Framingham Risk Score May Also Predict Cognitive Decline

Debra L Beck

May 20, 2020

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

"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," said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

"Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance."

Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.

The researchers followed 1588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest).

Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate β-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the β-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the β-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (β = −0.019), episodic memory (β = −0.023), working memory (β = −0.021), and perceptual speed (β = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (β = –0.012) and visuospatial ability (β = –0.010) did not reach statistical significance.

Bringing Dementia Prevention Into the Exam Room Early

In an interview with | Medscape Cardiology, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

"The link between the cardiovascular risk factors and dementia is well known, but in your doctor's office, that link is not seen. So, if your GP or cardiologist sees you with high blood pressure, he's not immediately going to think about the risk of dementia 20 years later," said Iadecola.

"What this study does is it directly links a simple score that's commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders."

Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. "They think that by making a stroke patient move their hand better, they're treating them, but 30% of stroke patients get dementia 6 or 8 months later and they're missing this link between cerebrovascular pathology and dementia."

Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Hachinski coined the term "brain attack" and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited, given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China . The study was funded by the European Union's Horizon 320230 research and innovation program. Iadecola is a member of the scientific advisory board for Broadview Ventures.

J Am Coll Cardiol. 2020;75:2525-2534. Full text, Editorial


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