MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts
This is the first study to investigate the mediation role of interstitial FW fraction (WM-FW) on the relationship between glymphatic clearance (ALPS index) and EF (UDS3-EF scores) in four independent middle to aged cohorts at risk for cSVD. This study identified that ALPS index was independently associated with UDS3-EF scores after adjusting for demographics, VRFs, and WM hyperintensity burden and that WM-FW mediated this association in all middle to aged cohorts. Our findings suggest that in middle to aged individuals, glymphatic dysfunction (reflected by ALPS index) is strongly associated with EF and that this association is mediated by the ISF drainage in WM. This study provides a strong clinical rationale for the use of the ALPS index as a marker of cognitive function in multi-site observational studies and clinical trials to monitor and prevent VCID.
Authors
- Brian T. Gold (ORCID: https://orcid.org/0000-0002-6958-7095)
- Sudha S. Seshadri (ORCID: https://orcid.org/0000-0001-6135-2622)
- Steven Cen (ORCID: https://orcid.org/0000-0002-7859-8909)
- Mohamad Habes (ORCID: https://orcid.org/0000-0001-9447-5805)
- Joel H. Kramer (ORCID: https://orcid.org/0000-0002-2917-8297)
- Lara Stables
- Arvind Caprihan (ORCID: https://orcid.org/0000-0002-4810-359X)
- Xingfeng Shao (ORCID: https://orcid.org/0000-0002-4130-6204)
- Giuseppe Barisano (ORCID: https://orcid.org/0000-0001-5598-1369)
- Kay Jann (ORCID: https://orcid.org/0000-0003-3574-0538)
- Konstantinos Arfanakis (ORCID: https://orcid.org/0000-0001-9705-597X)
- Pauline Maillard (ORCID: https://orcid.org/0000-0003-3516-6345)
- Steven Mark Greenberg (ORCID: https://orcid.org/0000-0003-1792-8887)
- Danny J.J. Wang (ORCID: https://orcid.org/0000-0002-0840-7062)
- Charles DeCarli (ORCID: https://orcid.org/0000-0003-1914-2693)
- Herpreet Singh (ORCID: https://orcid.org/0000-0003-3797-7301)
- John M. Ringman (ORCID: https://orcid.org/0000-0001-5429-0777)
- Xiaodan Liu (ORCID: https://orcid.org/0000-0001-9112-1032)
- Claudia L. Satizábal (ORCID: https://orcid.org/0000-0002-1115-4430)
- Hanzhang Lu
- Karl Helmer
- Alexa S. Beiser
Institutions
- Boston University (US)
- University of Southern California (US)
- Rush University Medical Center (US)
- Mind Research Network (US)
- Harvard University (US)
- University of Kentucky (US)
- Johns Hopkins University (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of California, San Francisco (US)
- Illinois Institute of Technology (US)
- Johns Hopkins Medicine (US)
- University of California System (US)
- Massachusetts General Hospital (US)
- Institute for Neurodegenerative Disorders (US)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Massachusetts Institute of Technology (US)
- University of California, Davis (US)
- Stanford University (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1002/alz.14453
- Citations
- 18
- Primary Topic
- Cerebrospinal fluid and hydrocephalus
- Type
- article
- Field-Weighted Citation Impact
- 4.83
Funders
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke