Association of Cerebral Blood Flow With Longitudinal Changes in Cerebral Microstructural Integrity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

IMPORTANCE Decreased cerebral tissue integrity and cerebral blood flow (CBF) are features of neurodegenerative diseases. Brain tissue maintenance is an energy-demanding process, making it particularly sensitive to hypoperfusion. However, little is known about the association between blood flow and brain microstructural integrity, including in normative aging. OBJECTIVE To assess associations between CBF and changes in cerebral tissue integrity in white matter and gray matter brain regions. DESIGN, SETTING, AND PARTICIPANTSIn this longitudinal cohort study, magnetic resonance imaging was performed on 732 healthy adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective longitudinal study (baseline age of 18-30 years) that examined participants up to 8 times during 30 years (1985-1986 to 2015-2016). Cerebral blood flow was measured at baseline (year 25 of the CARDIA study), and changes in diffusion tensor indices of fractional anisotropy (FA) and mean diffusivity (MD), measures of microstructural tissue integrity, were measured at both baseline and after approximately 5 years of follow-up (year 30). Analyses were conducted from November 5, 2020, to January 29, 2022. MAIN OUTCOMES AND MEASURESAutomated algorithms and linear mixed-effects statistical models were used to evaluate the associations between CBF at baseline and changes in FA or MD. RESULTS After exclusion of participants with missing or low-quality data, 654 at baseline (342 women; mean [SD] age, 50.3 [3.5] years) and 433 at follow-up (230 women; mean [SD] age, 55.1 [3.5] years) were scanned for CBF or FA and MD imaging. In the baseline cohort, 247 participants were Black (37.8%) and 394 were White (60.2%); in the follow-up cohort, 156 were Black (36.0%) and 277 were White (64.0%). Cross-sectionally, FA and MD were associated with CBF in most regions evaluated, with lower CBF values associated with lower FA or higher MD values, including the frontal white matter lobes (for CBF and MD: mean [SE] β = −1.4 [0.

Distance from main arteries influences microstructural and functional brain tissue characteristics

“…Although these parameters provide only a simplistic view on the underlying tissue avoiding more intricate characteristics of WM ( Tournier et al, 2011 ), our findings of a negative correlation of all the relaxation metrics with AD in both cortical GM and WM generally corroborate these reports. Furthermore, more complex models of myelin water fraction pointed to myelin content decline with cerebral blood flow ( Bouhrara et al, 2022 ).…”

Hypertensive Adults Exhibit Lower Myelin Content: A Multicomponent Relaxometry and Diffusion Magnetic Resonance Imaging Study

“…This association is present to a greater extent with white matter tissue damage. 26 , 41 , 57 In fact, myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, and therefore myelin homeostasis is particularly sensitive to hypoperfusion and consequent hypoxia or lack of essential nutrients for myelin synthesis. 58 , 59 Recent in vitro studies have shown that oligodendrocytes are substantially more vulnerable to hypoxia and reduced supply of substrates that provide energy as can occur from hypoperfusion, when compared with other glial cells such as microglia and astroglia.…”

Hypertensive adults exhibit lower myelin content: A multicomponent relaxometry and diffusion MRI study

“…Indeed, recent works have demonstrated that deficits in cerebral blood flow are directly linked to reductions in cerebral tissue integrity. This association is present to a greater extent with white matter tissue damage (25,48,49). In fact, myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, and therefore myelin homeostasis is particularly sensitive to hypoperfusion and consequent hypoxia or lack of essential nutrients for myelin synthesis (50,51).…”

“…Finally, determination of MR parameters can be biased due to several biological and methodological factors. These include, but are not limited to, the effects of magnetization transfer between macromolecules and free water protons, exchange between water pools, J-coupling, off-resonance, spin locking effects, water diffusion within different compartments, flow, temperature, hydration, internal gradients, and architectural features, including fiber fanning or crossing (48). for use under a CC0 license.…”