hum Brain Mapp. 2011; 33(6):1295-308. PMC: 6870125. DOI: 10.1002/hbm.21287. View

16.

Shafer A, Williams O, Perez E, An Y, Landman B, Ferrucci L . Accelerated decline in white matter microstructure in subsequently impaired older adults and its relationship with cognitive decline. Brain Commun. 2022; 4(2):fcac051. PMC: 8963308. DOI: 10.1093/braincomms/fcac051. View

17.

Chad J, Pasternak O, Salat D, Chen J . Re-examining age-related differences in white matter microstructure with free-water corrected diffusion tensor imaging. Neurobiol Aging. 2018; 71:161-170. PMC: 6179151. DOI: 10.1016/j.neurobiolaging.2018.07.018. View

18.

Beer J, Tustison N, Cook P, Davatzikos C, Sheline Y, Shinohara R . Longitudinal ComBat: A method for harmonizing longitudinal multi-scanner imaging data. Neuroimage. 2020; 220:117129. PMC: 7605103. DOI: 10.1016/j.neuroimage.2020.117129. View

19.

Bartzokis G, Sultzer D, Lu P, Nuechterlein K, Mintz J, Cummings J . Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical "disconnection" in aging and Alzheimer's disease. Neurobiol Aging. 2004; 25(7):843-51. DOI: 10.1016/j.neurobiolaging.2003.09.005. View

20.

Davis S, Dennis N, Buchler N, White L, Madden D, Cabeza R . Assessing the effects of age on long white matter tracts using diffusion tensor tractography. Neuroimage. 2009; 46(2):530-41. PMC: 2775533. DOI: 10.1016/j.neuroimage.2009.01.068. View