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Aortic Stiffness May Predict Risk for Dementia in Older Adults

Researchers have uncovered a new potential indicator of increased risk for dementia in older adults: stiffness of the aorta. Taking aortic stiffness to be an assessment of cardiovascular health, findings that greater aortic stiffness is associated with increased risk for dementia lends further weight to the growing body of evidence that some forms of dementia—including Alzheimer’s disease—are cardiometabolic problems. The links between cognitive decline and metabolic syndrome are so strong, in fact, that researchers often now refer to “metabolic cognitive syndrome,” rather than just metabolic syndrome.This new phrase hammers home the fact that metabolic syndrome is closely related to cognitive problems.

The study that revealed the association between aortic stiffness and risk for dementia was done at the University of Pittsburgh, and the findings were published in the Journal of Alzheimer’s Disease. Researchers followed 532 non-demented older adults who underwent annual cognitive exams from 1998-99 through 2013. (The study is noteworthy because of this relatively long follow-up period.) During the follow-up period, subjects underwent MRIs and measurements of aortic stiffness, as assessed by carotid-femoral pulse wave velocity (cfPWV). This noninvasive test measures the speed at which the blood pressure pulse travels through the arteries. Aortic stiffness “reduces the buffering of pulsatile blood flow, exposing cerebral small arteries to microvascular damage.”

CfPWV was measured on 356 of the subjects (mean age78; 59% women) between 1996–2000. During the 15-year follow-up period, 212 participants (59.6%) developed dementia, with a median of 4 years between cfPWV test and the dementia diagnosis. After adjusting for age and sex, cfPWV was significantly associated with increased risk for dementia, but mean arterial pressure, pulse pressure, and systolic blood pressure were not. The association also remained after adjusting for education, race, APOE-4 status, diabetes, BMI, and use of antihypertensive medication.

High cfPWV had previously been linked to brain amyloid deposition and to cognitive decline, but until now it was unclear whether aortic stiffness could be an independent predictor of incident dementia. The testing revealed that subjects with high PWV readings were 60 percent more likely to develop dementia during the 16 years of follow-up compared to those with lower PWV measurements.

If aortic stiffness independently predicts increased risk for dementia, the next question must be, what causes aortic stiffness? Identifying risk factors and associations can be helpful in teasing out more details about how various conditions develop, but getting to the root causes—the fundamental drivers—of the conditions would likely provide the most actionable information in terms of treating or potentially even preventing them altogether.

It’s possible that, like any other blood vessel, upon constant exposure to high levels of glucose in the blood, the aorta can become glycated, less pliant, and less accommodating to proper blood flow. Damage to microscopic blood vessels in the eyes and kidneys are a major cause of comorbidities that travel hand-in-hand with type 2 diabetes. Similar damage to the aorta may be contributing to increased stiffness.

In his book, Diabetes Epidemic & You, Joseph Kraft, MD wrote, “Individuals with normal fasting blood glucose may indeed be quite comfortable that they are nondiabetic—that is until they have their first heart attack. […] Those with cardiovascular disease not identified with diabetes are simply undiagnosed.” Many aspects of cardiovascular disease—such as arterial stiffness, dyslipidemia, and hypertension—can be linked strongly to chronic hyperinsulinemia.

It makes sense that aortic stiffness could be a contributing factor in dementia. According to study author Rachel Mackey, Ph.D., M.P.H., an assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, “As the large arteries get stiffer, their ability to cushion the pumping of blood from the heart is diminished, and that transmits increased pulsing force to the brain, which contributes to silent brain damage that increases dementia risk.”

However, in addition to its direct influence on “silent brain damage,” it’s possible that aortic stiffness may serve as a proxy for chronic hyperglycemia and hyperinsulinemia, and that it is those factors that contribute to both the aortic stiffness and the increased risk for dementia. It’s not for nothing that the scientific literature now regularly refers to Alzheimer’s disease as “type 3 diabetes” or an “insulin-resistant brain state.” In fact, according to researchers who study brain fuel metabolism and aging, “Insulin resistance is usually at or near the top of the list of known lifestyle-related factors heightening the risk of declining cognition in the elderly.”

So, if aortic stiffness is a risk factor and a predictor of dementia in older age, the answer isn’t necessarily to reduce aortic stiffness with drugs, although that may be warranted in some situations. The answer is to remove or reduce the dietary, lifestyle, and environmental factors that are likely contributing to both the stiffness and the cognitive decline.

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