Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)

Nicholas M. Pajewski; Fanny M. Elahi; Manjula Kurella Tamura; Jason D. Hinman; Ilya M. Nasrallah; Joachim H. Ix; Lindsay M. Miller; Lenore J. Launer; Clinton B. Wright; Mark A. Supiano; Alan J. Lerner; Tiffany L. Sudduth; Anthony A. Killeen; Alfred K. Cheung; David M. Reboussin; Donna M. Wilcock; Jeff D. Williamson

doi:10.1002/alz.12496

Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)

Nicholas M. Pajewski, Fanny M. Elahi, Manjula Kurella Tamura, Jason D. Hinman, Ilya M. Nasrallah, Joachim H. Ix, Lindsay M. Miller, Lenore J. Launer, Clinton B. Wright, Mark A. Supiano, Alan J. Lerner, Tiffany L. Sudduth, Anthony A. Killeen, Alfred K. Cheung, David M. Reboussin, Donna M. Wilcock, Jeff D. Williamson

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Introduction: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. Methods: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aβ)₄₀ and Aβ₄₂, total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517). Results: Over 3.8 years, there were no significant between-group differences for Aβ_40, Aβ_42, Aβ₄₂/Aβ_40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL. Discussion: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01206062.

Original language	English
Pages (from-to)	1472-1483
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	18
Issue number	8
DOIs	https://doi.org/10.1002/alz.12496
State	Published - Aug 2022
Externally published	Yes

Keywords

biomarkers
blood pressure
cognitive dysfunction
dementia
hypertension
plasma

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10.1002/alz.12496

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Pajewski, N. M., Elahi, F. M., Tamura, M. K., Hinman, J. D., Nasrallah, I. M., Ix, J. H., Miller, L. M., Launer, L. J., Wright, C. B., Supiano, M. A., Lerner, A. J., Sudduth, T. L., Killeen, A. A., Cheung, A. K., Reboussin, D. M., Wilcock, D. M., & Williamson, J. D. (2022). Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT). Alzheimer's and Dementia, 18(8), 1472-1483. https://doi.org/10.1002/alz.12496

@article{95ad6e649203417ba452ff5bffca91a2,

title = "Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)",

abstract = "Introduction: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. Methods: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aβ)40 and Aβ42, total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517). Results: Over 3.8 years, there were no significant between-group differences for Aβ40, Aβ42, Aβ42/Aβ40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL. Discussion: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01206062.",

keywords = "biomarkers, blood pressure, cognitive dysfunction, dementia, hypertension, plasma",

author = "Pajewski, {Nicholas M.} and Elahi, {Fanny M.} and Tamura, {Manjula Kurella} and Hinman, {Jason D.} and Nasrallah, {Ilya M.} and Ix, {Joachim H.} and Miller, {Lindsay M.} and Launer, {Lenore J.} and Wright, {Clinton B.} and Supiano, {Mark A.} and Lerner, {Alan J.} and Sudduth, {Tiffany L.} and Killeen, {Anthony A.} and Cheung, {Alfred K.} and Reboussin, {David M.} and Wilcock, {Donna M.} and Williamson, {Jeff D.}",

note = "Funding Information: N. M. Pajewski has received funding from the NIA, NHLBI, NIDDK, and the Duke Endowment; and is serving on Data and Safety Monitoring Boards (DSMBs) for the NIA and National Institute of Nursing Research (unpaid). F. M. Elahi is the vice chair of the vascular cognitive disorders Professional Interest Area of ISTAART. M. Kurella Tamura is supported by R01DK092241, serves on DSMBs for NIDDK and the VA (unpaid), and serves on advisory boards for the Clinician–Scientists Transdisciplinary Aging Research Coordinating Center (Clin‐STAR) and Paul B. Beeson Emerging Leaders Career Development Award in Aging, for which she receives an honorarium from the American Federation of Aging Research. J. D. Hinman is supported by UH3NS100608; receives funding from the NIA, NINDS, American Heart Association, and American Neurological Association; has provided expert testimony for Bertoldo Baker Carter & Smith, Federal Public Defender–Central District of California, Popham Law Firm, WarrenAllen, LLP, Robert Miller Attorney at Law, Kjar McKenna & Stockalper, LLP, Matthew Millea Attorney at Law, Koskoff Koskoff & Bieder PC, and Goodwin Law; owns stock in Sage Cerebrovascular Diagnostics; and his institution has received drugs from Constant Therapeutics. I. M. Nasrallah receives funding from the NIH and the American Society of Neuroradiology; and has served as an educational speaker for Biogen. J. H. Ix receives funding from the NIDDK; has received consulting fees from AstraZeneca, Jnana Pharmaceuticals, and Ardelyx Pharmaceuticals; has received speaking honorarium from the National Kidney Foundation; serves on a DSMB for Sanifit International; serves on the Scientific Advisory Board for AlphaYoung; and has received donated study drug from Genentech Pharmaceuticals unrelated to the present work. L. M. Miller was supported by T32DK104717. L. J. Launer has nothing to disclose. C. B. Wright has received royalties from UpToDate.com. M. A. Supiano is supported by R01AG055606; has received textbook royalties from McGraw‐Hill; serves on a DSMB for the Depressed MIND study (unpaid); and serves on the board of the American Geriatrics Society. A. J. Lerner has received funding from Premier Applied Biosciences and the Elizabeth Prentiss Foundation; has received book royalty payments from Elsevier; and has received speaking honorarium from the Puerto Rican Academy of Neurology. T. L. Sudduth has nothing to disclose. A. A. Killeen has received funding from the NIDDK, Centers for Disease Control and Prevention, Diasorin, Inc., and ARKRAY Inc.; has received book royalty payments from Elsevier; has received consulting fees from the American Association for Clinical Chemistry; has held leadership roles for the American Association for Clinical Chemistry, College of American Pathologists, and the Academy of Clinical Laboratory Physicians and Scientists; and has received laboratory reagents from Roche Diagnostics for research studies unrelated to the present work. A. K. Cheung has received funding from the NIH; has received royalty payments from UpToDate.com; and has received consulting fees from Boehringer‐Ingelheim and Calliditas. D. M. Reboussin is supported by R01AG055606; has received funding from the Alzheimer's Association and the NIH; and serves on DSMBs for the NIH (unpaid). D. M. Wilcock is supported by UH3NS100606; receives funding from the NIA and NINDS; has received consulting fees from Alector and AC Immune and honoraria from the Neuroscience Education Institute, University of California Irvine, Louisiana State University‐Shreveport; and has received travel support from the Alzheimer's Association, Alzheimer's and Parkinson's Diseases Conference, and the Brightfocus Foundation. J. D. Williamson is supported by R01AG055606; has received funding from the NIH; and serves on DSMBs for the China National Center for Cardiovascular Diseases and the NIH (unpaid). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Alzheimer's Association, National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. Funding Information: Funding for this project was provided by the Alzheimer's Association. The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Institute on Aging (NIA); and the National Institute of Neurological Disorders and Stroke (NINDS) under contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A‐HL‐13‐002‐001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs (VA). Azilsartan and chlorthalidone (combined with azilsartan) were provided by Takeda Pharmaceuticals International Inc. Additional support was provided through the following National Center for Advancing Translational Sciences clinical and translational science awards: UL1TR000439 (awarded to Case Western Reserve University); UL1RR025755 (Ohio State University); UL1RR024134 and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston University); UL1TR000093 (Stanford University); UL1RR025752, UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017‐06 (University of Texas Southwestern Medical Center); UL1TR000105‐05 (University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075 (George Washington University); UL1 TR000002 (University of California, Davis); UL1 TR000064 (University of Florida); and UL1TR000433 (University of Michigan); and by National Institute of General Medical Sciences, Centers of Biomedical Research Excellence award NIGMS P30GM103337 (awarded to Tulane University. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association.",

year = "2022",

month = aug,

doi = "10.1002/alz.12496",

language = "English",

volume = "18",

pages = "1472--1483",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley & Sons Inc.",

number = "8",

}

Pajewski, NM, Elahi, FM, Tamura, MK, Hinman, JD, Nasrallah, IM, Ix, JH, Miller, LM, Launer, LJ, Wright, CB, Supiano, MA, Lerner, AJ, Sudduth, TL, Killeen, AA, Cheung, AK, Reboussin, DM, Wilcock, DM & Williamson, JD 2022, 'Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)', Alzheimer's and Dementia, vol. 18, no. 8, pp. 1472-1483. https://doi.org/10.1002/alz.12496

TY - JOUR

T1 - Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)

AU - Pajewski, Nicholas M.

AU - Elahi, Fanny M.

AU - Tamura, Manjula Kurella

AU - Hinman, Jason D.

AU - Nasrallah, Ilya M.

AU - Ix, Joachim H.

AU - Miller, Lindsay M.

AU - Launer, Lenore J.

AU - Wright, Clinton B.

AU - Supiano, Mark A.

AU - Lerner, Alan J.

AU - Sudduth, Tiffany L.

AU - Killeen, Anthony A.

AU - Cheung, Alfred K.

AU - Reboussin, David M.

AU - Wilcock, Donna M.

AU - Williamson, Jeff D.

N1 - Funding Information: N. M. Pajewski has received funding from the NIA, NHLBI, NIDDK, and the Duke Endowment; and is serving on Data and Safety Monitoring Boards (DSMBs) for the NIA and National Institute of Nursing Research (unpaid). F. M. Elahi is the vice chair of the vascular cognitive disorders Professional Interest Area of ISTAART. M. Kurella Tamura is supported by R01DK092241, serves on DSMBs for NIDDK and the VA (unpaid), and serves on advisory boards for the Clinician–Scientists Transdisciplinary Aging Research Coordinating Center (Clin‐STAR) and Paul B. Beeson Emerging Leaders Career Development Award in Aging, for which she receives an honorarium from the American Federation of Aging Research. J. D. Hinman is supported by UH3NS100608; receives funding from the NIA, NINDS, American Heart Association, and American Neurological Association; has provided expert testimony for Bertoldo Baker Carter & Smith, Federal Public Defender–Central District of California, Popham Law Firm, WarrenAllen, LLP, Robert Miller Attorney at Law, Kjar McKenna & Stockalper, LLP, Matthew Millea Attorney at Law, Koskoff Koskoff & Bieder PC, and Goodwin Law; owns stock in Sage Cerebrovascular Diagnostics; and his institution has received drugs from Constant Therapeutics. I. M. Nasrallah receives funding from the NIH and the American Society of Neuroradiology; and has served as an educational speaker for Biogen. J. H. Ix receives funding from the NIDDK; has received consulting fees from AstraZeneca, Jnana Pharmaceuticals, and Ardelyx Pharmaceuticals; has received speaking honorarium from the National Kidney Foundation; serves on a DSMB for Sanifit International; serves on the Scientific Advisory Board for AlphaYoung; and has received donated study drug from Genentech Pharmaceuticals unrelated to the present work. L. M. Miller was supported by T32DK104717. L. J. Launer has nothing to disclose. C. B. Wright has received royalties from UpToDate.com. M. A. Supiano is supported by R01AG055606; has received textbook royalties from McGraw‐Hill; serves on a DSMB for the Depressed MIND study (unpaid); and serves on the board of the American Geriatrics Society. A. J. Lerner has received funding from Premier Applied Biosciences and the Elizabeth Prentiss Foundation; has received book royalty payments from Elsevier; and has received speaking honorarium from the Puerto Rican Academy of Neurology. T. L. Sudduth has nothing to disclose. A. A. Killeen has received funding from the NIDDK, Centers for Disease Control and Prevention, Diasorin, Inc., and ARKRAY Inc.; has received book royalty payments from Elsevier; has received consulting fees from the American Association for Clinical Chemistry; has held leadership roles for the American Association for Clinical Chemistry, College of American Pathologists, and the Academy of Clinical Laboratory Physicians and Scientists; and has received laboratory reagents from Roche Diagnostics for research studies unrelated to the present work. A. K. Cheung has received funding from the NIH; has received royalty payments from UpToDate.com; and has received consulting fees from Boehringer‐Ingelheim and Calliditas. D. M. Reboussin is supported by R01AG055606; has received funding from the Alzheimer's Association and the NIH; and serves on DSMBs for the NIH (unpaid). D. M. Wilcock is supported by UH3NS100606; receives funding from the NIA and NINDS; has received consulting fees from Alector and AC Immune and honoraria from the Neuroscience Education Institute, University of California Irvine, Louisiana State University‐Shreveport; and has received travel support from the Alzheimer's Association, Alzheimer's and Parkinson's Diseases Conference, and the Brightfocus Foundation. J. D. Williamson is supported by R01AG055606; has received funding from the NIH; and serves on DSMBs for the China National Center for Cardiovascular Diseases and the NIH (unpaid). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Alzheimer's Association, National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. Funding Information: Funding for this project was provided by the Alzheimer's Association. The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Institute on Aging (NIA); and the National Institute of Neurological Disorders and Stroke (NINDS) under contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A‐HL‐13‐002‐001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs (VA). Azilsartan and chlorthalidone (combined with azilsartan) were provided by Takeda Pharmaceuticals International Inc. Additional support was provided through the following National Center for Advancing Translational Sciences clinical and translational science awards: UL1TR000439 (awarded to Case Western Reserve University); UL1RR025755 (Ohio State University); UL1RR024134 and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston University); UL1TR000093 (Stanford University); UL1RR025752, UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017‐06 (University of Texas Southwestern Medical Center); UL1TR000105‐05 (University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075 (George Washington University); UL1 TR000002 (University of California, Davis); UL1 TR000064 (University of Florida); and UL1TR000433 (University of Michigan); and by National Institute of General Medical Sciences, Centers of Biomedical Research Excellence award NIGMS P30GM103337 (awarded to Tulane University. Publisher Copyright: © 2021 the Alzheimer's Association.

PY - 2022/8

Y1 - 2022/8

N2 - Introduction: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. Methods: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aβ)40 and Aβ42, total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517). Results: Over 3.8 years, there were no significant between-group differences for Aβ40, Aβ42, Aβ42/Aβ40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL. Discussion: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01206062.

AB - Introduction: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. Methods: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aβ)40 and Aβ42, total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517). Results: Over 3.8 years, there were no significant between-group differences for Aβ40, Aβ42, Aβ42/Aβ40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL. Discussion: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01206062.

KW - biomarkers

KW - blood pressure

KW - cognitive dysfunction

KW - dementia

KW - hypertension

KW - plasma

UR - http://www.scopus.com/inward/record.url?scp=85119055419&partnerID=8YFLogxK

U2 - 10.1002/alz.12496

DO - 10.1002/alz.12496

M3 - Article

C2 - 34786815

AN - SCOPUS:85119055419

SN - 1552-5260

VL - 18

SP - 1472

EP - 1483

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 8

ER -

Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)

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