Nutritional frailty and the incidence of depression and anxiety among middle-aged and older adults: A prospective cohort study

Background & aims: Frailty has been linked to an increased risk of mental disorders. However, little is known about the impact of nutritional frailty, a crucial phenotype of frailty, on depression and anxiety. We aimed to examine the prospective associations between nutritional frailty and the incidence and progression of depression and anxiety among middle-aged and older adults. Methods: Data were obtained from a large prospective cohort study with over 500,000 participants. Nutritional frailty was defined as the copresence of physical frailty (assessed by weight loss, exhaustion, low physical activity level, slowness, and weakness) and nutritional imbalance (assessed by body mass index, skeletal muscle index, and sodium, potassium, and iron intake). Depression, anxiety, and their comorbidity were identified via the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision, on the basis of the primary or secondary diagnosis. We performed Cox proportional hazards models to investigate the associations between nutritional frailty and incident depression, anxiety, and their comorbidity. Multistate models were used to examine how nutritional frailty influences transitions from a baseline state to single mental disorders, their comorbidity, and mortality. Results: We included 176,987 participants with a mean age of 56.1 years (SD 8.0), of whom 2648 (1.5%) had nutritional frailty at baseline. During a median follow-up of 12.2 years, 4794 (2.7%) developed depression, 6081 (3.4%) developed anxiety, and 1610 (0.9%) developed both conditions. Individuals with nutritional frailty had a significantly greater risk of developing depression, anxiety, and their comorbidity than robust individuals and those with physical frailty and nutritional imbalance (depression: nutritional frailty HR 3.21 [95% CI 2.77-3.73]; physical frailty 3.11 [2.70-3.58]; nutritional imbalance 1.19 [1.11-1.28]; anxiety: 2.25 [1.93-2.63], 2.17 [1.87-2.51], 1.20 [1.13-1.28]; comorbidity: 3.69 [2.92-4.66], 3.43 [2.74-4.28], 1.31 [1.15-1.50]), even after multivariable adjustment. Baseline nutritional frailty adversely impacts transitions from a baseline state to single mental disorders (depression: 2.89 [2.49-3.36],anxiety: 1.82 [1.54-2.16]) and death (1.95 [1.71-2.22]), from single mental disorders to their comorbidity (depression: 1.96 [1.32-2.89]; anxiety 1.78 [1.17-2.71]), and from comorbidity to death (2.04 [1.07-3.91]). Conclusions: Nutritional frailty is an independent risk factor for incident depression, anxiety, and their comorbidity and adversely influences the progression of these conditions among middle-aged and older adults. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).