Brain atrophy, reduced cerebral perfusion, arterial stiffening, and wall thickening with aging coincide with stimulus-specific changes in fMRI-BOLD responses

Abstract

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower grey matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to iso-metabolic and neuro-metabolic stimuli. Additionally, increased carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR) and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age=24±3 y, range=22-28 y; N=13) and old (age=71±4 y; range=67-82 y, N=14) participants, and CBF0, CVR (iso-metabolic %BOLD in response to a breath-hold (BH)), brain activation patterns during a working memory task (neuro-metabolic %BOLD response to N-back trial), GMV, PWV, IMT and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P≤0.050); however, the increase in the %BOLD response to the memory task was not blunted (P≥0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P<0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P≤0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus-specific, brain ageing involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular ageing.