Can the Framingham General Cardiovascular Risk Score Accurately Predict Cognitive Decline?

Dementia is a progressive disease in that changes to the brain’s structure and chemistry are irreversible.¹ By 2030, the World Health Organization estimates that 82 million individuals worldwide will be afflicted, up from 50 million in 2017 and a 64% increase in prevalence in just 13 years.²

Adverse cardiovascular health is a well-established risk factor for greater cognitive decline, particularly dementia. However, with there being no effective treatments for the latter,^2,3 an international team of researchers believe that modifying risks detrimental to cardiovascular health may be the answer. Their results were published today in Journal of the American College of Cardiology.

"In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient's cognitive health as they age," stated Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, China, one of the study's authors. "Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance."

Therefore, using the Framingham General Cardiovascular Risk Score (FGCRS), the researchers sought to determine if it had potential as an indicator of cognitive decline in a patient population without a current diagnosis of dementia. This score was based on age, sex, smoking status, systolic blood pressure, and medication use for hypertension, among other criteria. The higher the score, the greater the risk.

Their community-based prospective tudy population comprised 1588 patients from the Rush Memory and Aging Project who were followed for 21 years (average, 6 years) and had a mean (SD) age of 79.5 (7.5) years. Of this group, 378 underwent MRI for brain matter composition, either at study entry or any of the follow-up visits.

FGCRS was measured at study entry (this was the baseline score used for the study), and heart disease risk was divided into 3 categories: low, middle, and high. Nineteen tests were used to measure the following 5 categories of cognitive function each year of the follow-up²:

1. Episodic memory: memory of everyday events
2. Semantic memory: long-term memory
3. Working memory: short-term memory
4. Visuospatial ability: ability to identify visual and spatial relationships among objects
5. Perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns)

The authors discovered that, overall, those in the highest-risk FGCRS category—meaning there were more cardiovascular disease risks—had faster cognitive decline in the areas of episodic memory, working memory, and perceptual speed, speed, compared with the lowest-risk group, as shown by the following²:

• Global cognition: β = —0.019 (95% CI, –0.035 to –0.003)
• Episodic memory: β = —0.023 (95% CI, –0.041 to –0.004)
• Working Memory: β = —0.021 (95% CI, –0.035 to –0.007)
• Perceptual speed: β = —0.027 (95% CI, –0.042 to –0.011)

In addition, among the patients who underwent a brain MRI, higher FGCRS was related to decreases in the size of the brain’s hippocampus region and cortical gray matter, as well as total brain volume, and there was a noticeable increase in white matter hyperintensities (WMH), or lesions, on the brain. Of these findings, “decreased hippocampal and gray matter are typical markers of Alzheimer dementia-related neurodegeneration,” noted the study investigators, while WMH indicate decreased functionality in a certain area. These numbers were reported as follows²:

• Smaller hippocampus volume: β = —0.021 (95% CI, –0.042 to –0.000)
• Less gray matter: β = —1.569 (95% CI, –2.757 to –0.382)
• Total brain volume: β = —1.588 (95% CI, –2.832 to –0.344)
• More white matter hyperintensities: β = —0.035 (95% CI, 0.001-0.069)

“Higher cardiovascular risk burden assessed by FGCRS accelerates cognitive decline in episodic memory, working memory, and perceptual speed. Moreover, higher cardiovascular risk burden is associated with markers of neurodegeneration and vascular lesions in the brain,” the authors concluded. “Our findings highlight the need to monitor and control cardiovascular burden to maintain cognitive health in late life.”

Going forward, an accompanying editorial to the main study suggests the results could assist cardiovascular physicians in educating their patients on cognitive risk factors.³

References

1. How dementia progresses. Alzheimer’s Society. Accessed May 18, 2020. https://www.alzheimers.org.uk/about-dementia/symptoms-and-diagnosis/how-dementia-progresses

2. Song R, Xu H, Dintica CS, et al. Associations between cardiovascular risk, structural brain changes, and cognitive decline. J Am Coll Cardiol. 2020;75(20):2525-2534. doi: 10.1016/j.jacc.2020.03.053

3. Iadecola C, Parikh NS. Framingham General Cardiovascular Risk Score and cognitive impairment: the power of foresight. J Am Coll Cardiol. 2020;75(20):2535-2537. doi: 10.1016/j.jacc.2020.03.061