Plasma Acylcarnitines as Metabolic Signatures of Declining Health-Related Quality of Life Measure in Community-Dwelling Older Adults: A Combined Cross-sectional and Longitudinal Pilot Study

Author:

Ng Ted Kheng Siang1,Wee Hai Ning2ORCID,Ching Jianhong23,Kovalik Jean-Paul2,Chan Angelique W456,Matchar David Bruce467

Affiliation:

1. Edson College of Nursing and Health Innovation, Arizona State University , USA

2. Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School , Singapore

3. KK Research Centre, KK Women’s and Children’s Hospital , Singapore

4. Program in Health Services and Systems Research, Duke-National University of Singapore Medical School , Singapore

5. Department of Sociology, Faculty of Arts and Social Sciences, National University of Singapore , Singapore

6. Center for Aging, Research and Education, Duke-National University of Singapore Medical School , Singapore

7. Department of Medicine (General Internal Medicine), Duke University School of Medicine , USA

Abstract

Abstract Background Health-related quality of life (HRQoL) measures are predictors of adverse health outcomes in older adults. Studies have demonstrated cross-sectional associations between HRQoL measures and blood-based biochemical markers. Acylcarnitines (ACs) are a class of metabolites generated in the mitochondria and are predictive of multiple geriatric syndromes. Changes in ACs reflect alterations in central carbon metabolic pathways. However, the prospective relationship between plasma ACs and declining HRQoL has not been examined. This study aimed to investigate both cross-sectional and longitudinal associations of baseline ACs with baseline and declining EuroQol-5 Dimension/EuroQol Visual Analogue Scale (EQ-5D/EQ-VAS) in community-dwelling older adults. Methods One hundred and twenty community-dwelling older adults with EQ-5D/EQ-VAS measurements at baseline and follow-up were included. We quantified ACs at baseline using targeted plasma metabolomics profiling. Multivariate regressions were performed to examine cross-sectional and longitudinal associations between the measures. Results Cross-sectionally, ACs showed no significant associations with either EQ-5D index or EQ-VAS scores. Longitudinally, multiple baseline short-chain ACs were significantly and inversely associated with declining EQ-5D index score, explaining up to 8.5% of variance in the decline. Conclusions Within a cohort of community-dwelling older adults who had high HRQoL at baseline, we showed that higher levels of short-chain ACs are longitudinally associated with declining HRQoL. These findings reveal a novel association between central carbon metabolic pathways and declining HRQoL. Notably, dysregulation in mitochondrial central carbon metabolism could be detected prior to clinically important decline in HRQoL, providing the first evidence of objective biomarkers as novel predictors to monitor HRQoL in nonpharmacological interventions and epidemiology.

Funder

STaR Investigator

National Medical Research Council

Ministry of Education

National University of Singapore-Tsao Ageing Research Initiative, Singapore

Publisher

Oxford University Press (OUP)

Subject

Geriatrics and Gerontology,Aging

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