PB0738 - Elevated platelet reactivity is associated with blunted neurovascular haemodynamics in healthy middle age and older adults

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Joanne L. Dunster, PhD

Research Fellow
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University Of Reading
Reading, England, United Kingdom

Co-Author(s)

GR

Gabriella MK Rossetti

Research fellow
Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading
Reading, England, United Kingdom
AS

Aamir Sohail

Student
Centre for Human Brain Health, School of Psychology, University of Birmingham
Birmingham, England, United Kingdom
EJ

Elysia Jewett

Student
School of Biological Sciences, University of Reading
Reading, England, United Kingdom
JL

Julie Lovegrove

Professor
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading
Reading, England, United Kingdom
Jonathan M. Gibbins, PhD

Professor
Institute for Cardiovascular and Metabolic Research, School of Biological sciences, University of Reading, Reading, UK
Reading, England, United Kingdom
AC

Anastasia Christakou

Professor
Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading
Reading, England, United Kingdom

Background: Platelet reactivity is elevated in individuals with vascular dementia, but the underlying mechanisms remain largely uncharacterised. At the same time, platelet dysregulation occurs early in cardiovascular pathology, which is also associated with neurodegeneration and dementia.

Aims: To determine whether elevated platelet reactivity is associated with blunted haemodynamic responses to neural activity and, whether the association is explained by systemic vascular reactivity or cerebrovascular reactivity to vasoactive agents.

Methods: Fifty-one healthy middle-aged and older adults (50-80 years) completed this cross-sectional study. Platelet reactivity was assessed by plate-based aggregometry. Haemodynamic responses to neural activity were assessed by BOLD responses in the visual cortex.

Results: Higher platelet reactivity was associated with shorter BOLD HRF full-width half maximum (FWHM) and a longer time to peak in the visual cortex (all R>0.3; P< 0.05). This association was evident across multiple metrics, with the strongest one (surviving correction for multiple comparisons) being the negative correlation between platelet sensitivity (EC50) to the aggregation agonist adenosine 5'-diphosphate (ADP) and BOLD FWHM (R=-0.60; P=0.00005). This association was not explained by systemic vascular reactivity to nitric oxide or cerebrovascular reactivity to carbon dioxide (mediation indirect effects 0.00 to 0.01; P=0.40 to 0.99).

Conclusion(s): Elevated platelet reactivity in healthy older adults was associated with blunted haemodynamic response to neural activation. This association captures a specific link from platelet function to neurovascular coupling, which appears to bypass blunt systemic atherogenic effects. This is the first study to establish a direct mechanistic link between platelet reactivity and neurovascular function in healthy adults.