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March 6, 2026Neuropsychiatric Disease and Treatment0 citationsOpen Access

Joint Associations of Cardiometabolic Multimorbidity and Depressive Symptoms on Cognitive Function Among Chinese Middle-Aged and Older Adults

ZXZhiyao XinLWLi WangKWKeying Wu

Key Result

Co-existing cardiometabolic multimorbidity and depressive symptoms were associated with a 1.31 standard deviation lower global cognitive composite score compared to participants without either condition (β = -1.31, 95% CI -2.11 to -0.52, p=0.001) in Chinese middle-aged and older adults.

Key Points

  • This study investigates how cardiometabolic multimorbidity (CMM) and depressive symptoms affect cognitive function in middle-aged and older adults.
  • Cross-sectional design involving 341 middle-aged and older adults.
  • Assessment of cognitive function using composite z-scores from TMT-A, TMT-B, and AFT.
  • Evaluation of depressive symptoms using the CES-D scale.
  • Linear regression analysis to determine associations between variables.
  • CMM linked to lower cognitive scores (β = −0.37).
  • Higher number of chronic diseases correlates with greater cognitive impairment (β = −1.08).
  • Depressive symptoms negatively affect cognitive scores (β = −0.66).
  • Individuals with both CMM and depressive symptoms had the lowest cognitive scores (β = −1.31).

Study Design

Type

Cross-Sectional (n=341)

Multicenter

No

Structured PICO

Does the co-occurrence of cardiometabolic multimorbidity and depressive symptoms worsen cognitive function in Chinese middle-aged and older adults?

P
Population
341 middle-aged and older adults (≥45 years) from a memory clinic in Shenzhen, China, mean age 62.4 years, 52.8% male. Exclusions: major head trauma, intracranial surgery, rheumatic/blood diseases, severe infections, mental illness affecting cognitive assessment, intracranial space-occupying lesion, acute cerebral vascular disorders.
I
Intervention
Cardiometabolic multimorbidity (CMM, defined as ≥2 cardiometabolic diseases including diabetes, stroke, and heart disease) and depressive symptoms (CES-D score >20)
C
Comparator
Individuals without cardiometabolic diseases and without depressive symptoms
O
Outcome
Global cognitive function measured by a composite z-score based on performance on the Trail Making Test-A (TMT-A), Trail Making Test-B (TMT-B), and Animal Verbal Fluency Test (AFT)surrogate

The co-occurrence of cardiometabolic multimorbidity and depressive symptoms has a synergistic detrimental effect on cognitive function in middle-aged and older adults.

Main Result

Effect estimate: β = -1.31 for combined CMM and depressive symptoms vs neither (95% CI 95% CI = -2.11 to -0.52)

p-value: p=0.001

Limitations

  • Small sample size, particularly of subgroup with both CMM and depressive symptoms (n=3), limiting stability of interaction estimates
  • Cross-sectional design precludes causal inference
  • Participants recruited exclusively from memory clinic, possible selection bias
  • Cognitive assessment focused primarily on sustained attention and executive function, not comprehensive
  • Regional sampling from Guangdong Province may limit generalizability
  • small subgroup with both CMM and depressive symptoms (n=3)
  • unstable estimate requiring validation in larger studies

Abstract

Purpose: Cognitive decline in middle-aged and older adults globally is a pressing health concern, linked to two significant factors: cardiometabolic multimorbidity (CMM) and depressive symptoms. This study aimed to investigate the independent, joint, and interactive effects of CMM and depressive symptoms on cognitive function in Chinese middle-aged and older adults. Patients and Methods: A total of 341 middle-aged and older adults were enrolled from the memory clinic at Qianhai Shekou Free Trade Zone Hospital in Shenzhen between May 2022 and June 2025 for this cross-sectional study. A composite z-score, computed based on performance on the Trail Making Test-A (TMT-A), Trail Making Test-B (TMT-B), and Animal Verbal Fluency Test (AFT), served as the measure of global cognition. CMM describes a constellation of at least two cardiometabolic diseases, including diabetes, stroke, and heart disease. Assessment of depressive symptoms was conducted using the Center for Epidemiological Studies-Depression Scale (CES-D). Linear regression was used. Results: This study enrolled 341 individuals over 45 years of age. The sample had a mean age of 62.4 years (SD 9.1), and 52.8% were male. A significant link was observed between CMM and lower global cognitive scores ( β = − 0.37, 95% CI = − 0.57 to − 0.17). A higher number of CMDs was positively associated with the severity of cognitive impairment ( β=− 1 .08, 95% CI=− 0 .28 to − 0.08). Depressive symptoms were inversely associated with cognitive scores ( β=− 0 .66, 95% CI=− 1 .03 to − 0.30). Participants with co-existing CMM and depressive symptoms exhibited the lowest cognitive scores ( β=− 1 .31, 95% CI=− 2 .11 to − 0.52) relative to those without either condition. This pattern remained consistent in all subgroups. Conclusion: In this cross-sectional study, the association between co-existing CMM and depressive symptoms and poorer cognitive function highlights the need for integrated management of physical and mental health to preserve cognition in Chinese middle-aged and older adults. Keywords: cardiometabolic multimorbidity, depressive symptoms, cognitive function, middle-aged and older adults

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Cite This Study

Xin et al. (2026) conducted a cross-sectional in Chinese middle-aged and older adults (≥45 years) with cognitive complaints, including subgroups with cardiometabolic multimorbidity and/or depressive symptoms (n=341). Cardiometabolic multimorbidity (CMM) and depressive symptoms vs. Participants without CMM or depressive symptoms was evaluated on Global cognitive function composite z-score based on Trail Making Test-A, Trail Making Test-B, and Animal Verbal Fluency Test (β = -1.31 for combined CMM and depressive symptoms vs neither, 95% CI 95% CI = -2.11 to -0.52, p=0.001). Co-existing cardiometabolic multimorbidity and depressive symptoms were associated with a 1.31 standard deviation lower global cognitive composite score compared to participants without either condition (β = -1.31, 95% CI -2.11 to -0.52, p=0.001) in Chinese middle-aged and older adults.

synapsesocial.com/papers/69aa7077531e4c4a9ff5a4b3https://doi.org/10.2147/ndt.s569145
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