PT  - JOURNAL ARTICLE
AU  - Kamen A. Tsvetanov
AU  - Richard N.A. Henson
AU  - P. Simon Jones
AU  - Henk-Jan Mutsaerts
AU  - Delia Fuhrmann
AU  - Lorraine K. Tyler
AU  - Cam-CAN
AU  - James B. Rowe
TI  - The effects of age on resting-state BOLD signal variability is explained by cardiovascular and neurovascular factors
AID  - 10.1101/836619
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 836619
4099  - http://biorxiv.org/content/early/2019/11/09/836619.short
4100  - http://biorxiv.org/content/early/2019/11/09/836619.full
AB  - Accurate identification of brain function is necessary to understand neurocognitive ageing, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is therefore essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health and neurovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and neurovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and neurovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and neurovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age-differences in RSFA, after controlling for cardiovascular health. The results were consistent between voxel-level analysis and independent component analysis. Our findings indicate that cardiovascular and neurovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterise neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.