1. Decreases in total brain volume and within specific regions such as the hippocampus were associated with vascular risk factors such as alcohol consumption and smoking, while protective factors such as favorable cholesterol profiles were associated with increased brain volumes.
2. Brain volume changes within the hippocampus, posterior cingulate gyrus and precuneus were proportionately associated with risk for early cognitive changes predictive of dementia.
Evidence Rating Level: 2 (Good)
Study Rundown: Evidence is growing that vascular risk factors predispose to the development of Alzheimer disease (AD). While some risk factors are non-modifiable, such as genetics, many vascular risk factors are present long before the development of cognitive deficits and can be managed and potentially delay or prevent progression to AD. Prior neuroimaging studies have shown an association between decreased brain volume in regions associated with executive function and cognitive decline. The current study sought to determine which vascular risk factors can be directly and independently associated with both brain volume losses and cognitive decline. Using a large, multiethnic cohort based in Texas, study participants who underwent baseline brain magnetic resonance imaging (MRI) were reimaged at a 7-year interval evaluating for volume changes in the hippocampus, posterior cingulate gyrus and precuneus as these regions are associated with memory retrieval and consolidation. Additionally, subject’s cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) to identify mild cognitive impairment and preclinical AD. The results confirmed that lower cognitive test scores correlated with lower brain volumes in each area, and that the volume of specific brain regions was associated with the presence or absence of specific vascular risk factors. Specifically, alcohol consumption and smoking were associated with decreased hippocampal volume, while additional factors such as obesity and diabetes were associated with lower total brain, precuneus and posterior cingulate volumes. These volumetric decreases were directly correlated to decreased MoCA scores, transitively associating vascular risk factors with pre-dementia cognitive decline through brain volume loss. Among patients over age 50, the hippocampus and precuneus volumes were most strongly associated with later cognitive decline, while in those under age 50, the posterior cingulate volume was a stronger predictor. This study utilized a cross-sectional design, thereby limiting the generalizability of their findings in a longitudinal cohort. Additional longitudinal studies employing more robust technology can provide information to help predict the impact of specific cardiovascular risk factors on the development and progression of AD.
In-Depth [prospective cohort]: A total of 1629 eligible subjects (mean age: 50.0 years ± 10.2) from the Dallas Heart Study participants were included for this study, all of whom received baseline and repeated MRI studies with autovolumetry with attention to specific brain structures significant for cognition. The subjects were split into 2 age groups surrounding the mean 50 years of age (805 < 50 years; 824 ≥ 50 years) and then underwent screening with the MoCA. The MoCA is a cognitive test focused on various functional domains including attention, concentration, executive functions, memory, language, and orientation. In patients younger than 50, MoCA scores were associated with posterior cingulate volume (p = .001), while in patients 50 years and above the MoCA score was associated instead with regional volume changes in the hippocampus (p < .05) and precuneus (p < .023). The assessments were repeated again 7 years after the initial baseline studies and outcomes from both timepoints were interpreted with regressional analysis to evaluate association between cardiovascular risk factors and cognitive function along with brain volume changes in the hippocampus, precuneus, and posterior cingulate cortex. Total blood cholesterol levels (p = .050) coincided with larger posterior cingulate volume. Similar associations were found for cholesterol components; including high-density lipoprotein (p = .003) and low-density lipoprotein (p = .037). Larger precuneus volumes were measured in subjects with higher triglyceride levels (p = .004). Smaller hippocampal volume was associated with consumption of toxins such as alcohol (p = .039) and nicotine use in smoking (p = .048).
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