Vascular and haemodynamic issues of brain ageing

Abstract

The population is ageing worldwide, thus increasing the burden of common age-related disorders to the individual, society and economy. Cerebrovascular diseases (stroke, dementia) contribute a significant proportion of this burden and are associated with high morbidity and mortality. Thus, understanding and promoting healthy vascular brain ageing are becoming an increasing priority for healthcare systems. In this review, we consider the effects of normal ageing on two major physiological processes responsible for vascular brain function: Cerebral autoregulation (CA) and neurovascular coupling (NVC). CA is the process by which the brain regulates cerebral blood flow (CBF) and protects against falls and surges in cerebral perfusion pressure, which risk hypoxic brain injury and pressure damage, respectively. In contrast, NVC is the process by which CBF is matched to cerebral metabolic activity, ensuring adequate local oxygenation and nutrient delivery for increased neuronal activity. Healthy ageing is associated with a number of key physiological adaptations in these processes to mitigate age-related functional and structural declines. Through multiple different paradigms assessing CA in healthy younger and older humans, generating conflicting findings, carbon dioxide studies in CA have provided the greatest understanding of intrinsic vascular anatomical factors that may mediate healthy ageing responses. In NVC, studies have found mixed results, with reduced, equivalent and increased activation of vascular responses to cognitive stimulation. In summary, vascular and haemodynamic changes occur in response to ageing and are important in distinguishing “normal” ageing from disease states and may help to develop effective therapeutic strategies to promote healthy brain ageing.

The Influence of Virus Infection on Microglia and Accelerated Brain Aging

“…Physiological aging of the healthy brain is an age-dependent biological process and consists of deterioration of structure and function [ 7 , 8 , 9 , 10 , 11 , 12 ]. However, brain aging can be accelerated by multiple factors, due to traumatic events [ 13 , 14 ], following neurovascular conditions [ 15 , 16 , 17 ], or related to specific brain diseases, including Alzheimer’s and Parkinson’s disease. Accelerated brain aging is often related to enhanced neurodegeneration, which includes loss of neuronal cell structure and function due to (1) metabolic changes [ 18 ], (2) neuronal cell death [ 19 ] (3) decline in the neuronal network [ 20 ], (4) neuronal functional deficiency [ 21 ], (5) decline in neuronal regeneration [ 22 , 23 , 24 ], or (6) a combination of the mentioned reasons.…”

Understanding normal brain aging

“…This issue of Pflügers Archiv-European Journal of Physiology provides a series of review articles and original papers focusing on different key aspects of (patho)physiological brain aging including changes in energy provision [8], the age-dependent accumulation of reactive oxygen/ nitrogen/carbonyl species [8,14], aging of the brain vasculature including the key glial cells involved [2,17] as well as age-related decline in brain wiring [6,13,16,17] and network function [4,6]. Moreover, we focus on the two sensory systems (hearing and olfaction), prone to significant age-related deterioration.…”

“…Moreover, hypersynchrony of neuronal networks also represents a key feature of brain aging [1,6,7,11,15]. This imposes demands of the vascular system, supposed to match an increase in cerebral metabolic activity by an increase in the cerebral blood flow, thus ensuring adequate local oxygenation and nutrient delivery for increased neuronal activity [2].…”

“…Although aging per se is not considered as a disease, it is a major risk factor for cerebrovascular (e.g., stroke) and neurodegenerative (e.g., different kinds of dementia) diseases, which are associated with high morbidity and mortality [2,3,15]. The hearing loss may also lead to social isolation, depression, and decline of cognition [12].…”

“…Interestingly, both pathologies are accompanied by early sleep disturbances and impairment of olfaction [15]. Moreover, age-related alterations of many basic physiological mechanisms, addressed in this volume (e.g., astroglial aging [17], changes in energy metabolism [8] as well as vascular and hemodynamic properties [2]), likely also affect sleep and sleep/wake processes [4].…”