Presence of neurofilament light chain linked to sleep, cognition in Parkinson’s disease

Key takeaways:

• 31 patients, with and without mild cognitive impairment, underwent overnight polysomnogram with blood draw for biomarkers.
• Neurofilament light chain levels were elevated in those with MCI by morning.

DENVER — Cognitive impairment in Parkinson’s is a mitigating factor for presence of blood-based biomarkers during sleep as indicator of disease progression, according to a poster at the American Academy of Neurology annual meeting.

“The glymphatic system is very active during sleep and we’re looking to see if sleep could be some sort of intervention for people with Parkinson’s disease,” Caileigh Dintino, BS, a research assistant in the Parkinson’s and Movement Disorders Center at Virginia Commonwealth University, told Healio.

Prior research suggests sleep disturbances in PD can contribute to disease progression and increase risk of dementia, but it is unknown whether disrupted sleep in PD alters neuroinflammatory and neurodegenerative biomarkers, which typically indicate disease progression and cognitive decline.

Dintino and colleagues aimed to investigate whether sleep in PD is associated with changes in blood-based biomarker levels such as neurofilament light chain, over the course of a single night.

Their study included 31 individuals with PD (mean age 67.4±6.0 years; 58% male), including 23 with normal cognition (52.1% female, mean age 67.4 ±6.0 years) and eight with mild cognitive impairment (87.5% male, mean age 68.4 ±6.6 years). All patients underwent an overnight polysomnogram with blood draws twice during the session, once at 8 p.m. and once at 6:30 a.m.

All participants also submitted to a full cognitive testing battery. Mild cognitive impairment (MCI) was defined by Z score on any two tests among five categories: executive function, memory, language, attention, visuospatial).

Plasma samples were analyzed using Meso Scale Discovery immunoassays for neuroinflammatory biomarkers interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-a), as well as the U-PLEX assay for alpha-synuclein.

Neurofilament light chain (NfL), which is released from axons upon injury or neuronal death, was measured using Quanterix Simoa assays, while T-tests were employed to compare overnight changes in biomarker levels. Subsequent correlations were tested with Pearson coefficients and a significance threshold of P < 0.05.

Dintino and colleagues reported that morning NfL levels were 16.5% higher in those with PD and MCI (PM: 13.70 ±4.15, AM: 16.38 ±7.79; P = 0.043), but not significantly different for those without cognitive issues (PM: 17.24 ±7.88, AM: 18.82 ±7.93; P = 0.091).

Morning levels of TNF-a were also elevated in the PD-MCI (PM: 1.83 ±0.88, AM: 1.86 ±0.87; P = 0.02) population but not for those without MCI (PM: 1.65 ±0.54, AM: 1.71 ±0.5; P = 0.38).

“Sleep is a big complaint [among those with Parkinson’s disease],” Dintino said. “Harnessing sleep, as a way to not only to improve quality of life, but to eventually slow disease progression ... could be life-changing for these people.”