In a large longitudinal study of older adults (mean age 73 years), we observed an increased probability of death but no increased probability of cognitive impairment among participants with incident CVD compared with an age- and gender-matched control group. This finding contradicts several recent studies indicating that incident CVD accelerates cognitive decline [16–18]. However, there are several key differences between our study and previous studies that may account for our results. Firstly, our study utilized a cumulative incidence analysis accounting for the competing risk of death, which can be thought of as a prognostic model that examines the probability of cognitive impairment occurring in CVD vs. control patients in a real-world setting where death is a possibility [30]. This type of prognostic model that aims to predict likelihood is different than an etiological analysis that aims to infer the causal relationship between CVD and cognitive impairment. One logical interpretation of our results is that higher rates of death may preclude the development of cognitive impairment in a significant portion of the CVD population, as these participants may not live long enough after CVD diagnosis to develop significant cognitive decline. This is consistent with the idea that many of the proposed biologic mechanisms leading to cognitive impairment in CVD patients, such as systemic inflammation, oxidative damage, and subclinical vascular brain injury, are slow-acting processes that take many years to occur [14, 17].
Additionally, in measuring cognitive impairment, our study used a modified version of the TICS (TICS-m), which is a validated cognitive screening tool based on the Mini-Mental State Examination. While the TICS-m has high sensitivity and specificity for cognitive impairment in older adults [24, 25], it is designed to screen for cognitive impairment and does not provide the same degree of granularity as measuring specific domains of cognitive function, such as verbal memory, information processing speed, and temporal orientation, separately. Our results support the notion that CVD patients are not more likely than their non-CVD counterparts to experience global cognitive changes (that would clinically manifest as mild cognitive impairment or dementia) but do not speak to whether CVD patients have declines in cognitive performance in specific domains. Multiple previous studies examining accelerated cognitive decline in CVD patients have examined isolated cognitive domains rather than global cognitive status, and these studies have observed that CVD patients have faster cognitive decline in certain domains, such as verbal memory, information processing speed, and temporal orientation, but not in others, such as executive function and semantic fluency [17, 18]. It is difficult to extrapolate whether these observed declines in specific cognitive domains would translate into global cognitive impairment that manifests clinically.
While the weight of prior evidence has suggested a connection between CVD and cognitive impairment, these findings are not universal. A meta-analysis conducted in 2017 found that taken together, prospective cohort studies showed increased risk of cognitive impairment in individuals with coronary heart disease, defined as individuals with angina pectoris and myocardial infarction, while cross-sectional and case-control studies did not [3]. Another review that analyzed longitudinal studies on cognitive impairment with atrial fibrillation, heart failure, peripheral artery disease, myocardial infarction, and impact of atherosclerotic burden separately found that atrial fibrillation and severe atherosclerosis were risk factors for cognitive decline but that the body of literature on heart failure, peripheral artery disease, and myocardial infarction was too small to draw any conclusions [8]. There is also significant heterogeneity across the literature in how CVD and cognitive impairment are defined and measured. Since CVD is a general term that can be comprised of many cardiovascular-related conditions (e.g. myocardial infarction, coronary artery disease, heart failure, arrythmia, stroke, etc.), studies have included different conditions in their analyses. Cognitive impairment is also a very broad term that can be defined and segmented in different ways (e.g. mild cognitive impairment vs. dementia, non-amnesiac cognitive impairment vs. amnesiac cognitive impairment), or examined by looking at domains of cognition (e.g. verbal memory, information processing speed, temporal orientation). This methodological heterogeneity makes it difficult to draw broader conclusions from the current body of literature. Further, it is also important to consider that bias towards publishing positive results may have played a role in shaping the current literature landscape.
Our study has several strengths, including a well-characterized dataset with a large sample size and serial cognitive assessments over nearly a decade of follow-up. Our study also has several important limitations. First, we relied on self-reported CVD. While we used an established HRS methodology to apply rigor to this process, we also found that participants with inconsistencies in self-report were more likely to have cognitive impairment, suggesting that cognitive status did play a role in participants’ abilities to report on their cardiovascular disease status. However, our sensitivity analysis that included participants with self-report discrepancies still showed no difference in incidence of cognitive impairment between CVD and control groups. Utilizing self-report also resulted in a broader analysis of cognitive impairment in CVD overall, as opposed to a more focused analysis looking at cognitive impairment in one type of CVD, such as heart failure or myocardial infarction. While this limited the specificity of our analysis, prior research has proposed an association between cognitive impairment and the range of cardiac conditions, such as heart failure, myocardial infarction, atrial fibrillation, and coronary artery disease, that were included in our definition of CVD [4, 6, 7, 16, 18].
A second limitation is that several variables were not available in in our dataset and may have influenced the results. For example, we lacked robust data on the severity of participants’ CVD or how they managed their symptoms. It is possible that patients with more severe atherosclerotic disease burden were more likely to develop cognitive impairment. Third, our sample included primarily non-Hispanic white participants, which does not reflect the diversity of race and ethnicity present in the U.S. population and limits the generalizability of our results. Fourth, we excluded a significant portion of the HRS population with CVD due to missing covariate data and age restrictions that were used to generate a sufficient matched cohort. Fifth, we did not control for presence of the ApoE4 allele, which some past studies on CVD and cognition accounted for given its strong association with dementia [34]. Lastly, we did not have data on specific cognitive domains, so we were unable to analyze cognitive impairment at a more granular level as other studies have done.