Objective: Determine if plasma lipid levels can serve as a surrogate biomarker of future onset of RBD symptoms or nighttime sleep burden in patients with Parkinson’s disease (pwPD).

Background: REM sleep behavior disorder (RBD) is a common prodromal feature of Parkinson’s disease (PD)[1] and lower levels of apolipoprotein A1 have been correlated with earlier onset of PD[2]. It has been hypothesized that lipid synthesis may be affected by sleep disturbances, as the apnea–hypopnea index (AHI) has been correlated with increased triglycerides, lower HDL, and apolipoprotein A1 (ApoA1) levels in people without PD[3]. However, the association between plasma lipid levels and sleep related morbidity has not been explored in pwPD.

Method: Using Parkinson’s Progression Markers Initiative (PPMI) data, we investigated the association between baseline (BL) and 1-year change in plasma lipid levels in PD subjects without RBD (RBD Questionnaire score < 4) at baseline (cohort 1), controlled for nighttime sleep burden by excluding subjects with MDS-UPDRS Part I (PI) Item (I)7 score > 2 at baseline. We compared this group to those with RBD at baseline (RBD-Q > 5) (cohort 2) over 5-years of follow-ups, using Welch’s t-test. We then examined the development of nighttime sleep burden or RBD over 5-years of follow-ups in cohort 1, using generalized linear modeling. Subjects with missing lipids and outcomes were excluded.

Results: Table 1 contains participant demographics. There are significant differences between BL to 1-year magnitude of change in triglycerides (p = 0.016), HDL (p = 0.018), and ApoA1 (p = 0.011) in subjects from cohort 2 compared to patients from cohort 1 who developed RBD over a 5-year period (Table 2). There was no predictive utility of baseline, or 1-year changes in plasma lipids for future incidence of RBD symptoms, since 61 out of 62 subjects developed symptoms by 5-years. Baseline LDL levels were lower among subjects who developed nighttime sleep burden (n = 30) compared to those who did not (n = 49) in a 5-year period (97.20 ± 28.39 vs. 113.47 ± 36.70 p = 0.0305) (Table 3).

Conclusion: Variable changes in triglycerides, HDL, and ApoA1 levels are associated with development of RBD symptoms after PD diagnosis and could inform us about the interaction between lipid metabolism and sleep disturbance in PD. LDL levels may also serve as a predictive lipid biomarker of future development of nighttime sleep burden.

Table 1.

Table 2.

Table 3.

References: 1. Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, Oertel WH, Arnulf I, Ferini-Strambi L, Puligheddu M, Antelmi E, Cochen De Cock V, Arnaldi D, Mollenhauer B, Videnovic A, Sonka K, Jung KY, Kunz D, Dauvilliers Y, Provini F, Lewis SJ, Buskova J, Pavlova M, Heidbreder A, Montplaisir JY, Santamaria J, Barber TR, Stefani A, St Louis EK, Terzaghi M, Janzen A, Leu-Semenescu S, Plazzi G, Nobili F, Sixel-Doering F, Dusek P, Bes F, Cortelli P, Ehgoetz Martens K, Gagnon JF, Gaig C, Zucconi M, Trenkwalder C, Gan-Or Z, Lo C, Rolinski M, Mahlknecht P, Holzknecht E, Boeve AR, Teigen LN, Toscano G, Mayer G, Morbelli S, Dawson B, Pelletier A. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019 Mar 1;142(3):744-759. doi: 10.1093/brain/awz030. PMID: 30789229; PMCID: PMC6391615.

2. J. K. Qiang, Y. C. Wong, A. Siderowf, H. I. Hurtig, S. X. Xie, V. M. ‐Y. Lee, J. Q. Trojanowski, D. Yearout, J. B. Leverenz, T. J. Montine, M. Stern, S. Mendick, D. Jennings, C. Zabetian, K. Marek, A. S. Chen‐Plotkin, Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Annals of Neurology 74, 119–127 (2013).

3. Bikov, A., Lazar, Z., Horvath, P., Tarnoki, D. L., Tarnoki, A. D., Fesus, L., Horvath, M., Meszaros, M., Losonczy, G., & Kunos, L. (2019). Association between serum lipid profile and obstructive respiratory events during REM and Non-REM Sleep. Lung, 197(4), 443–450.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-lipids-as-potential-biomarkers-for-progression-of-sleep-disturbances-in-parkinsons-disease/