Association of Cerebrospinal Fluid Neurofilament Heavy Protein Levels With Clinical Progression in Patients With Parkinson Disease

Abstract

IMPORTANCENeurofilament light in biofluids has been associated with progression of Parkinson disease (PD), but the association between neurofilament heavy (NfH) and progression of PD has not been investigated. OBJECTIVE To evaluate the associations of cerebrospinal fluid (CSF) NfH (cNfH) levels and motor and cognitive progression in PD. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the Parkinson Progression Marker Initiative ranging from June 2010 to November 2018. Participants were recruited from 24 participating sites worldwide (United States, Europe, and Australia). Data were analyzed from October 20 to December 18, 2021. EXPOSURES Concentrations of NfH in CSF. MAIN OUTCOMES AND MEASURES The primary outcomes were Movement Disorder Societysponsored revisions of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III; scores range from 0 to 132, with higher scores indicating worse motor function, and Montreal Cognitive Assessment (MoCA); scores range from 0 to 30, with higher scores indicating better cognitive function. The associations of cNfH levels and longitudinal change in MDS-UPDRS-Part-III and MoCA were examined using linear mixed-effects models with PD duration as the time scale. Partial correlation analysis was conducted to examine the associations of cNfH levels and α-synuclein, amyloid-β 1-42 (Aβ 42) , phosphorylated tau at threonine 181 position (P-tau), and total tau (T-tau) levels in CSF. RESULTS A total of 404 patients with PD (mean [SD] age, 61.7 [9.7] years; 263 were men [65.1%];within 2 years of diagnosis; Hoehn and Yahr <3) were included. Higher baseline cNfH levels were associated with greater increases in MDS-UPDRS Part-III (β = 0.39; 95% CI, 0.12-0.66; P = .003) and faster decreases in MoCA (β = −0.18; CI, −0.24 to −0.11; P < .001). Levels of cNfH were correlated with CSF levels of α-synuclein (Spearman r = 0.25; 95% CI, 0.15-0.34; P < .001), Aβ 42 (Spearman r = 0.18; 95% CI, 0.08-0.27; P < .001), P-tau (Spearman r = 0.25; 95% CI, 0.15-0.35; P < .001), and T-tau (Spearman r = 0.31; 95% CI, 0.21-0.40; P < .001) at baseline. CONCLUSIONS AND RELEVANCEHigher baseline cNfH levels were associated with faster motor and cognitive progression. This finding suggests that cNfH may be of some value for stratifying patients with PD who have different progression rates.

Association of Diabetes with Cardiovascular Calcification and All-Cause Mortality in Nephropathic Patients on Maintenance Hemodialysis Early: A Retrospective Cohort Study

“…Calcium and phosphorus disorders contribute to vascular calci cation. Previous research has revealed a favorable association between the degree of vascular calci cation and hyperphosphatemia, particularly in HD [25][26][27][28][29]. Nevertheless, several investigations have revealed no link between phosphorus and vascular calci cation in a metaanalysis [30].…”

Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View

“…The cytoskeleton of large projection neurons might be particularly prone to dysfunction, as suggested by the biochemical pathways of aggregation and displacement of axonal neurofilaments (Nf) proteins and the microtubule-associated protein tau, observed in motor neurons in ALS and pyramidal neurons in AD [ 184 ]. Moreover, axonopathy in cases of neurodegeneration, like AD [ 185 , 186 ], PD [ 187 , 188 ], and ALS [ 189 , 190 ], causes the release of phosphorylated neurofilament (pNf) into the cerebrospinal fluid (CSF), and subsequently into the blood. Thus, increased neurofilament light chain (NfL) in biofluids acts as a potential biomarker in NDDs like AD, PD, and ALS.…”

Access to Dietary Treatment for Inborn Errors of Metabolism: You Do Not Get What You Do Not Pay For

“…In China, a significant increase in blood phenylalanine levels was found in some centers when their social medical insurance reimbursement policy for special foods was canceled; levels were lowered when the policy was restored. 1 In the US, no uniform reimbursement policy exists, and each state has different strategies regarding medical foods for IEM. A 2013 survey 4 asked parents questions regarding insurance coverage for medical foods and foods modified to be low in protein and found that even though most children had insurance coverage, more than 10% had uncovered expenses for medical foods and nearly 60% of families using modified low-protein food had minimal support for use of these products.…”

“…5 Though new treatments for phenylketonuria have emerged, improving the likelihood of maintaining control of phenylalanine levels, the mainstay of treatment remains dietary restriction of phenylalanine. Wang et al 1 suggest that limiting access to medical foods results in diminished metabolic control of this condition. Our failure to assure access to these proven therapies limits the long-term potential for affected children and improving access may improve treatment efficacy.…”

“…The article by Wang et al suggests that adherence to treatments for (and resulting improvements in outcomes for) inborn errors of metabolism (IEM) treated by diet depend on access to care and availability of treatment. In this article, we learned what should be self-evident, and is repeated over and over around the world: if access to dietary treatments for rare IEM is not provided effectively, children do not receive adequate support for their care and families cannot adhere to recommended treatment strategies, which results in less successful management.…”