Elsevier

NeuroImage

Volume 231, 1 May 2021, 117832
NeuroImage

Vascular risk factors are associated with a decline in resting-state functional connectivity in cognitively unimpaired individuals at risk for Alzheimer's disease: Vascular risk factors and functional connectivity changes

https://doi.org/10.1016/j.neuroimage.2021.117832Get rights and content
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open access

Highlights

  • We present a longitudinal fMRI study in cognitively unimpaired individuals at-risk for AD.

  • Higher cholesterol levels are associated with a reduction in DMN connectivity.

  • Higher diastolic blood pressure is associated with reduced global functional connectivity.

  • Aβ and tau show no association with functional connectivity in a participant subset.

Abstract

Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62 men; mean [SD] age of 63 [5.3] years). Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global (whole-brain) brain functional connectivity and connectivity from canonical functional networks were computed from resting-state functional MRI obtained at baseline and ~3.5 years of annual follow-ups, using a predefined functional parcellation. A subsample underwent Aβ- and tau-PET (n=91). Linear mixed-effects models demonstrated that global functional connectivity increased over time across the entire sample. In contrast, higher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, higher diastolic blood pressure was associated with global functional connectivity reduction. The associations were similar when the analyses were repeated using two other functional brain parcellations. Aβ and tau deposition in the brain were not associated with changes in functional connectivity over time in the subsample. These findings provide evidence that vascular burden is associated with a decrease in functional connectivity over time in older adults with elevated risk for AD. Future studies are needed to determine if the impact of vascular risk factors on functional brain changes precede the impact of AD pathology on functional brain changes.

Keywords

β-Amyloid
Global functional connectivity
Default-mode network
Longitudinal resting-state functional connectivity
tau
Vascular risk factors

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Data used in preparation for this article were obtained from the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease (PREVENT-AD) program (https://douglas.research.mcgill.ca/stop-ad-centre), data release 5.0 (November 30, 2017).