Fat mass loss correlates with faster disease progression in amyotrophic lateral sclerosis patients: Exploring the utility of dual-energy x-ray absorptiometry in a prospective study

Abstract

Background/objective: Weight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients to explore its utility as a biomarker of disease progression.

Methods: DEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

Results: The ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8).

Conclusion: Measurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.

Fig 1. Percentile distribution of ALS and PD cohorts at enrollment based on z scores compared to age, sex and race matched United States Population (USP).

The ALS cohort had significantly lower total lean mass index (A) and appendicular lean mass index (B) compared to the PD cohort and USP. The PD cohort had significantly higher appendicular lean mass compared to USP (B). Total fat mass index (C) and percent fat (D) were not different between ALS and PD cohorts and USP. P-values are derived from Wilcoxon signed-rank test of ALS cohort vs USP, PD cohort vs USP, and from Wilcoxon rank-sum test of ALS cohort vs PD cohort.

Fig 2. Baseline and change in DEXA measurements in ALS patients with two or more scans over the study period.

(A) ALSFRS-R, (B) Total Lean Mass Index, (C) Appendicular Lean Mass Index, (D) Total Fat Mass Index, and (E)) Percent Fat. Fast progressors are indicated with filled symbols and intermediate to slow progressors are indicated with open symbols. (F) Serial DEXA scans of patient A01 who was a fast progressor.

Fig 3. Correlation between ΔALSFRS-R with baseline and longitudinal DEXA measurements.

ΔALSFRS-R correlates significantly with (A) ΔTotal Fat Mass Index, (B) ΔPercent Fat and (C) baseline percent fat. The correlation is not significant with (D) ΔBMI, (E) ΔTotal Lean Mass Index and (F) ΔAppendicular Lean Mass Index.