{"doi":"10.1113/jp279949","title":"Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?","abstract":"Cognitive decline naturally occurs with healthy ageing. However, accelerated decline can have grave implications, as increased cognitive decline is associated with increased risk of developing Alzheimer's disease-related dementias (ADRDs). Currently, ADRDs are a key research priority for the National Institute on Aging. As the USA's population continues to grow older, the prevalence of cognitive decline is likely to rise. Studies support a direct correlation between cerebrovascular function and cognition (Thorin-Trescases et al. 2018). This is plausibly due to age-related changes in large elastic artery stiffness and vascular endothelial function. In young adults, large peripheral elastic arteries (e.g. the aorta and carotids) serve to dampen large swings in arterial blood pressure produced with each heartbeat. This, in turn, slows the velocity of blood as it flows towards the resistance arteries of the brain. The endothelium and vascular smooth muscle cells within these resistance vessels then sense this change in pulse pressure, dilating in response (Thorin-Trescases et al. 2018). However, these mechanisms become impaired with advancing age. A common hallmark of vascular ageing is increased large elastic artery stiffness. Vascular hypertrophy derived from lifelong distension and recoil of the vessels induces arterial remodelling, whereby elastin fibres within the vascular walls become fragmented and are replaced with stiffer collagen fibres, decreasing the ability of the arteries to absorb changes in pulse pressure (Thorin-Trescases et al. 2018). Subsequently, pulse pressure increases and impairs vascular endothelial function, altering the ability of the endothelium to respond to vasodilatory stimuli, such as CO2. Along with being an independent risk factor for cardiovascular disease, increased arterial stiffness is associated with increased risk of cognitive decline. One measure of cerebrovascular function which is sensitive to changes in arterial compliance is cerebrovascular reactivity (CR), or the ratio of cerebral artery blood flow response to a CO2 stimulus. Importantly, CR decreases with advancing age and is directly associated with cognitive decline (Thorin-Trescases et al. 2018). Therefore, CR may not just be a measure of cerebrovascular function; it may provide insight into current and future cognitive health. Spaceflight is believed to be an accelerated model of vascular ageing. Indeed, data from different studies support age-related morphological and functional changes to astronaut vasculature over the course of long duration (6 months) spaceflight missions. For one 6-month mission on the International Space Station (ISS), echography was used to measure the intima–media thickness (IMT) in the carotid and femoral arteries of astronauts preflight, inflight and postflight (Arbeille et al. 2016). Increased IMT is considered a risk factor for cardiovascular diseases (e.g. atherosclerosis), and IMT increases progressively with age (Arbeille et al. 2016). For these astronauts, the average increase in IMT was 12%. This increase in IMT is indicative of accelerated ageing, as a 12% increase in IMT is equivalent to 20–30 years of vascular ageing (Arbeille et al. 2016). Although this increase in IMT is alarming, it is unclear whether these changes to IMT will persist long-term, as Arbeille et al. (2016) only noted elevated IMT 4 days postflight. In another study, Hughson et al. (2016) investigated how spaceflight alters carotid artery stiffness via carotid artery distensibility coefficient and -stiffness index (two indicators of arterial stiffness). After 6 months of spaceflight aboard the ISS, all astronauts had a decreased carotid artery distensibility coefficient (20% change, preflight to postflight) and increased -stiffness index (25% change, preflight to postflight), indicating increased arterial stiffness (Hughson et al. 2016). Importantly, this study demonstrated that even with unaffected blood pressure regulation, sp","journal":"The Journal of Physiology","year":2020,"id":115651,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542266,"name":"Alyssa N. Cavalier","orcid":"0000-0002-4402-6208","position":1,"is_corresponding":false},{"id":307104,"name":"Zachary S. Clayton","orcid":"0000-0003-3878-3533","position":2,"is_corresponding":false},{"id":307106,"name":"David A. Hutton","orcid":"0000-0002-5827-6953","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-18T23:13:40.596604Z","pmid":"32468584","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}