A critical examination of the relationship between cardiovascular health,cognition,and dementia risk

As the older population grows, Alzheimer's disease (AD) rates are rising, ¹ making early detection and prevention crucial due to limited treatment options. Research has shown that improving cardiovascular health (CVH) in midlife can reduce the risk of AD.^2,3 The American Heart Association has updated its CVH measurement from Life's Simple 7 (LS7) to Life's Essential 8 (LE8), which now includes sleep duration along with blood pressure, glucose, cholesterol, body mass, diet, smoking, and physical activity. While higher LS7 scores have been linked to a lower risk of AD, the impact of mid-life LE8 on cognition is still unknown. Additionally, accurately tracking early cognitive changes in relation to LE8 may require more advanced neuropsychological methods, such as digital metrics, which traditional methods may not capture.

Yang and colleagues investigated the link between mid-life CVH using LE8 scores and cognitive performance, as well as the risk of dementia, in the Offspring cohort of the Framingham Heart Study (n = 1198). ⁴ Participants underwent health exams every 4 to 6 years, with ten exams conducted so far. Around the 9th exam, 1413 participants took a digital clock drawing test (dCDT). The study found that higher mid-life LE8 scores were associated with better dCDT performance and a lower risk of dementia. Ideal mid-life CVH was significantly related to higher dCDT scores compared to intermediate CVH. The dCDT showed a stronger relationship with mid-life LE8 scores than the conventional CDT. Additionally, for every 1 standard deviation increase in mid-life LE8 score, the risk of dementia decreased. The study also found that sex influenced the results, with higher LE8 scores linked to better dCDT performance in women but not in men. APOE ε4 status did not affect the results. These findings highlight the importance of mid-life CVH as a predictor of cognitive performance and dementia risk.

This study has several strengths, including a large sample size and longitudinal data, which provide a better understanding of CVH and cognitive decline with more generalizable results. It is one of the first investigations to examine the effect of LE8 on cognitive outcomes and incident dementia over time. This study contributes to the literature on CVH and dementia, particularly as LE8 includes sleep as a mid-life risk factor for cognitively normal individuals. Despite the Lancet commission not recognizing sleep as an official dementia risk factor, ⁵ many studies show a strong link between sleep issues and lower cognitive outcomes.^6–12 Importantly, this investigation used objective cognitive metrics, such as the dCDT, which captures detailed data through digital technology. Evaluating CVH in midlife, rather than late life, is advantageous because many neurobiological changes related to dementia occur 15–20 years before onset. This underscores the importance of early intervention to delay cognitive decline.

While this study has considerable strengths, it also has weaknesses: (1) The use of a single cognitive test (dCDT) rather than multiple neuropsychological methods limits comprehensiveness, as it does not cover verbal fluency, memory, attention, and delayed memory. (2) Despite strong follow-up data over 17.5 years, the relatively low number of incident dementia cases poses challenges for conducting specific analyses on CVH or LE8 strata, potentially limiting the implications of the association between LE8 and AD risk. (3) Limited stratified analysis between APOE and LE8 on cognition and incident AD was conducted. Although higher LE8 scores may be protective in both APOE ε4 carriers and non-carriers, additional research is needed to explore CVH risk and cognition in those with increased genetic risk. (4) The lack of diversity (mainly non-Hispanic White participants from affluent communities) limits the generalizability of the results, as cardiovascular risk factors may be more prevalent in underrepresented communities.^13,14 (5) Yang et al. analyzed the LE8 using standard deviations (SD) rather than absolute scores. While z-scores are a widely accepted metric in cognitive assessments, their application to lifestyle scoring introduces a level of abstraction, requiring readers to independently compute the actual values for interpretation.

A recent UK Biobank study found that high LE8 scores were associated with increased brain volume (hippocampus, grey matter) and reduced risk of mild cognitive impairment and various types of dementia, including AD and vascular dementia. ¹⁵ While Yang and colleagues also predicted similar dementia risk outcomes, their study did not include neuroimaging data. The UK Biobank had more thorough follow-up data, capturing more incident dementia cases, but lacked specific neuropsychiatric metrics. Future studies should include both neuroimaging and neuropsychiatric metrics to understand cognitive and neuroimaging outcomes in pre-clinical populations compared to those with clinical diagnoses.

Yang et al. demonstrated that higher mid-age LE8 scores were associated with better dCDT performance and could predict incident AD. Unlike Yang et al., two other studies that showed relationships between LE8 and cognitive tests were cross-sectional,^15,16 highlighting the value of Yang et al.'s longitudinal design. However, these cross-sectional studies used more comprehensive neuropsychiatric methods. Future research should incorporate comprehensive neuropsychiatric methods and longitudinal designs to capture transitions across the dementia spectrum and incident cases, elucidating differences in cognitive domains related to CVH. Furthermore, Yang et al.'s findings indicate that mid-age CVH affects digital cognitive performance differently in men and women, likely due to biological differences, thus, emphasizing the need for personalized prevention strategies that account for sex-specific health dynamics.

The inclusion of sleep in LE8 acknowledges its critical role in cognitive resilience and dementia risk, previously overlooked in LS7. Many studies have shown significant relationships between sleep-related issues and cognitive decline or dementia in older adults.^6–12 A recent study comparing LE8 and LS7 on cognitive health found that LE8, which includes sleep and revised metric scaling, outperformed LS7 in working memory but not in global cognitive performance. ¹⁷ This suggests the updated scaling in LE8 may be influential. The study highlights the need for consistent reporting of LE8 components and suggests using a more detailed sleep variable than self-reported sleep duration.

Overall, leveraging a large sample size and longitudinal data, the results from Yang et al. provide additional evidence of the relationship between CVH, cognitive outcomes, and dementia risk. Future studies in the field need to examine various cognitive domains with multiple neuropsychiatric batteries, including neuroimaging outcomes, a diverse patient sample, and considering the influence of genetic risks. Findings will provide additional rationale for personalized mitigation efforts aiming to increase CVH and reduce dementia.