Cardiometabolic Diseases Linked With Increased Dementia RIsk For Younger, Female Patients

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Patients with a single cardiometabolic disease have an approximate 48% greater risk of developing all-cause dementia compared with those without a cardiometabolic disease.

Data in a study published in BMC Public Health showed that the correlation between cardiometabolic multimorbidity and dementia was stronger for younger patients and those who were female. Investigators said that more research and data will be needed for these specific populations to confirm the correlation.1

Diabetes, Cardiovascular, Obesity, Cardiometabolic, Pharmacy, Dementia, Alzheimer disease

Patients with a single cardiometabolic disease have an approximate 48% greater risk of developing all-cause dementia compared with those without a cardiometabolic disease. | Image Credit: Atthapon - stock.adobe.com

“The findings of our study align with those of previous studies showing that cardiometabolic multimorbidity significantly increases the risk of dementia,” the study authors said.1 “However, these studies did not specifically distinguish the subtypes of dementia, relying on cognitive scale scores or using only incident dementia as the outcome measures.”

Previous research has shown that cardiometabolic disease (CMD) is linked with dementia since CMD induces chronic systemic inflammation, causing proinflammatory molecules to cross the blood-brain barrier. This has investigators hypothesizing that there is a pathophysiological mechanism that links CMD multimorbidity with dementia, either with an inflammatory or metabolic marker, according to the investigators.1

In recent data, investigators identified underlying neural mechanisms between obesity and cognition for adults, indicating obesity trajectories influenced brain morphology, function, and cognition: low-stable, moderate-stable, high-stable, increasing, and decreasing. Patients who were obese had a greater risk of developing age-related cognitive decline, vascular dementia, and mild cognitive impairment, among other neurodegenerative diseases.2

In another study, investigators found that glucagon-like peptide-1 receptor agonists, a known drug class used for diabetes, obesity, and cardiovascular diseases, were associated with statistically significant reductions in all-cause mortality. Because of the targets and indications of the medications, this could further link dementia with CMDs.3

In the current study, investigators aimed to explore the association between CMDs and dementia for both the population and subset of patients—including those stratified by age, sex, smoking status, drinking status, ethnicity, education, moderate activity levels, and sleep—as well as explore the inflammatory and metabolic mediators that could play a role in the association.1

Investigators in the UK Biobank were used, which included individuals enrolled from 2006 to 2010 at 22 centers in the UK. Detailed data were collected on demographic covariates, lifestyle, disease diagnostics, and blood tests. Patients with preexisting dementia or Alzheimer disease were excluded. For CMDs, investigators included heart disease, stroke, and type 2 diabetes, and dementia included all-cause dementia, Alzheimer disease, and vascular dementia. The primary outcome included all-cause dementia, and secondary outcomes included Alzheimer disease and vascular dementia.1

Investigators included 287,748 people in the study overall, with 267,574 who did not have a CMD, 18,007 who had 1, and 2167 who had CMD multimorbidity. The median age of all individuals included was 58 years, and those with CMD multimorbidity were older than those who were CMD-free or had 1 CMD. Approximately 52.4% of patients were female. Patients who had 3 CMDs had the highest Townsend deprivation index and were more frequently former smokers. Hypertension was common across the groups and depression rates were higher for those with type 2 diabetes.1

Over a median duration of 15.17 years of follow-up, 5057 patients experienced all-cause dementia, with 2353 having Alzheimer disease and 1048 having vascular dementia. Further, the incidence rates per 1000 person-years were 1.01 in the CMD-free group compared with 5.84 in the CMD multimorbidity group for all-cause dementia, 0.49 and 1.63 for Alzheimer disease, respectively, and 0.18 and 2.51 for vascular dementia, respectively. After accounting for variables, patients with a single CMD had a 48% greater risk of developing all-cause dementia compared with those without a CMD.1

As for the subgroup analysis, most groups did not differ from the main analysis, except for age, sex, moderate activity duration, and sleep duration, according to the investigators. They reported positive correlations between CMD multimorbidity and all-cause mortality and Alzheimer disease for patients who were younger than 60 years or female. Further, for all-cause dementia and vascular dementia, there was a significant increase in risk for patients who slept less than 6 hours a night or had a low duration of moderate activity.1

“The broader age range in our study may capture a more diverse genetic and environmental landscape, potentially highlighting the role of genetic factors in younger individuals,” the study authors concluded.1 “A substantial amount of data indicates that interventions during middle age are crucial, but some risk factors originate at the societal level and persist throughout one’s life."

READ MORE: Neurology Resource Center

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REFERENCES
1. Zhang J, Huang X, Ling Y, et al. Associations of cardiometabolic multimorbidity with all-cause dementia, alzheimer's disease, and vascular dementia: a cohort study in the UK biobank. BMC Public Health. 2025;25(1):2397. Published 2025 Jul 7. doi:10.1186/s12889-025-23352-5
2. Gallagher A. Data Show Neural Mechanisms Between Obesity and Cognition. Drug Topics. April 10, 2025. Accessed July 8, 2025. https://www.drugtopics.com/view/data-show-neural-mechanisms-between-obesity-and-cognition
3. Gallagher A. GLP-1 Therapy May Reduce Dementia Risk. Drug Topics. April 8, 2025. Accessed July 8, 2025. https://www.drugtopics.com/view/glp-1-therapy-may-reduce-dementia-risk
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