Weight loss is associated with rapid striatal dopaminergic degeneration in Parkinson's disease

Introduction: Weight loss in Parkinson's disease (PD) is associated with poorer clinical outcomes and rapid disease progression. However, it is unclear whether a longitudinal association between weight loss and striatal dopaminergic degeneration exists. Methods: Using data from 171 PD patients in the Parkinson's Progression Markers Initiative (PPMI) cohort, we investigated longitudinal associations of change in body mass index (BMI) with striatal dopaminergic activity on ¹²³ I-N-3-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ( ¹²³ I-FP-CIT) single positron emission computed tomography (SPECT). We defined BMI loss as a reduction in BMI value > 5% of baseline, and categorized the PD patients into 2 subgroups (patients with and without BMI loss). Linear mixed model (LMM) analysis was employed to compare the progression of striatal dopaminergic degeneration. Results: In LMM analyses, BMI values in PD patients were not correlated with clinical severities of parkinsonian motor deficits, cognitive impairment and depressive mood. However, BMI values were positively associated with changes in striatal ¹²³ I-FP-CIT binding over 24 months (caudate nucleus, estimate = 9.37 × 10 ⁻³ , p = 0.009; putamen, estimate = 7.04 × 10 ⁻³ , p = 0.031). Patients with BMI loss exhibited greater deterioration of striatal dopaminergic activity than those without (caudate nucleus, estimate = 3.35 × 10 ⁻³ , p = 0.008; putamen, estimate = 2.34 × 10 ⁻³ , p = 0.025). Conclusion: Our findings suggest a potential association between striatal dopaminergic activity with body weight or impairment in energy homeostasis. Body weight and its change may be a clinical biomarker reflecting striatal dopaminergic dysfunction in PD.