Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects.

BACKGROUND: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. MATERIAL AND METHODS: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. RESULTS: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. CONCLUSION: Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.

Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease.

BACKGROUND AND PURPOSE: Glymphatic dysfunction may play a significant role in the development of neurodegenerative diseases. We aimed to evaluate the association between glymphatic dysfunction and the risk of malignant event/clinical milestones in Parkinson disease (PD). METHODS: This study included 236 patients from August 2014 to December 2020. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was calculated as an approximate measure of glymphatic function. The primary outcomes were four clinical milestones including recurrent falls, wheelchair dependence, dementia, and placement in residential or nursing home care. The associations of DTI-ALPS with the risk of clinical milestones were examined using multivariate Cox proportional hazards regression models. Then, logistic regression was repeated using clinical variables and DTI-ALPS index individually and in combination of the two to explore the ability to distinguish patients who reached clinical milestones within a 5-year period. RESULTS: A total of 175 PD patients with baseline DTI-ALPS index and follow-up clinical assessments were included. A lower DTI-ALPS was independently associated with increased risk of recurrent falls, wheelchair dependence, and dementia. Additionally, in 103 patients monitored over 5 years, a logistic regression model combining clinical variables and DTI-ALPS index showed better performance for predicting wheelchair dependence within 5 years than a model using clinical variables or DTI-ALPS index alone. CONCLUSIONS: Glymphatic dysfunction, as measured by the DTI-ALPS index, was associated with increased risk of clinical milestones in patients with PD. This finding implies that therapy targeting the glymphatic system may serve as a viable strategy for slowing down the progression of PD.

Cholinergic basal forebrain system degeneration underlies postural instability/gait difficulty and attention impairment in Parkinson's disease.

BACKGROUND AND PURPOSE: The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system. METHODS: A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free-water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses. RESULTS: Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006). CONCLUSIONS: Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive-motor interaction.

Radiolysis of crown ether-ionic liquid systems: identification of radiolytic products and their effect on the removal of Sr(2+) from nitric acid.

The quantitative analysis and identification of the radiolytic products of dicyclohexano-18-crown-6 (DCH18C6), 4',4''(5'')-di-tert-butyldicyclohexano-18-crown-6 (DtBuCH18C6) and benzo-18-crown-6 (B18C6) in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide ([C4mim][NTf2]) ionic liquid after irradiation were performed for the first time. It was found that the yield for radiolytic destruction of DCH18C6 and DtBuCH18C6 was less than that for B18C6. The main radiolytic products were identified as substituted crown ethers formed between crown ether and active radicals such as methyl, trifluoromethyl, butyl, and [C4mim]˙ radicals generated during the irradiation of the crown ether-[C4mim][NTf2] system. The radiation effect on the Sr(2+) partitioning of the crown ether-[C4mim][NTf2] system shows further that DCH18C6-[C4mim][NTf2] and DtBuCH18C6-[C4mim][NTf2] still have good extractability for Sr(2+) after irradiation. The extraction ability of DCH18C6-[C4mim][NTf2] and DtBuCH18C6-[C4mim][NTf2] system for Sr(2+) decreased by 14.4% and 18.2% even at 500 kGy, respectively.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease.

BACKGROUND: Rest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear. METHODS: This study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases. RESULTS: The fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC. CONCLUSION: ET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.

α-Radiolysis of ionic liquid irradiated with helium ion beam and the influence of radiolytic products on Dy3+ extraction.

Helium ion (He(+)) beam produced by a heavy ion linear accelerator was used to simulate α-rays for studying the radiation effect on 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid ([C4mim][NTf2]). The water-soluble radiolytic products of [C4mim][NTf2] under He(+) beam irradiation were analysed, and it was found that they were similar to those by γ-ray irradiation, but their amount was much less than that by γ-ray irradiation, which was attributed to the recombination of [C4mim][NTf2] radical cations in track by high linear energy transfer (LET) radiations of the He(+) beam. The extracting behaviour of Dy(3+) using irradiated [C4mim][NTf2] in combination with alkylated bis-triazinyl-pyridine (CA-BTP) was assessed, and found that the influence of He(+) beam on the extraction was less than that of γ-ray irradiation. In addition, radiolytic products have a different influence on Dy(3+) extraction at different doses; Dy(3+) partitioning decreases at 50 kGy due to the protonation of CA-BTP and the inhibition of cation exchange mechanism by radiation-formed hydrogen ions. The abnormal increase of Dy(3+) partitioning at 100 kGy is mainly attributed to the precipitation formed between Dy(3+) and radiolytic products (F(-) and SO3(2-)).