Cerebrovascular influence on brain and cognitive aging

A dysfunctional cerebrovascular system can result in severe adverse effects on brain health and cognitive aging. Recently, Fabiani et al., (2014) introduced a novel non-invasive approach of quantifying cerebrovascular health using diffuse optical imaging in a sample of older adults. This method is based on the estimation of the arterial pulse across the whole scalp. From these estimates, three indices reflecting arterial health can be extracted: pulse amplitude, arterial compliance and pulse transit time. In their initial paper, Fabiani et al. (2014) showed that, in older adults, these indices are correlated with important variables, including volumetric changes in the brain and in psychometric measures. In this thesis, Chapter 1 discusses the importance of cerebrovascular health in brain and cognitive aging followed by a brief introduction to diffusive optical methods and its advantages in quantifying cerebrovascular health. Chapter 2 contains a series of two experiments examining how changes in pulse amplitude reflect changes in cerebrovascular tone (i.e. vasodilation and vasoconstriction) of cerebral blood vessels. We used both a physiological voluntary breath holding task to track generalized changes and a cognitive Sternberg task to track localized changes in cerebrovascular tone. Further, we found that an index of cerebrovascular reactivity derived from the breath holding task was associated with age and cognitive functioning. These results indicate that cerebral pulse amplitude works well as a proxy measure of blood pressure in the brain. Chapter 3 contains a replication and extension of the work presented in Fabiani et al., (2014) to investigate changes in pulse amplitude and arterial compliance in a group of younger and older adults. The study also contains methodological improvements whereby we employed a denser optical recording array and increased data collection time substantially in order improve signal to noise ratio. The results indicate strong reliability for both pulse amplitude and arterial compliance measures. We replicated the initial findings, demonstrating that associations with age, cardiorespiratory fitness, brain anatomy and cognition can also be found across the adult lifespan. Further, we found new evidence supporting the value of regional arterial compliance in predicting working memory performance on the operation word span (OSPAN) task. Chapter 4 contains a study investigating the relationships of arterial compliance with measures of cerebral white matter lesion (manifested as white matter signal abnormalities (WMSA) on T1 weighted images) and white matter microstructure integrity (measured using DTI indices of fractional anisotropy and mean diffusivity). Using hierarchical regression, we found that arterial compliance predicts variance in WMSA over and above age and systemic pulse pressure (difference between systolic blood pressure and diastolic blood pressure), indicating that brain measures of arterial compliance have added predictive utility of WMSA volume over systemic measures of vascular health. Mediation analyses revealed that the relationship between greater age and poorer fluid intelligence (IQ) was mediated sequentially by a reduction in arterial compliance and greater WMSA volume. Additional mediation analyses involving switching the temporal sequence of arterial compliance and WMSA was not statistically significant. Further, substituting WMSA for DTI measures of FA and MD in the mediation analysis also did not reach statistical significance. These results suggest that the cerebrovascular pathway involved in age-related cognitive decline in fluid IQ are mediated primarily through arterial compliance and WMSA, but not changes in white matter microstructure measured by DTI. Tentative findings suggest that vascular damage manifested as poorer arterial compliance and WMSA volume, may converge with degradation to white matter microstructure in the fornix.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Psychology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2016

Author dc:creator

• Tan, Chin Hong

Contributors dc:contributor

• Fabiani, Monica
• Gratton, Gabriele
• Kramer, Arthur F.
• Sutton, Brad
• Dolcos, Florin

• Cerebrovascular health
• aging
• diffuse optical imaging

Statement dc:rights

• Copyright 2016 Chin Hong Tan

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/92950

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/92950