TOPLINE: 

Risk of incident and vascular dementia was roughly 2 to 5 times higher, respectively, in individuals with advanced stages of cardiovascular-kidney-metabolic (CKM) syndrome, compared to those with less advanced disease, a new cohort study showed. Additionally, CKM stage progression raised the risk for Alzheimer's disease (AD) by more than 130%.

METHODOLOGY:

• A large cohort study included 2006-2010 data from the UK Biobank for nearly 240,000 participants aged 40-69 years without dementia. All were assigned stages of CKM syndrome (0-4) based on the presence of metabolic disorders, kidney disease, and cardiovascular disease.
• All-cause dementia and its subtypes were identified using hospital inpatient records and death registry data. More than 3500 participants developed dementia during a follow-up of 13.6 years, including 770 with vascular dementia and more than 1500 with AD.
• The analysis was adjusted for factors such as age, sex, smoking status, alcohol intake, physical activity, APOEε4 carrier status, and depressive symptoms.
• Brain MRI scans were used to assess structural brain volumes and white matter hyperintensities.

TAKEAWAY:

• Participants with incident dementia had a higher frequency of individual components of CKM, including metabolic disorders, kidney disease, and cardiovascular disease (all P  < .001). There was a dose-dependent risk for dementia, with stages 3 and 4 of CKM syndrome associated with an increased risk for all-cause dementia (hazard ratios [HRs], 1.74 and 1.92, respectively; P for both < .001) compared with stage 0. Advanced stages were also associated with reduced total brain volume, particularly in gray matter.
• Participants with stage 3 or 4 CKM syndrome had a fivefold increased risk for vascular dementia (HRs, 4.98 and 5.18, respectively; P for both < .001) and patients with stage 2 syndrome had a twofold increased risk (HR, 2.05; P = .02) compared with those with stage 0 syndrome.
• Stage progression during follow-up was associated with a 130% increased risk for incident AD, compared with stable low to intermediate stages (HR, 2.30; P = .02).
• Early stages of CKM syndrome were more strongly associated with increased dementia risk in individuals younger than 60 years, compared to their older peers (P for interaction < .001); and advanced stages were more strongly linked to all-cause dementia in women than in men (P = .01).

IN PRACTICE:

"These results suggest that an individualized assessment of whole CKM syndrome stratification should be conducted for young patients who have entered CKM syndrome staging and that lifestyle interventions or secondary prevention measures should be actively adopted to reduce the occurrence of dementia," the investigators wrote.

SOURCE:

The study was led by Heng Zhang, MD, PhD, of Shandong Provincial Hospital Affiliated with Shandong First Medical University in Jinan, China. It was published online on March 10 in The American Journal of Geriatric Psychiatry.

LIMITATIONS: 

A1c levels were used as a proxy for fasting glucose levels because blood glucose was not measured in a strict fasting state. Dementia and its subtypes were identified from hospital records and death registries rather than biomarker levels, potentially resulting in underdiagnosis or misclassification due to dementia's diagnostic complexity. Additionally, given the observational study design, residual confounding factors may have been present. 

DISCLOSURES:

The study was funded by the Natural Science Foundation of Shandong Province, the National Key R&D Program of China's Ministry of Sciences and Technology, the Brain Science and Brain-Like Intelligence Technology Research Projects of China, the National Natural Science Foundation of China, and the Shandong Provincial Hospital Research Incubation Fund. The investigators reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.