Vascular burden and Alzheimer disease pathologic progression
Open accessAbstract
OBJECTIVE: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS: Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.
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In the Alzheimer Disease Neuroimaging Initiative, no interactions were noted between vascular risk factors and AD biomarkers.
“Modern CSF biomarkers may support a direct relationship between SVD and AD pathology [195], although in the Alzheimer Disease Neuroimaging Initiative that is focused on AD, no interactions were noted between vascular risk factors and AD biomarkers [26].”
From The overlap between vascular disease and Alzheimer’s disease - lessons from pathology (2014) · cites this paper as [26]
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Vascular risk burden is a key player in the early progression of Alzheimer’s disease
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Self-citationPathogenesis and Treatment of Vascular Cognitive Impairment
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Mixed Brain Pathology Is the Most Common Cause of Cognitive Impairment in the Elderly
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An Overview of Experimental and Clinical Spinal Cord Findings in Alzheimer’s Disease
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The Impact of Amyloid-β or Tau on Cognitive Change in the Presence of Severe Cerebrovascular Disease
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Self-citationTHE EFFECT OF VASCULAR NEUROPATHOLOGY ON LATE-LIFE COGNITION: RESULTS FROM THE SMART PROJECT
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Self-citationIntravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study
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Independent value added by diffusion MRI for prediction of cognitive function in older adults
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White Matter Hyperintensities in Mild Cognitive Impairment and Lower Risk of Cognitive Decline
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Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
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Longitudinal associations of cardiovascular health and vascular events with incident dementia
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- Authors
- Lo, R. Y., Jagust, W. J., Weiner, M., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Liu, E., Green, R. C., Montine, T., Petersen, R., Aisen, P., Gamst, A., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Beckett, L., Harvey, D., Gamst, A., Donohue, M., Kornak, J., Jack, C. R., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., DeCarli, C., Jagust, W., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Morris, J., Cairns, N. J., Taylor-Reinwald, L., Trojanowki, J. Q., Shaw, L., Lee, V. M. Y., Korecka, M., Toga, A. W., Crawford, K., Neu, S., Saykin, A. J., Foroud, T. M., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, L. S., Pawluczyk, S., Spann, B. M., Brewer, J., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Petersen, R., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, L. S., Bell, K. L., Morris, J. C., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Coleman, R. E., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Lu, P. H., Bartzokis, G., Silverman, D. H. S., Graff-Radford, N. R., Parfitt, F., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, D. B., Caldwell, C., Hsiung, G.-Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, M.-M., Lipowski, K., Wu, C.-K., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Bwayo, S. K., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., DeCarli, C., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, D. R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Saykin, A. J., Santulli, R. B., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Longmire, C. F., Spicer, K., Finger, E., Rachinsky, I., Rogers, J., Kertesz, A., & Drost, D.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- From the Division of Epidemiology, School of Public Health (R.Y.L., W.J.J.), and Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; Department of Neurology (R.Y.L.), Buddhist Tzu Chi General Hospital, Hualien, Taiwan; College of Medicine (R.Y.L.), Tzu Chi University, Hualien, Taiwan; and Life Sciences Division (W.J.J.), Lawrence Berkeley National Laboratory, Berkeley, CA.
- U Pennsylvania
- Janssen Alzheimer Immunotherapy
- University of Washington (US)
- University of California San Diego (US)
- University of California, Davis (US)
- Mayo Clinic, Rochester
- Mayo Clinic (US)
- University of London (GB)
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- Banner Alzheimer’s Institute (US)
- University of Michigan (US)
- University of Utah (US)
- University of Pittsburgh
- Washington University in St. Louis (US)
- Washington University St. Louis
- UPenn School of Medicine (Core PI)
- University of Pennsylvania (US)
- Indiana University (US)
- UC Irvine
- Buddhist Tzu Chi General Hospital (TW)
- Alzheimer's Association (US)
- General Electric (United States) (US)
- University of Connecticut (US)
- National Institutes of Health (US)
- Oregon Health & Science University (US)
- University of Southern California (US)
- Brigham and Women's Hospital (US)
- Baylor College of Medicine (US)
- Baylor College of Medicine
- Columbia University Irving Medical Center (US)
- Washington University, St. Louis
- University of Alabama at Birmingham (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rush University Medical Center
- Rush University Medical Center (US)
- Wein Center
- Johns Hopkins University (US)
- New York University (US)
- New York University
- Duke Medical Center (US)
- University of Kentucky (US)
- University of Kentucky
- University of Pittsburgh (US)
- University of Rochester Medicine (US)
- University of California, Irvine (US)
- The University of Texas Southwestern Medical Center (US)
- Emory University (US)
- University of Kansas Medical Center (US)
- Mayo Clinic, Jacksonville
- Mayo Clinic in Florida (US)
- Yale University School of Medicine
- Yale University (US)
- Jewish General Hospital (CA)
- Sunnybrook Health Science Centre (CA)
- Sunnybrook Health Sciences, Ontario
- U.B.C. Clinic for AD & Related Disorders
- Cognitive Neurology - St. Joseph's, Ontario
- Cleveland Clinic (US)
- Northwestern University (US)
- Northwestern University
- Palm Beach Neurology (US)
- Premiere Research Inst (Palm Beach Neurology)
- Georgetown University Medical Center (US)
- Stanford University (US)
- Banner Sun Health Research Institute (US)
- Boston University (US)
- Howard University (US)
- Case Western Reserve University (US)
- Neurological Care of CNY
- Parkwood Hospital
- University of Wisconsin System (US)
- University of California, Irvine - BIC
- Dent Neurologic Institute (US)
- The Ohio State University (US)
- Albany Medical College (US)
- Hartford Hospital (US)
- Dartmouth–Hitchcock Medical Center (US)
- Wake Forest University Health Sciences (US)
- Rhode Island Hospital (US)
- Butler Hospital (US)
- Medical University of South Carolina (US)
- St. Joseph's Health Care
- ORCID
- Lo, Raymond Y.
- Liu, Enchi
- Thomas, Ronald G.
- Walter, Sarah
- Harvey, Danielle
- Kornak, John
- Dale, Anders
- Felmlee, Joel
- Fox, Nick
- Thompson, Paul
- Koeppe, Robert A.
- Reiman, Eric M.
- Chen, Kewei
- Lee, Virginia M.Y.
- Korecka, Magdalena
- Crawford, Karen
- Foroud, Tatiana M.
- Shen, Li
- Frank, Richard
- Snyder, Peter J.
- Kaye, Jeffrey
- Schneider, Lon S.
- Heidebrink, Judith L.
- Lord, Joanne L.
- Johnson, Kris
- Stern, Yaakov
- Honig, Lawrence S.
- Bell, Karen L.
- Ances, Beau
- Carroll, Maria
- Marson, Daniel
- Clark, David
- Shah, Raj C.
- Duara, Ranjan
- Albert, Marilyn
- Kielb, Stephanie
- Rusinek, Henry
- Glodzik, Lidia
- Doraiswamy, P. Murali
- Petrella, Jeffrey R.
- Arnold, Steven E.
- Karlawish, Jason H.
- Wolk, David
- Smith, Charles D.
- Hardy, Peter
- Porsteinsson, Anton P.
- Ismail, M. Saleem
- Thai, Gaby
- Womack, Kyle
- Quiceno, Mary
- Diaz-Arrastia, Ramon
- Weiner, Myron
- DeVous, Michael
- Levey, Allan I.
- Lah, James J.
- Burns, Jeffrey M.
- Swerdlow, Russell H.
- Apostolova, Liana
- Lu, Po H.
- Silverman, Daniel H.S.
- Johnson, Heather
- Farlow, Martin R.
- Hake, Ann Marie
- Carson, Richard E.
- Chertkow, Howard
- Bergman, Howard
- Hsiung, Ging-Yuek Robin
- Feldman, Howard
- Bernick, Charles
- Kerwin, Diana
- Johnson, Nancy
- Turner, Raymond Scott
- Sperling, Reisa A.
- Johnson, Keith A.
- Marshall, Gad
- Frey, Meghan
- Yesavage, Jerome
- Taylor, Joy L.
- Lane, Barton
- Rosen, Allyson
- Sabbagh, Marwan
- Belden, Christine
- Jacobson, Sandra
- Kowall, Neil
- Killiany, Ronald
- Budson, Andrew E.
- Norbash, Alexander
- Obisesan, Thomas O.
- Lerner, Alan
- Carmichael, Owen
- Olichney, John
- Johnson, Sterling
- Asthana, Sanjay
- Carlsson, Cynthia M.
- Preda, Adrian
- Nguyen, Dana
- Tariot, Pierre
- Fleisher, Adam
- Scharre, Douglas W.
- Kataki, Maria
- Pearlson, Godfrey D.
- Santulli, Robert B.
- Sink, Kaycee M.
- Williamson, Jeff D.
- Garg, Pradeep
- Ott, Brian R.
- Tremont, Geoffrey
- Salloway, Stephen
- Correia, Stephen
- Rosen, Howard J.
- Miller, Bruce L.
- Mintzer, Jacobo
- Venue
- Neurology
- Published
- 2012-09-25
- Volume
- 79
- Issue
- 13
- Pages
- 1349-1355
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3448744
- OpenAlex
- W2055568131
- Cited by
- 156
- References
- 36
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 12 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 18 · 2015: 25 · 2014: 24 · 2013: 13
- FWCI
- 14.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514, P30AG013846, U19AG010483)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- Alzheimer's disease, vascular burden, white matter hyperintensities, cardiovascular risk, mild cognitive impairment, CSF amyloid-beta 42, hippocampal atrophy, executive function decline, APOE ε4, disease progression
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Brain, Female, Genotype, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Disease Progression, Positron-Emission Tomography, Leukoencephalopathies, Cognitive Dysfunction
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