Hippocampal Subfield Integrity and Age-Driven Neural Correlates of Appetite Loss in Amyotrophic Lateral Sclerosis Publisher Pubmed



Ghaderi S ; Mohammadi S ; Kalra S
Source: Journal of Magnetic Resonance Imaging Published:2026

Abstract

Background: Appetite loss is a non-motor symptom in amyotrophic lateral sclerosis (ALS) linked to poorer prognosis. While the hippocampus regulates “meal memory”, a key cognitive modulator of eating behavior, its structural role in ALS-related appetite loss is unknown. Purpose: To determine if hippocampal subfield integrity influences appetite dysregulation in ALS and to evaluate the strength of neuroanatomical versus demographic factors. Study Type: Cross-sectional secondary analysis. Population: Thirty-two patients with ALS (mean age: 58.97 ± 8.91 years; 24 males) and 22 non-neurodegenerative controls (NNDc) (mean age: 53.86 ± 9.98 years; 16 males). Field Strength/Sequence: 3T; 3D T1-weighted magnetization-prepared rapid gradient-echo (MP2RAGE) and 3D T2-weighted turbo spin-echo (T2-SPACE) sequences. Assessment: Appetite was measured using the Council on Nutrition Appetite Questionnaire (CNAQ). Hippocampal subfield volumes (CA1, CA2/3, CA4/DG, stratum radiatum/lacunosum/moleculare [SRLM], subiculum) and asymmetry indices were segmented from T1w and T2w images using the HIPS automated pipeline. Statistical Tests: Analysis of Covariance (ANCOVA) (adjusting for age, sex, body mass index (BMI), total intracranial volume (TIV), and subfield volumes/asymmetry) and hierarchical multiple regression analyses were used. Significance was set at p < 0.05. Results: Patients with ALS (adjusted mean: 29.51 ± 0.53) had significantly lower adjusted CNAQ scores compared to controls (adjusted mean: 31.98 ± 0.66; mean difference: −2.47, partial η2 = 0.195). In the ANCOVA model, left SRLM volume was the only significant neuroanatomical covariate (F [1, 30] = 6.45, partial η2 = 0.177). However, hierarchical regression revealed that age was the only consistent independent predictor of CNAQ scores (B = −0.158), explaining the largest variance (ΔR2 = 0.165). Hippocampal volumes and asymmetry did not remain significant predictors after adjusting for age (left SRLM: p = 0.853; SRLM asymmetry: p = 0.868). Data Conclusion: Appetite loss is a non-motor symptom in ALS. While associated with lower left SRLM volume at the group level, appetite decline is more robustly and independently associated with advancing age. Evidence Level: 3. Technical Efficacy: 3. © 2025 International Society for Magnetic Resonance in Medicine.