To determine if diastolic dysfunction is a novel modifiable risk factor for the development of cognitive impairment.

The relationship between diastolic dysfunction and cognition is undefined. Our clinical observation is that patients with diastolic dysfunction tend to have impaired executive function and increased white matter hyperintensities on imaging. Diastolic dysfunction is common, disproportionately affects females, and is increasing in the community. If diastolic dysfunction is found to be associated with cognitive impairment, that would suggest diastolic dysfunction is a novel modifiable risk factor for the development of dementia.

Echocardiographic, MRI and neuropsychological data collected by the Framingham Heart Study, Offspring Cohort, at Exam 8 was reviewed. Diastolic measures were related to MRI measures of total cranial brain volume, hippocampal volume and white matter hyperintensities, and to neuropsychological evaluations.

Data from 1438 participants showed that increasing E/E’ ratio, indicating increasing diastolic dysfunction, was associated with increased incident mild cognitive impairment (HR 1.29 [95%CI: 1.01, 1.66], p<0.043). Increasing E/E’ ratio was associated with increased executive function impairment in the Similarities (β±SE:-0.29±0.09,p<0.002) and Phonemic Fluency (-1.28±0.33,p<0.001) tasks. Participants with moderate-to-severe diastolic dysfunction were more impaired on Similarities (-0.62±0.31,p< 0.046) and Phonemic Fluency (-2.60±1.15,p<0.023). Data from 1217 participants showed that those with mild diastolic dysfunction trended towards increased white matter hyperintensities (0.11±0.07, p<0.105); participants with moderate-to-severe diastolic dysfunction had increased white matter hyperintensities (0.30±0.09,p<0.001).

Increasing diastolic dysfunction was associated with worsening executive function on neuropsychological testing, along with increasing cerebral small vessel disease as demonstrated by white matter hyperintensities on MR imaging. As cerebral small vessel disease clinically presents with executive dysfunction, these results align well. This study strongly suggests that diastolic dysfunction is a novel modifiable risk factor for the development of cognitive impairment and dementia. Replication in additional cohorts, and analyses of cognition in treatment trials of diastolic dysfunction would be warranted.