Subclinical Atherosclerosis, Dementia Entwined in People in Their 80s and Beyond

People who reach age 80 without signs of cardiovascular problems or mental deterioration are more likely to develop dementia than suffer from heart disease as they get older, a new study shows. Moreover, subclinical atherosclerosis indicated by coronary artery calcification (CAC) is associated with a higher risk of mortality overall and of dementia and coronary heart disease in certain subsets.

“Unfortunately, very few older individuals have low CAC scores because of a lifetime history of high cardiovascular risk factors,” lead author Lewis Kuller, MD, DrPH (University of Pittsburgh), told TCTMD in an email.

There could be “very substantial clinical implications” if the results, published in the March 8, 2016, issue of the Journal of the American College of Cardiology, are confirmed in other studies, he said.

“Aggressive prevention and treatment of cardiovascular disease risk factors beginning at younger or middle ages to prevent development and progression of CAC or atherosclerosis and arteriosclerosis could not only increase longevity and reduce risk of coronary heart disease but also be a very effective approach for prevention of dementia and, therefore, increase active life expectancy,” he said.

Thus, he said, “there is an urgent need for both further validation of these observations in the elderly and likely clinical trials to determine whether prevention of atherosclerosis and arteriosclerosis will reduce burden of brain pathology and risk of dementia.”

Because of improvements in prevention and treatment of cardiovascular disease, the average lifespan has increased, expanding the size of the older population at risk for dementia. Although prior studies have found a link between vascular disease and dementia, it has remained unclear whether people who survive to age 80 without substantial atherosclerosis have lower risks of dementia and brain neuropathology, according to the authors.

To explore the issue, the investigators examined data on 532 participants in the Cardiovascular Health Study-Cognition Study who were free from dementia and cardiovascular disease at baseline in 1998-1999 (mean age 80 years) and had various measures of subclinical atherosclerosis available. They were followed until 2012-2013 (mean age 93 years) and underwent yearly neuropsychological testing.

Overall, 36% of participants had CAC scores over 400. Women and black patients tended to have lower scores compared with men and white patients. Few men had low CAC scores.

CAC Extent Predicts Poorer Outcomes

One-quarter of the deaths during follow-up were caused by coronary heart disease, 6% by stroke, and 16% by dementia. Nearly two-thirds (64%) of the participants who died, however, had been diagnosed with dementia.

Having a CAC score over 400 vs less than 10 independently predicted total mortality in the overall cohort (HR 1.73; 95% CI 1.18-2.54). But when broken down by sex and race, increasing CAC scores were related to mortality in white men and black women only.

As for dementia, incidence increased along with CAC score in white women only (P =.044), although the authors note that the analysis was limited by the low number of participants.

The age-specific incidence of dementia was higher than that of coronary heart disease at all ages in women and older ages in men, who were more likely to develop coronary disease than were women.

Overall, having a CAC score over 400 was only nonsignificantly related to risk of incident coronary disease (HR 1.54; 95% CI 0.83-2.86). Increasing CAC scores, however, were tied to elevated coronary heart disease risks in white men and both white and black women.

Can Preventing Atherosclerosis Lessen Dementia Burden?

The results of the study suggest that “the prevalence of dementia in older populations will likely increase with continued improvement in prevention and treatment of [coronary heart disease] and increasing longevity of the population, assuming that no new therapies either prevent or delay the onset of incident dementia,” the authors say. “As age at first heart attack continues to rise, dementia will be an important comorbidity and will affect treatment decisions and outcomes.”

It remains to be seen whether preventing atherosclerosis will lower rates of dementia, they add.

“If delay or prevention of peripheral atherosclerosis resulted in the reduction or slowing of progression of brain neuropathology and subsequent incidence of dementia, then there is the potential for a very substantial impact on reducing most dementia in very old ages (eg, 80-plus years of age),” they write.

“The alternative,” they say, “could be an unfortunate outcome: that successful control of risk factors and treatment of [coronary disease] results in an increasing epidemic of dementia among older people.”

In fact, the results of the study “reinforce the notion that as more individuals live to older ages, we can expect a dramatic increase in the incidence and prevalence of dementia,” argue Walter Swardfager, PhD (Sunnybrook Research Institute; Toronto, Canada), and Sandra Black, MD (Sunnybrook Health Sciences Center; Toronto), in an accompanying editorial.

“Atherosclerosis, even if clinically undeclared, will likely contribute to these cases, suggesting the importance of pharmacological and nonpharmacological management of vascular risk factors beginning in midlife,” they continue. “Accurate, well-understood predictive biomarkers and precisely targeted intervention studies are urgently needed to optimize cognitive and functional outcomes that support the healthy longevity of the body and mind.”

Sources: 
Kuller LH, Lopez OL, Mackey RH, et al. Subclinical cardiovascular disease and death, dementia, and coronary heart disease in patients 80+ years. J Am Coll Cardiol. 2016;67:1013-1022.
Swardfager W, Black SE. Coronary artery calcification: a canary in the cognitive coalmine. J Am Coll Cardiol. 2016;67:1023-1026.

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