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Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance.

ABSTRACT: Midlife metabolic and vascular risk factors (MVRFs) predict cognitive decline and dementia; however, these risk factors tend to overlap, and the mechanisms underlying their effects on cognitive performance are not well understood. This cross-sectional study investigates the contributions of MVRFs to regional cerebral blood flow (CBF) and verbal learning & memory among middle-aged adults. We used partial least squares (PLS) analysis to create latent risk factor profiles and examine their associations to CBF in 93 regions of interest among 451 participants (age 50.3?±?3.5?years) of the Coronary Artery Risk Development in Young Adults. This multivariate analysis revealed regional CBF was lower in relation to obesity (higher body mass index and waist circumference), dysregulated glucose homeostasis (higher fasting glucose, oral glucose tolerance, and higher fasting insulin), and adverse fasting lipid profile (lower high-density lipoprotein cholesterol and higher triglycerides). In a sensitivity analysis, we found that significant associations between MVRFs and CBF were prominent in the hypertension-medicated subgroup. In a mediation model, the PLS-based MVRFs profile was associated with memory performance (rey auditory verbal learning test); however, CBF was not a significant mediator of this association. The results describe an adverse midlife metabolic profile that might set the stage for incipient dementia and contribute to widespread changes in CBF.

SUBMITTER: MacIntosh BJ

PROVIDER: S-EPMC7267901 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance.

MacIntosh Bradley J BJ Shirzadi Zahra Z Atwi Sarah S Detre John A JA Dolui Sudipto S Bryan Robert Nick RN Launer Lenore J LJ Swardfager Walter W

Human brain mapping 20191025 4

Midlife metabolic and vascular risk factors (MVRFs) predict cognitive decline and dementia; however, these risk factors tend to overlap, and the mechanisms underlying their effects on cognitive performance are not well understood. This cross-sectional study investigates the contributions of MVRFs to regional cerebral blood flow (CBF) and verbal learning & memory among middle-aged adults. We used partial least squares (PLS) analysis to create latent risk factor profiles and examine their associat ...[more]

PMID: 31651075

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Project description:BackgroundCerebral blood flow (CBF) is critically important in the overall maintenance of brain health, and disruptions in normal flow have been linked to the degradation of the brain's structural integrity and function. Recent studies have highlighted the potential role of CBF as a link between psychiatric disorders and brain integrity. Although interpersonal early life trauma (IP-ELT) is a risk factor for the development of psychiatric disorders and has been linked to disruptions in brain structure and function, the mechanisms through which IP-ELT alters brain integrity and development remain unclear. The goal of this study was to understand whether IP-ELT was associated with alterations in CBF assessed during adulthood. Further, because the cognitive implications of perfusion disruptions in IP-ELT are also unclear, this study sought to investigate the relationship between IP-ELT, perfusion, and cognition.Methods179 Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) Veterans and military personnel completed pseudo-continuous arterial spin labeling (pCASL) imaging, clinical interviews, the Traumatic Life Events Questionnaire (TLEQ), and a battery of neuropsychological tests that were used to derive attention, memory, and executive function cognitive composite scores. To determine whether individuals were exposed to an IP-ELT, events on the TLEQ that specifically queried interpersonal trauma before the age of 18 were tallied for each individual. Analyses compared individuals who reported an interpersonal IP-ELT (IP-ELT+, n = 48) with those who did not (IP-ELT-, n = 131).ResultsWhole brain analyses revealed that IP-ELT+ individuals had significantly greater CBF in the right inferior/middle temporal gyrus compared to those in the IP-ELT- group, even after controlling for age, sex, and posttraumatic stress disorder (PTSD). Further, perfusion in the right inferior/middle temporal gyrus significantly mediated the relationship between IP-ELT and memory, not attention or executive function, such that those with an IP-ELT had greater perfusion, which, in turn, was associated with poorer memory. Examination of other clinical variables such as current PTSD diagnosis and severity as well as the interaction between IP-ELT and PTSD yielded no significant effects.ConclusionsThese results extend prior work demonstrating an association between ELT and cerebral perfusion by suggesting that increased CBF may be an important neural marker with cognitive implications in populations at risk for psychiatric disorders.

Dataset Information

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance.

Publications

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance.

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