Author + information
- aResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, and the Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, FinlandResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, and the Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
- bPaavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, FinlandPaavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland
- cDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, FinlandDepartment of Clinical Physiology and Nuclear Medicine, University of Turku, Turku, Finland
- ↵∗Address for correspondence:
Dr. Suvi P. Rovio, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Cardiovascular diseases remain the leading causes for mortality and disability (1). Simultaneously, impaired cognitive function has become 1 of the greatest global challenges for public health (2). Cardiovascular diseases and cognitive decline share many risk factors, such as elevated serum low-density lipoprotein cholesterol, high blood pressure, obesity, hyperglycemia and diabetes mellitus, physical inactivity, smoking, and poor diet—all of which have been linked to both disorders in midlife and old age (1,2). Additionally, recent research has widened the time window in which these risk factors start to exert their influence on cardiovascular health (3) and cognitive function (4,5). Shared life-course risk factors identified in longitudinal studies have indicated convoluted links between cardiovascular and brain health. These links suggest that compromised cardiovascular risk factor levels from early age may damage both vascular and neuronal tissues of the brain. The exact mechanisms underlying these associations, however, have still remained unclear. The risk factors are known to provoke atherosclerosis, which eventually leads to restrained function of the blood-brain barrier, cerebral hypoperfusion, as well as small- or even large-vessel disease, including microinfarcts, in the brain. Additionally, cardiovascular risk factors may induce oxidative stress, endothelial dysfunction, and adverse immune responses, which may contribute to neurodegenerative processes with the potential to affect cognitive function, including cerebral accumulation and clearance of amyloid-beta-peptide (i.e., the hallmark of the major cause for dementia, Alzheimer’s disease). Thus, previous research has mainly considered pathophysiological cerebrovascular alterations as the main mechanistic pathway between cardiovascular health and cognitive function.
As the previous studies have elucidated the life-course perspective to cognitive function, it is important to define factors that could act as triggers altering the slope of the cognitive trajectories. The study by Xie et al. (6) in this issue of the Journal contributes to this question by leveraging the longitudinal community-based data from the ELSA (English Longitudinal Study of Aging). The study provides evidence on the role of incident coronary heart disease as a possible factor bending the course of cognitive decline trajectory in older age. The investigators compared the slope of trajectories among persons with incident coronary heart disease during the follow-up to those who remained without the disease in 3 cognitive domains—verbal memory, semantic fluency, and temporal orientation—as well as in general cognitive function composed from the separate cognitive domains. They studied the associations of the time window before the incident coronary heart disease as well as short- and long-term associations after the event among 7,888 stroke-free participants of the ELSA.
The results from the present study indicated a steeper long-term post-event decline in general cognitive function for the participants with an incident coronary heart disease, and the findings showed most robust associations for verbal memory. Specifically for verbal memory, the associations might reflect the specific vulnerability for altered vascular function in the brain structures related to this cognitive domain (i.e., medial temporal lobe and hippocampus). Furthermore, the study by Xie et al. (6) found no short-term associations between incident coronary heart disease and acceleration of cognitive decline. This finding is interesting given that previous research has often supported the hypothesis that the link between cardiovascular health and cognitive function is via cerebrovascular-related structural brain damage, which manifests as acute cognitive impairment and/or accelerated short-term cognitive decline. The finding from the present study provides evidence that the coronary heart disease event as such does not necessarily cause acute structural alterations in the brain (e.g., microinfarcts), but that the incident coronary heart disease might act more via longer-term alterations affecting the cerebral vascular function (e.g., the function of the blood-brain barrier as well as perfusion and oxidation in the brain).
The authors found no difference in the slope of cognitive decline prior to the coronary heart disease event among those who did or did not develop incident coronary heart disease. This finding is interesting for 2 reasons: first, because the clinical cognitive impairment is suggested to be preceded by subclinical deficiencies (e.g., in memory skills, learning, and decision making) already years or even decades before they become clinically detectable; and second, because the persons who developed incident coronary heart disease in the present study had higher levels of cardiovascular risk factors (e.g., higher systolic and diastolic blood pressure, body mass index, as well as more often diabetes, and unhealthier lifestyle) throughout the follow-up, which could be hypothesized to have caused subtle alterations in cognitive function. It is possible that the slopes of the cognitive trajectories are, indeed, equal in these 2 groups, and that the cognitive trajectories start to separate significantly only after the incident coronary heart disease event compromising the cerebral vascular function. However, it might as well be that there actually are subtle differences in the cognitive functions that have remained undetectable due to methodological limitations. The methods widely used to measure cognitive function in clinical context might have limited sensitivity to capture the delicate alterations in cognitive function that are considered to be within the range of normal cognitive functioning. Therefore, the lack of differences in cognitive function between the 2 groups prior to coronary heart disease found in the present study might reflect the same lack of sensitive cognitive measurement methods. This highlights the need for wider discussion on the used cognitive measurement methods not only in a scientific, but also in a clinical context.
The effect sizes of incident coronary heart disease on cognitive function reported in the study by Xie et al. (6) are relatively small, but are still significant even with the selection bias present in the study. The attrition analyses showed that the nonparticipants had higher levels of several cardiovascular risk factors and poorer cognitive function than the participants who remained within the study. Considering this, the actual effect sizes would have been larger if not diluted by the selection bias. Furthermore, even if the effect sizes are small, they are worrisome given that even a small decline in cognitive function might have wide ramifications both at the individual and societal level. At the individual level, cognitive decline causes comprehensive loss of function and difficulties in activities of daily living, leading to increased need for help and even institutional care. Therefore, with the increasing numbers of elderly people due to the constantly aging population, even slight alterations in cognitive function might cause an exponentially increased burden on health care and health economics. These outlooks highlight the importance of the findings from the study by Xie et al. (6), as their results point out the need for active monitoring of cognitive function and decline in the population with coronary heart disease to adopt all means to avoid premature cognitive aging of this at-risk population.
Even though the exact mechanisms behind the associations still need further studies to be fully elucidated, the present findings highlight the role of cardiovascular risk factors and cardiovascular health as crucial determinants of cognitive trajectories in later life. Coronary heart disease might be a critical factor for the slope of the cognitive trajectory to meet the cut-off level for clinical cognitive impairment prematurely and to simultaneously reduce the amount of cognitively vital years. Finally, before the manifestation of the clinical coronary heart disease event, the affected individuals have usually been exposed to long-term cardiovascular risk burden predisposing to the clinical endpoints. Even if preventing the occurrence of risk factors (i.e., primordial prevention) or lowering established risk factor levels (i.e., primary prevention) would be the most optimal options to prevent or postpone the clinical cognitive impairment, it is crucial to identify specific at-risk populations for targeted secondary and tertiary prevention as done in the present study by Xie et al. (6). Given that the found associations are causal, the present results suggest that interventions targeted at risk factors for coronary heart disease would additionally not only target the risk factors for cognitive decline, but also the possible trigger affecting the slope of cognitive trajectory (i.e., coronary heart disease). Untangling the complex network of cardiovascular risk factors, cardiovascular diseases, and cognitive decline would eventually translate into better cardiovascular and cognitive health.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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