Dataset Information

The Metabolic Syndrome Is Associated With Lower Cognitive Performance and Reduced White Matter Integrity in Midlife: The CARDIA Study.

ABSTRACT:

Background

Cardiovascular disease risk factors play a critical role in brain aging. The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, has been associated with poorer cognition in old age; however, it is unclear if it is connected to brain health earlier in life.

Methods

We investigated the association of MetS (n = 534, 18.5%) vs. no MetS (n = 2,346, 81.5%) with cognition in midlife within the prospective study, Coronary Artery Risk Development in Young Adults (CARDIA). At midlife (mean age 50), MetS was defined using National Cholesterol Education Program guidelines. At the 5-year follow-up, a cognitive battery was administered including tests of processing speed (Digit Symbol Substitution Test, DSST), executive function (the Stroop Test), verbal memory (Rey Auditory Verbal Learning Test, RAVLT), verbal fluency (category and letter fluency), and global cognitive function (Montreal Cognitive Assessment, MoCA). A sub-sample (n = 453) underwent brain MRI.

Results

Participants with MetS had worse performance on tests of verbal fluency, processing speed, executive function, and verbal memory (p < 0.05), but not on global cognition. MetS was also associated with lower frontal, parietal, temporal, and total white matter integrity (p < 0.05), as assessed with fractional anisotropy.

Conclusions

MetS is associated with lower cognition and microstructural brain alterations already at midlife, suggesting that MetS should be targeted earlier in life in order to prevent adverse brain and cognitive outcomes.

SUBMITTER: Dintica CS

PROVIDER: S-EPMC9339689 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

The Metabolic Syndrome Is Associated With Lower Cognitive Performance and Reduced White Matter Integrity in Midlife: The CARDIA Study.

Dintica Christina S CS Hoang Tina T Allen Norrina N Sidney Stephen S Yaffe Kristine K

Frontiers in neuroscience 20220718

<h4>Background</h4>Cardiovascular disease risk factors play a critical role in brain aging. The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, has been associated with poorer cognition in old age; however, it is unclear if it is connected to brain health earlier in life.<h4>Methods</h4>We investigated the association of MetS (<i>n</i> = 534, 18.5%) vs. no MetS (<i>n</i> = 2,346, 81.5%) with cognition in midlife within the prospective study, Coronary Artery Risk Develo ...[more]

PMID: 35924230

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Project description:ObjectiveElevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife.MethodsParticipants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models.ResultsLower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (β = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; β = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (β = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (β = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors.ConclusionIncreasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Project description:Despite increasing knowledge about the effects of phenylketonuria on brain structure and function, it is uncertain whether white matter microstructure is affected and if it is linked to patients' metabolic control or cognitive performance. Thus, we quantitatively assessed white matter characteristics in adults with phenylketonuria and assessed their relationship to concurrent brain and blood phenylalanine levels, historical metabolic control and cognitive performance. Diffusion tensor imaging and 1H spectroscopy were performed in 30 adults with early-treated classical phenylketonuria (median age 35.5 years) and 54 healthy controls (median age 29.3 years). Fractional anisotropy and mean, axial and radial diffusivity were investigated using tract-based spatial statistics, and white matter lesion load was evaluated. Brain phenylalanine levels were measured with 1H spectroscopy whereas concurrent plasma phenylalanine levels were assessed after an overnight fast. Retrospective phenylalanine levels were collected to estimate historical metabolic control, and a neuropsychological evaluation assessed the performance in executive functions, attention and processing speed. Widespread reductions in mean diffusivity, axial diffusivity and fractional anisotropy occurred in patients compared to controls. Mean diffusivity and axial diffusivity were decreased in several white matter tracts and were most restricted in the optic radiation (effect size rrb = 0.66 to 0.78, P < 0.001) and posterior corona radiata (rrb = 0.83 to 0.90, P < 0.001). Lower fractional anisotropy was found in the optic radiation and posterior corona radiata (rrb = 0.43 to 0.49, P < 0.001). White matter microstructure in patients was significantly associated with cognition. Specifically, inhibition was related to axial diffusivity in the external capsule (rs = -0.69, P < 0.001) and the superior (rs = -0.58, P < 0.001) and inferior longitudinal fasciculi (rs = -0.60, P < 0.001). Cognitive flexibility was associated with mean diffusivity of the posterior limb of the internal capsule (rs = -0.62, P < 0.001), and divided attention correlated with fractional anisotropy of the external capsule (rs = -0.61, P < 0.001). Neither concurrent nor historical metabolic control was significantly associated with white matter microstructure. White matter lesions were present in 29 out of 30 patients (96.7%), most often in the parietal and occipital lobes. However, total white matter lesion load scores were unrelated to patients' cognitive performance and metabolic control. In conclusion, our findings demonstrate that white matter alterations in early-treated phenylketonuria persist into adulthood, are most prominent in the posterior white matter and are likely to be driven by axonal damage. Furthermore, diffusion tensor imaging metrics in adults with phenylketonuria were related to performance in attention and executive functions.

Project description:IntroductionReduced white matter integrity outside the stroke lesion may be a potential contributor of post-stroke cognitive impairment. We aimed to investigate how a stroke lesion affects the integrity of surrounding white matter, and whether the integrity of the non-lesioned part of white matter tracts is associated with cognitive performance after ischemic stroke in young adults.MethodsPatients from the ODYSSEY study, aged 18-49 years, with a first-ever ischemic stroke, underwent 3T MRI and cognitive assessment within six months after the index event. Using TractSeg and free water imaging, we analyzed free water corrected fractional anisotropy (FAT), free water corrected mean diffusivity (MDT), and free water (FW) of all white matter tracts outside the stroke lesion. We calculated FAT and FW in the lesioned white matter tracts at 2 mm incremental distances from the lesion, extending up to 10 mm, represented as Z-scores using the diffusion measures of controls. We categorized patients as no/mild or major vascular cognitive disorder (VCD) and compared with a stroke-free control group (n = 23). Group differences in diffusion measures were examined. We investigated associations between FAT, FW and cognitive performance across seven domains.ResultsAmong 66 patients (median age 40.3 years (IQR 31.3-46.2); 54.5 % women), 22 had major VCD. In the different lesion expansions, we found differences in FAT (p = 0.009) and FW (p = 0.049). Patients with major VCD had lower FAT [range of Cohen's d (0.65; 1.65)] and higher FW [Cohen's d (-1.40; -0.64)] values compared to controls, both in the hemisphere affected by the lesion and the unaffected hemisphere. Performance in processing speed correlated with FAT across eight tracts in the affected hemisphere [range of R2adj (0.30; 0.37)], and with FW in four tracts in the affected and three in the unaffected hemisphere [R2adj (0.28; 0.38)].DiscussionIn the first months after a stroke, we observed a trend of microstructural changes remote from the lesion that diminish as the distance from the lesion increases. Tissue changes in the white matter outside the lesion are present in both hemispheres, but are more pronounced in the hemisphere affected by the stroke, and may contribute to worse cognitive performance.

Dataset Information

The Metabolic Syndrome Is Associated With Lower Cognitive Performance and Reduced White Matter Integrity in Midlife: The CARDIA Study.

Background

Methods

Results

Conclusions

Publications

The Metabolic Syndrome Is Associated With Lower Cognitive Performance and Reduced White Matter Integrity in Midlife: The CARDIA Study.

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