Diastolic Dysfunction a Common Risk Factor for Cognitive Decline

May 04, 2020

Diastolic dysfunction, a common and often undiagnosed condition in older individuals, could be contributing to the increasing burden of cognitive decline, a new study suggests.

"We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment," lead author Alicia S. Parker, MD, told Medscape Medical News.

Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health, San Antonio.

"This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures," she said.

"Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline," Parker added.

This research is being presented on AAN.com as part of the 2020 American Academy of Neurology Science Highlights.

Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.

"There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address," she added.

"While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health," she commented.

Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. "The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this," she said.

The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.

Results showed that increasing E/E' ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01 – 1.66; P < .043).

An increased E/E' ratio was associated with increased executive function impairment in the "similarities" (β, –0.29; P < .002) and "phonemic fluency" (–1.28; P < .001) tasks.

Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).

Data from 1217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < .001).

The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.

The researchers conclude: "As cerebral small vessel disease clinically presents with executive dysfunction, these results align well." They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.

Earlier Interventions

Commenting on the study for Medscape Medical News, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: "This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline."

Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. "In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting."

Parker responded that this is an area of investigation. "We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility," she said.

Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.

"We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions," Parker replied.

With regard to more specific estimates of the prevalence of diastolic dysfunction, Parker cites another Framingham analysis that involved 2355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.

About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.

Parker has disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2020 Annual Meeting: Abstract S15.005.

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