Healthy lifestyle prevents dementia in people with CVD

Individuals with cardiovascular disease (CVD) may derive more benefits from adherence to healthy lifestyle behaviours, which have been shown to be significantly associated with a reduced risk of dementia in a recent study.

"The observed associations may be partly explained by a reduction in systemic inflammation and the promotion of metabolic balance,” the investigators said.

Overall, 77,324 dementia-free participants with prevalent CVD from the UK Biobank were included in this prospective cohort study. A lifestyle score was created based on no current smoking, moderate alcohol intake, regular physical activity, healthy diet, adequate sleep duration, less sedentary behaviour, and frequent social contact.

The investigators examined the relationship between a healthy lifestyle and the risk of CVD-related dementia using Cox proportional hazard models. They then fitted mediation models to explore the underlying mechanisms driven by systemic inflammation, lipid profiles, liver/renal function, and blood pressure indices.

A total of 1,605 all-cause dementia (ACD) cases were recorded over a median follow-up of 12.43 years. These cases included 646 Alzheimer’s dementia (AD) and 427 vascular dementia (VaD). [Am J Clin Nutr 2025;121:511-521]

Healthy lifestyle scores showed a significant association with a reduced dementia risk. Specifically, individuals with 6–7 healthy lifestyle score had a 50-percent lower ACD risk (hazard ratio [HR], 0.50, 95 percent confidence interval [CI], 0.40–0.62), 20-percent lower AD risk (HR, 0.80, 95 percent CI, 0.58–1.10), and 70-percent lower VaD risk (HR, 0.30, 95 percent CI, 0.19–0.48) than those with 0–1 score.

These associations were significantly mediated by low-grade inflammatory markers and specific metabolic biomarkers, facilitating 1 percent to 11 percent of the association between healthy lifestyle factors and dementia risk.

“Our study additionally added the new evidence on mechanism underlying the associations that low-grade inflammatory markers and specific metabolic biomarkers were plausible pathways linking healthy lifestyle and dementia,” the investigators said. 

“These findings suggest that a multidomain lifestyle modification approach may be critical for preventing or delaying the onset of dementia, particularly among individuals with CVD,” they added.

Biological mechanism

Consistent with previous evidence, the current study found that neutrophil count, leukocyte count, lymphocyte count, and specific ratios in plasma whose increasing levels correlated with a higher dementia risk had a linear association with healthy lifestyle factors and partially mediated such relationship in individuals with CVD. [PLOS Med 2023;20:e1004135; Atherosclerosis 2020;301:37-43]

In addition, LDL cholesterol and APOA were also found to partially mediate the effect of post-CVD healthy lifestyle on dementia. Earlier studies showed that hypercholesterolemia, characterized by high levels of LDL cholesterol, played a role in brain neuropathology changes and intracerebral atherosclerosis. [J Neurol Neurosurg Psychiatry 2022;93:930-938; Atherosclerosis 2023;371:14-20]

A higher level of APOA, on the other hand, was found to be associated with a lower dementia risk, and use of an APOA mimetic peptide was noted to improve cognitive function and reduce amyloid burden in a mouse model of Alzheimer’s disease. [Neurobiol Dis 2009;34:525-534; EClinicalMedicine 2022;54:101695]

"It is thus believed that adopting a healthy lifestyle score might offer a foundation for reducing systemic inflammation, promoting metabolic balance, and ultimately reducing the risk of dementia,” the investigators said.