Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective (2024)

Elahi, F. M., Alladi, S., Black, S. E., Claassen, J. A. H. R., DeCarli, C., Hughes, T. M., Moonen, J., Pajewski, N. M., Price, B. R., Satizabal, C., Shaaban, C. E., Silva, N. R. C. B. S., Snyder, H. M., Sveikata, L., Williamson, J. D., Wolters, F. J., & Hainsworth, A. H. (2023). Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective. Cell Reports Medicine, 4(6), Article 101089. https://doi.org/10.1016/j.xcrm.2023.101089

Elahi, Fanny M. ; Alladi, Suvarna ; Black, Sandra E. et al. / Clinical trials in vascular cognitive impairment following SPRINT-MIND : An international perspective. In: Cell Reports Medicine. 2023 ; Vol. 4, No. 6.

@article{63d27d275dae47e0a8ff4c0abdcd0529,

title = "Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective",

abstract = "A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.",

keywords = "aging, blood pressure, clinical trials, cognitive impairment, dementia, hypertension, prevention, vascular disease",

author = "Elahi, {Fanny M.} and Suvarna Alladi and Black, {Sandra E.} and Claassen, {Jurgen A. H. R.} and Charles DeCarli and Hughes, {Timothy M.} and Justine Moonen and Pajewski, {Nicholas M.} and Price, {Brittani R.} and Claudia Satizabal and Shaaban, {C. Elizabeth} and Silva, {N. rlon C. B. S.} and Snyder, {Heather M.} and Lukas Sveikata and Williamson, {Jeff D.} and Wolters, {Frank J.} and Hainsworth, {Atticus H.}",

note = "Funding Information: All authors are members of The Alzheimer{\textquoteright}s Association International Society to Advance Alzheimer{\textquoteright}s Research and Treatment (ISTAART). This perspective arose from a Roundtable discussion on 20/09/2021, hosted by the Vascular Cognitive Disorders Professional Interest Area within ISTAART. F.M.E. serves on the Scientific Advisory Board of Cordance Medical. S.E.B. has been an ad hoc consultant to Hoffman-LaRoche and Biogen and has participated in educational programs sponsored by Biogen. J.C. is Honorary Visiting Professor in the Department of Cardiovascular Sciences, University of Leicester, UK. C.D. advises Novartis on a safety trial of heart failure treatment and Nova Nordisk on two trials of GLP1 agonist treatment in AD. N.M.P. was a named investigator on the SPRINT-MIND study. B.R.P. is a full-time employee of Life Molecular Imaging Inc. N.C.B.S.S. is a post-doctoral fellow jointly funded by the Michael Smith Health Research BC, the Canadians for Leading Alzheimer Research, and the Canadian Institutes of Health Research. H.M.S. is a full-time employee of the Alzheimer{\textquoteright}s Association. J.D.W. was a named investigator on the SPRINT-MIND study. A.H.H. has received honoraria from Eli-Lilly and from NIA, and chairs the Dementias Platform UK Vascular Experimental Medicine group. Funding Information: Research in F.M.E.{\textquoteright}s group is supported by National Institute on Aging and Department of Veterans Affairs (IK2CX002180), a Larry L. Hillblom start-up grant (2019A012SUP), and an American Academy of Neurology fellowship. J.M. is appointed at the Netherlands Consortium of Dementia Cohorts (NCDC), which is funded in the context of Deltaplan Dementie from ZonMW Memorabel (project nr 73305095005) and Alzheimer Nederland. C.D. is supported by NIH P30 AG 072972 U19 NS 120384, and UF1NS100608. N.M.P. is supported by R01 AG055606 and R01 AG065805 from the National Institute on Aging. L.S. was supported by a Swiss National Science Foundation award [P2GEP3_191584]. C.E.S. was supported by T32 AG055381 and is presently supported by K01AG071849, both from the National Institute on Aging of the US National Institutes of Health. J.D.W. is supported by R01 AG055606 from the National Institute on Aging. F.J.W. is supported by the Alzheimer's Association (AARF-22-924982) and the Netherlands Organisation for Health Research and Development (ZonMw) (Veni 09150162010108). Research in A.H.H.{\textquoteright}s group is funded by the UK Medical Research Council (MR/R005567/1, MR/T033371/1), British Heart Foundation (PG/20/10397), UK Alzheimer's Society, and Alzheimer's Drug Discovery Foundation (20140901). The graphical abstract was prepared using BioRender. The views expressed in this paper are those of the individual authors. Conceptualization, F.M.E. and A.H.H.; ideas, all authors; writing – original draft, A.H.H.; writing – review & editing the final draft, all authors. All authors are members of The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). This perspective arose from a Roundtable discussion on 20/09/2021, hosted by the Vascular Cognitive Disorders Professional Interest Area within ISTAART. F.M.E. serves on the Scientific Advisory Board of Cordance Medical. S.E.B. has been an ad hoc consultant to Hoffman-LaRoche and Biogen and has participated in educational programs sponsored by Biogen. J.C. is Honorary Visiting Professor in the Department of Cardiovascular Sciences, University of Leicester, UK. C.D. advises Novartis on a safety trial of heart failure treatment and Nova Nordisk on two trials of GLP1 agonist treatment in AD. N.M.P. was a named investigator on the SPRINT-MIND study. B.R.P. is a full-time employee of Life Molecular Imaging Inc. N.C.B.S.S. is a post-doctoral fellow jointly funded by the Michael Smith Health Research BC, the Canadians for Leading Alzheimer Research, and the Canadian Institutes of Health Research. H.M.S. is a full-time employee of the Alzheimer's Association. J.D.W. was a named investigator on the SPRINT-MIND study. A.H.H. has received honoraria from Eli-Lilly and from NIA, and chairs the Dementias Platform UK Vascular Experimental Medicine group. One or more of the authors of this paper self-identifies as an under-represented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as living with a disability. Funding Information: Research in F.M.E.{\textquoteright}s group is supported by National Institute on Aging and Department of Veterans Affairs ( IK2CX002180 ), a Larry L. Hillblom start-up grant ( 2019A012SUP ), and an American Academy of Neurology fellowship. J.M. is appointed at the Netherlands Consortium of Dementia Cohorts ( NCDC ), which is funded in the context of Deltaplan Dementie from ZonMW Memorabel (project nr 73305095005) and Alzheimer Nederland . C.D. is supported by NIH P30 AG 072972 U19 NS 120384 , and UF1NS100608 . N.M.P. is supported by R01 AG055606 and R01 AG065805 from the National Institute on Aging . L.S. was supported by a Swiss National Science Foundation award [ P2GEP3_191584 ]. C.E.S. was supported by T32 AG055381 and is presently supported by K01AG071849 , both from the National Institute on Aging of the US National Institutes of Health . J.D.W. is supported by R01 AG055606 from the National Institute on Aging . F.J.W. is supported by the Alzheimer's Association ( AARF-22-924982 ) and the Netherlands Organisation for Health Research and Development ( ZonMw ) (Veni 09150162010108 ). Research in A.H.H.{\textquoteright}s group is funded by the UK Medical Research Council ( MR/R005567/1 , MR/T033371/1 ), British Heart Foundation ( PG/20/10397 ), UK Alzheimer{\textquoteright}s Society , and Alzheimer's Drug Discovery Foundation ( 20140901 ). The graphical abstract was prepared using BioRender. The views expressed in this paper are those of the individual authors. Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = jun,

day = "20",

doi = "https://doi.org/10.1016/j.xcrm.2023.101089",

language = "English",

volume = "4",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

Elahi, FM, Alladi, S, Black, SE, Claassen, JAHR, DeCarli, C, Hughes, TM, Moonen, J, Pajewski, NM, Price, BR, Satizabal, C, Shaaban, CE, Silva, NRCBS, Snyder, HM, Sveikata, L, Williamson, JD, Wolters, FJ & Hainsworth, AH 2023, 'Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective', Cell Reports Medicine, vol. 4, no. 6, 101089. https://doi.org/10.1016/j.xcrm.2023.101089

Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective. / Elahi, Fanny M.; Alladi, Suvarna; Black, Sandra E. et al.
In: Cell Reports Medicine, Vol. 4, No. 6, 101089, 20.06.2023.

Research output: Contribution to journal › Review article › Academic › peer-review

TY - JOUR

T1 - Clinical trials in vascular cognitive impairment following SPRINT-MIND

T2 - An international perspective

AU - Elahi, Fanny M.

AU - Alladi, Suvarna

AU - Black, Sandra E.

AU - Claassen, Jurgen A. H. R.

AU - DeCarli, Charles

AU - Hughes, Timothy M.

AU - Moonen, Justine

AU - Pajewski, Nicholas M.

AU - Price, Brittani R.

AU - Satizabal, Claudia

AU - Shaaban, C. Elizabeth

AU - Silva, N. rlon C. B. S.

AU - Snyder, Heather M.

AU - Sveikata, Lukas

AU - Williamson, Jeff D.

AU - Wolters, Frank J.

AU - Hainsworth, Atticus H.

N1 - Funding Information: All authors are members of The Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART). This perspective arose from a Roundtable discussion on 20/09/2021, hosted by the Vascular Cognitive Disorders Professional Interest Area within ISTAART. F.M.E. serves on the Scientific Advisory Board of Cordance Medical. S.E.B. has been an ad hoc consultant to Hoffman-LaRoche and Biogen and has participated in educational programs sponsored by Biogen. J.C. is Honorary Visiting Professor in the Department of Cardiovascular Sciences, University of Leicester, UK. C.D. advises Novartis on a safety trial of heart failure treatment and Nova Nordisk on two trials of GLP1 agonist treatment in AD. N.M.P. was a named investigator on the SPRINT-MIND study. B.R.P. is a full-time employee of Life Molecular Imaging Inc. N.C.B.S.S. is a post-doctoral fellow jointly funded by the Michael Smith Health Research BC, the Canadians for Leading Alzheimer Research, and the Canadian Institutes of Health Research. H.M.S. is a full-time employee of the Alzheimer’s Association. J.D.W. was a named investigator on the SPRINT-MIND study. A.H.H. has received honoraria from Eli-Lilly and from NIA, and chairs the Dementias Platform UK Vascular Experimental Medicine group. Funding Information: Research in F.M.E.’s group is supported by National Institute on Aging and Department of Veterans Affairs (IK2CX002180), a Larry L. Hillblom start-up grant (2019A012SUP), and an American Academy of Neurology fellowship. J.M. is appointed at the Netherlands Consortium of Dementia Cohorts (NCDC), which is funded in the context of Deltaplan Dementie from ZonMW Memorabel (project nr 73305095005) and Alzheimer Nederland. C.D. is supported by NIH P30 AG 072972 U19 NS 120384, and UF1NS100608. N.M.P. is supported by R01 AG055606 and R01 AG065805 from the National Institute on Aging. L.S. was supported by a Swiss National Science Foundation award [P2GEP3_191584]. C.E.S. was supported by T32 AG055381 and is presently supported by K01AG071849, both from the National Institute on Aging of the US National Institutes of Health. J.D.W. is supported by R01 AG055606 from the National Institute on Aging. F.J.W. is supported by the Alzheimer's Association (AARF-22-924982) and the Netherlands Organisation for Health Research and Development (ZonMw) (Veni 09150162010108). Research in A.H.H.’s group is funded by the UK Medical Research Council (MR/R005567/1, MR/T033371/1), British Heart Foundation (PG/20/10397), UK Alzheimer's Society, and Alzheimer's Drug Discovery Foundation (20140901). The graphical abstract was prepared using BioRender. The views expressed in this paper are those of the individual authors. Conceptualization, F.M.E. and A.H.H.; ideas, all authors; writing – original draft, A.H.H.; writing – review & editing the final draft, all authors. All authors are members of The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). This perspective arose from a Roundtable discussion on 20/09/2021, hosted by the Vascular Cognitive Disorders Professional Interest Area within ISTAART. F.M.E. serves on the Scientific Advisory Board of Cordance Medical. S.E.B. has been an ad hoc consultant to Hoffman-LaRoche and Biogen and has participated in educational programs sponsored by Biogen. J.C. is Honorary Visiting Professor in the Department of Cardiovascular Sciences, University of Leicester, UK. C.D. advises Novartis on a safety trial of heart failure treatment and Nova Nordisk on two trials of GLP1 agonist treatment in AD. N.M.P. was a named investigator on the SPRINT-MIND study. B.R.P. is a full-time employee of Life Molecular Imaging Inc. N.C.B.S.S. is a post-doctoral fellow jointly funded by the Michael Smith Health Research BC, the Canadians for Leading Alzheimer Research, and the Canadian Institutes of Health Research. H.M.S. is a full-time employee of the Alzheimer's Association. J.D.W. was a named investigator on the SPRINT-MIND study. A.H.H. has received honoraria from Eli-Lilly and from NIA, and chairs the Dementias Platform UK Vascular Experimental Medicine group. One or more of the authors of this paper self-identifies as an under-represented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as living with a disability. Funding Information: Research in F.M.E.’s group is supported by National Institute on Aging and Department of Veterans Affairs ( IK2CX002180 ), a Larry L. Hillblom start-up grant ( 2019A012SUP ), and an American Academy of Neurology fellowship. J.M. is appointed at the Netherlands Consortium of Dementia Cohorts ( NCDC ), which is funded in the context of Deltaplan Dementie from ZonMW Memorabel (project nr 73305095005) and Alzheimer Nederland . C.D. is supported by NIH P30 AG 072972 U19 NS 120384 , and UF1NS100608 . N.M.P. is supported by R01 AG055606 and R01 AG065805 from the National Institute on Aging . L.S. was supported by a Swiss National Science Foundation award [ P2GEP3_191584 ]. C.E.S. was supported by T32 AG055381 and is presently supported by K01AG071849 , both from the National Institute on Aging of the US National Institutes of Health . J.D.W. is supported by R01 AG055606 from the National Institute on Aging . F.J.W. is supported by the Alzheimer's Association ( AARF-22-924982 ) and the Netherlands Organisation for Health Research and Development ( ZonMw ) (Veni 09150162010108 ). Research in A.H.H.’s group is funded by the UK Medical Research Council ( MR/R005567/1 , MR/T033371/1 ), British Heart Foundation ( PG/20/10397 ), UK Alzheimer’s Society , and Alzheimer's Drug Discovery Foundation ( 20140901 ). The graphical abstract was prepared using BioRender. The views expressed in this paper are those of the individual authors. Publisher Copyright: © 2023 The Author(s)

PY - 2023/6/20

Y1 - 2023/6/20

N2 - A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

AB - A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

KW - aging

KW - blood pressure

KW - clinical trials

KW - cognitive impairment

KW - dementia

KW - hypertension

KW - prevention

KW - vascular disease

UR - http://www.scopus.com/inward/record.url?scp=85162213592&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.xcrm.2023.101089

DO - https://doi.org/10.1016/j.xcrm.2023.101089

M3 - Review article

C2 - 37343515

SN - 2666-3791

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 101089

ER -

Elahi FM, Alladi S, Black SE, Claassen JAHR, DeCarli C, Hughes TM et al. Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective. Cell Reports Medicine. 2023 Jun 20;4(6):101089. doi: https://doi.org/10.1016/j.xcrm.2023.101089