Biological sex and age-associated changes in muscle and brain health in Chronic Obstructive Pulmonary Disease: A large cross-sectional study

Abstract

Background: Biological sex plays a role in systemic features of patients with Chronic Obstructive Pulmonary Disease (COPD). We investigated whether male and female COPD patients show distinct trajectories in muscle and brain health decline during aging.

Methods: In total 228 patients (age >50 years) with stable COPD (GOLD: II-IV) were stratified into four groups based on their sex and age (50-70 years vs ≥70 years). Body composition (DXA), muscle strength (dynamometry), cognitive function and well-being (assessments and questionnaires), and risk factors of poor systemic health were analyzed in these groups.

Results: Body weight and lean mass remain unchanged with aging. The ≥70 years males showed higher visceral adipose tissue and lower muscle strength whereas females showed lower fat mass and fat-free mass index, and worse cognitive performance compared with their younger counterparts (P < 0.04). In males, lower physical activity was associated with higher visceral adipose tissue and lower muscle function, whereas poor cognition was associated with low O₂ saturation. In females, lower muscle function was associated with higher age, dyspnea and lower caloric intake and physical activity, whereas mood disturbance and poor cognition were associated with smoking pack years (P < 0.05).

Conclusion: Aging in male COPD patients is characterized by metabolic syndrome features and muscle weakness whereas aging in female COPD patients is associated with weight loss, sarcopenia, and cognitive decline. The observed systemic changes were influenced by different combinations of risk factors in male and female COPD patients. Our findings indicate that sex-specific therapies need to be considered when treating older patients with COPD.

Keywords: COPD; aging; cognition; muscle function; risk factors; sex differences.

Figure 1

Subgroup differences of main outcomes. (A) Body mass index. (B) Lean soft tissue. (C) Fat mass. (D) Visceral adipose tissue. Open bars are for the men, and closed bars are for the women. Green bars are for the men and women 50–70 years of age, and orange bars are for the men and women ≥70 years of age.

Figure 2

Subgroup differences of muscle and cognitive functions. (A) Maximal handgrip strength. (B) Peak leg torque extension. (C) Trail making test B time. (D) MoCA. Open bars are for the men, and closed bars are for the women. Green bars are for the men and women 50–70 years of age, and orange bars are for the men and women ≥70 years of age. MoCA, Montreal Cognitive Assessment.

Figure 3

A heat map of the correlations between risk factors and main outcome variables. The color bar on the right shows a gradual color change from dark green (Pearson correlation coefficient (r) = 1) to white (Pearson correlation coefficient (r) = 0) and to dark orange (Pearson correlation coefficient (r) = −1). Each r value is presented in the cells in the graph. Empty cells are |r| < 0.001. P values of the Pearson correlation coefficient (r) can be found in the supplemental files (Tables S3 and S4). 6MWT, 6‐Minute Walk Test; FEV₁, forced expiratory volume in 1 s predicted; MoCA, Montreal Cognitive Assessment; MRC dyspnea scale; Medical ResearchCouncil dyspnea scale.