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Peer-reviewedCC BY-NC-NDActa neuropathologica

Sex differences in the association of late-life blood pressure decline with postmortem brain vessel pathology.

  • Nicholas W Baumgartner1
  • Lianlian Du1
  • Rupal I Mehta1
  • Kaitlin B Casaletto2
  • Madeline Wood Alexander3,4,5
  • Jennifer S Rabin5,6,7
  • Thomas van Sloten8
  • David A Bennett1
  • Ana W Capuano9
  • Zoe Arvanitakis10
10 affiliations
  1. 1Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 W Harrison St, Chicago, IL, 60612, USA.
  2. 2Fein Memory and Aging Center, University of California San Francisco, San Francisco, USA.
  3. 3Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
  4. 4Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
  5. 5Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
  6. 6Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
  7. 7Rehabilitation Sciences Institute, University of Toronto, Toronto, Canada.
  8. 8Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
  9. 9Department of Neurology, University of Chicago, Chicago, USA.
  10. 10Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 W Harrison St, Chicago, IL, 60612, USA. [email protected].
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Abstract

Although hypertension is the leading modifiable risk factor for cerebrovascular disease, less is known about the relation of late-life change in blood pressure (BP) and cerebrovascular pathology beyond brain infarcts. Our previous work found sex-specific associations between declining systolic BP (SBP) and cognitive decline in late-life, suggesting that cerebrovascular pathology may be an upstream contributor to these sex differences. However, postmortem studies have not examined whether BP change differentially relates to vascular brain pathology in men and women, despite well-established sex differences in BP trajectories and cerebrovascular pathology. We examined associations between change in late-life BP and postmortem cerebrovascular (arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy) pathology from 2033 community-dwelling older adults (mean baseline age = 79.7 [SD = 7.1] years; 69% women) from four longitudinal cohort studies with brain autopsy (mean age-at-death = 89.8 [6.6] years). Person-specific late-life BP slopes estimated from annual clinical evaluations over an average of 9.1 [5.7] years were entered in ordinal regressions adjusted for age-at-death, sex, antihypertensive medication use, and BP slope × sex, age-at-death × sex, and BP slope × age-at-death interactions. Faster SBP decline was associated with greater severity of arteriolosclerosis (OR = 1.24, 95%CI 1.08-1.42) and atherosclerosis (OR = 1.41, 95%CI 1.22-1.63). A sex × SBP slope interaction (p = 0.01) revealed a stronger association of SBP decline with arteriolosclerosis severity in women than men. This longitudinal, clinical-pathologic study of older decedents showed sex differences in the association of declining SBP in late-life with severity of arteriolosclerosis, extending prior associations with cognitive decline to cerebrovascular pathology, and suggests potential for longitudinal BP monitoring for precision medicine approaches in cerebrovascular disease risk stratification.

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Cite

BibTeXRIS
BibTeX
@article{baumgartner2026differences,
  title = {{Sex differences in the association of late-life blood pressure decline with postmortem brain vessel pathology.}},
  author = {Nicholas W Baumgartner and Lianlian Du and Rupal I Mehta and Kaitlin B Casaletto and Madeline Wood Alexander and Jennifer S Rabin and Thomas van Sloten and David A Bennett and Ana W Capuano and Zoe Arvanitakis},
  journal = {Acta neuropathologica},
  year = {2026},
  month = oct,
  doi = {10.1007/s00401-026-03107-1},
  url = {https://europepmc.org/article/MED/42925335},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Sex differences in the association of late-life blood pressure decline with postmortem brain vessel pathology.
AU  - Nicholas W Baumgartner
AU  - Lianlian Du
AU  - Rupal I Mehta
AU  - Kaitlin B Casaletto
AU  - Madeline Wood Alexander
AU  - Jennifer S Rabin
AU  - Thomas van Sloten
AU  - David A Bennett
AU  - Ana W Capuano
AU  - Zoe Arvanitakis
PY  - 2026
DA  - 2026/10/24
JO  - Acta neuropathologica
DO  - 10.1007/s00401-026-03107-1
UR  - https://europepmc.org/article/MED/42925335
AB  - Although hypertension is the leading modifiable risk factor for cerebrovascular disease, less is known about the relation of late-life change in blood pressure (BP) and cerebrovascular pathology beyond brain infarcts. Our previous work found sex-specific associations between declining systolic BP (SBP) and cognitive decline in late-life, suggesting that cerebrovascular pathology may be an upstream contributor to these sex differences. However, postmortem studies have not examined whether BP change differentially relates to vascular brain pathology in men and women, despite well-established sex differences in BP trajectories and cerebrovascular pathology. We examined associations between change in late-life BP and postmortem cerebrovascular (arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy) pathology from 2033 community-dwelling older adults (mean baseline age = 79.7 [SD = 7.1] years; 69% women) from four longitudinal cohort studies with brain autopsy (mean age-at-death = 89.8 [6.6] years). Person-specific late-life BP slopes estimated from annual clinical evaluations over an average of 9.1 [5.7] years were entered in ordinal regressions adjusted for age-at-death, sex, antihypertensive medication use, and BP slope × sex, age-at-death × sex, and BP slope × age-at-death interactions. Faster SBP decline was associated with greater severity of arteriolosclerosis (OR = 1.24, 95%CI 1.08-1.42) and atherosclerosis (OR = 1.41, 95%CI 1.22-1.63). A sex × SBP slope interaction (p = 0.01) revealed a stronger association of SBP decline with arteriolosclerosis severity in women than men. This longitudinal, clinical-pathologic study of older decedents showed sex differences in the association of declining SBP in late-life with severity of arteriolosclerosis, extending prior associations with cognitive decline to cerebrovascular pathology, and suggests potential for longitudinal BP monitoring for precision medicine approaches in cerebrovascular disease risk stratification.
SN  - 0001-6322
SN  - 1432-0533
ER  -