Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease

Alzheimers Dement. 2024 Jul;20(7):4891-4902. doi: 10.1002/alz.14056. Epub 2024 Jun 19.

Abstract

Introduction: Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown.

Methods: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function.

Results: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition.

Discussion: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population.

Highlights: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

Keywords: Alzheimer's disease; biomarker; blood pressure variability; cerebral small vessel disease; neurofilament light.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / epidemiology
  • Atrophy / pathology
  • Biomarkers* / blood
  • Blood Pressure* / physiology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebral Small Vessel Diseases* / blood
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / epidemiology
  • Cognitive Dysfunction / physiopathology
  • Comorbidity
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neurofilament Proteins* / blood
  • White Matter / diagnostic imaging
  • White Matter / pathology

Substances

  • Neurofilament Proteins
  • neurofilament protein L
  • Biomarkers