Vascular risk factors are associated with longitudinal changes in cerebrospinal fluid tau markers and cognition in preclinical Alzheimer's disease

Alzheimers Dement. 2019 Sep;15(9):1149-1159. doi: 10.1016/j.jalz.2019.04.015. Epub 2019 Aug 1.


Introduction: Vascular factors increase the risk of Alzheimer's disease (AD). We investigated the associations between such factors, longitudinal AD cerebrospinal fluid biomarkers, and cognition.

Methods: 433 cognitively normal participants were classified into four biomarker groups using their baseline amyloid (A+/-) and tau status (T+/-). 184 participants had undergone serial cerebrospinal fluid collection. Frequencies of risk factors and the Framingham Risk Score (FRS) were compared, and we tested the influence of risk factors on change in biomarker concentrations and cognition.

Results: The absence of obesity, presence of hypertension, and a high FRS were associated with an increase in tau levels, particularly in A+T+ individuals. Risk factors were not associated with amyloid. Depression was associated with higher cognitive scores, whereas high FRS was associated with lower scores and a faster decline.

Discussion: Our results demonstrate that vascular risk factors may enhance neurodegeneration but not amyloid accumulation in preclinical AD.

Keywords: Alzheimer's disease; Amyloid-β; Biomarkers; Cardiovascular disorders; Cerebrospinal fluid; Dementia; Depression; Framingham Risk Score; Hypercholesterolemia; Hypertension; Neurodegeneration; Obesity; Tau; Vascular risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Cardiovascular Diseases / prevention & control
  • Cognition*
  • Female
  • Humans
  • Hypertension / blood
  • Male
  • Prodromal Symptoms*
  • Risk Factors
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins