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. 2023;91(2):627-635.
doi: 10.3233/JAD-220340.

Metabolic and Vascular Risk Factor Variability Over 25 Years Relates to Midlife Brain Volume and Cognition

Zahra Shirzadi  1   2   3 , Jennifer Rabin  3   4   5   6 , Lenore J Launer  7 , R Nick Bryan  8 , Abdulla Al-Ozairi  9 , Jasmeer Chhatwal  10 , Ebaa Al-Ozairi  9 , John A Detre  11 , Sandra E Black  2   3   5 , Walter Swardfager  3   12   13 , Bradley J MacIntosh  1   2   3
Affiliations

Metabolic and Vascular Risk Factor Variability Over 25 Years Relates to Midlife Brain Volume and Cognition

Zahra Shirzadi et al. J Alzheimers Dis. 2023.

Abstract

Background: Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain imaging features.

Objective: To investigate whether longitudinal changes in MVRF spanning up to 25 years would be associated with midlife brain volume and cognition.

Methods: Participants were from the CARDIA study (N = 467, age at year 25 = 50.6±3.4, female/male = 232/235, black/white = 161/306). Three models were developed, each designed to capture change over time; however, we were primarily interested in the average real variability (ARV) as a means of quantifying MVRF variability across all available assessments.

Results: Multivariate partial least squares that used ARV metrics identified two significant latent variables (partial correlations ranged between 0.1 and 0.26, p < 0.01) that related MVRF ARV and regional brain volumes. Both latent variables reflected associations between brain volume and MVRF ARV in obesity, cholesterol, blood pressure, and glucose. Subsequent bivariate correlations revealed associations among MVRF factors, aggregate brain volume and cognition.

Conclusion: This study demonstrates that MVRF variability over time is associated with midlife brain volume in regions that are relevant to later-life cognitive decline.

Keywords: Brain volume; cognition; metabolic syndrome; partial least squares; vascular risk factors.

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Conflict of interest statement

The authors of this study do not have any conflict of interests to declare.

Figures

Figure 1:
Figure 1:
A visual display of the relationship between the metabolic and vascular risk factors (MVRFs) at year 25 of the CARDIA study (midlife) and visit-to-visit variability (ARV: average real variability) in the corresponding measure. A line of best fit is provided in blue with corresponding confidence intervals. The inset graphs show data at each assessment as a function of time (in study years) for each MVRF.
Figure 2:
Figure 2:
The MVRF ARV partial correlations and ROIs that contribute to (A) the first latent variable, and (B) the second latent variable, obtained from the primary partial least squares analysis. Partial correlation values with error bars that do not cross zero are significant contributors to the latent variables, as denoted by the red colour bars. The significant brain regions for the first and second latent variables are shown in (C) and (D), respectively. A positive correlation denotes an MVRF ARV that was directly related to ROI volumes marked by red colour and inversely related to ROI volumes marked by blue color. For example, the first latent variable showed higher ARV was associated with lower cortical and higher subcortical volumes.
Figure 3:
Figure 3:
Bivariate correlation coefficients among MVRF ARV factors, aggregate brain volume, and cognitive scores. Only significant correlations (P<0.01, with legend provided) are reported, leaving entries blank for non-significant bivariate correlations. By definition, diagonal entries have a value of one.
See this image and copyright information in PMC

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