Abstract
Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson’s disease (PD), but the underlying mechanisms remain unclear.Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk.Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF).Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (Ptrend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D < 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule.Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies within neurons (Ascherio and Schwarzschild, 2016; Armstrong and Okun, 2020)
Our results showed that the serum 25(OH)D levels of PD patients were lower than in the healthy controls (HC) group (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001) (Table 2)
The severity of PD was evaluated according to the Hoehn and Yahr Staging Scale (H&Y) stage (1–5), and when the PD patients were divided into early (H&Y stage = 1– 2.5) and middle or late PD (H&Y stage = 3–5), there was a significant trend showing that as the HY stage worsened, the 25(OH)D levels became lower
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies within neurons (Ascherio and Schwarzschild, 2016; Armstrong and Okun, 2020). Environmental factors, especially vitamin D (VD), are thought to be related to the occurrence of PD (Shen and Ji, 2015; Wang et al, 2016). Accumulating evidence from in vivo and in vitro animal studies suggest that VD plays a neuroprotective and nutritional role in dopaminergic neurons by regulating neurotrophic factors, inducing the removal of αsynuclein, maintaining calcium homeostasis, as well as regulating oxidative stress and the immune response (Aureli et al, 2014; Calvello et al, 2017; Phillipson, 2017; Pertile et al, 2018). VD deficiency may not be a consequence of PD, but may be related to the occurrence and development of the disease (Newmark and Newmark, 2007; Peterson, 2014). Many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson’s disease (PD), but the underlying mechanisms remain unclear
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