Effects of Dihydropyridines on the Motor and Cognitive Outcomes of Patients with Parkinson's Disease.

BACKGROUND: Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD). OBJECTIVE: This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD. METHODS: We classified 476 patients with drug-naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN-; n = 50) and patients with hypertension treated without DHP (HTN+/DHP-; n = 50) or with DHP (HTN+/DHP+; n = 50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa-equivalent dose, respectively. Using Kaplan-Meier analyses, we compared the risks of levodopa-induced dyskinesia, wearing off, and dementia-free survival during the 5.06 years of the mean follow-up period. The Cox regression model determined the independent effects of DHPs on dementia conversion. RESULTS: Dopamine transporter availability in all striatal subregions was comparable between the HTN-, HTN+/DHP-, and HTN+/DHP+ groups. The risks of levodopa-induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa-equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP- (Bonferroni-corrected Plog-rank  = 0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087-0.668; P = 0.006). CONCLUSIONS: DHPs may be associated with better long-term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society.

Association of cholesterol level with dopamine loss and motor deficits in Parkinson disease: A cross-sectional study.

BACKGROUND AND PURPOSE: Cholesterol is vital in neuronal function; however, the influence of cholesterol levels on parkinsonism is unclear. This study investigated the relationship between baseline total cholesterol (TC) levels, dopamine loss, and motor symptoms in drug-naïve Parkinson disease (PD). METHODS: This cross-sectional study enrolled 447 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging. Multivariate linear regression was used to investigate the effect of cholesterol levels on Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) total score and each subscore after adjusting for the covariates. An interaction analysis was performed to examine the interaction between TC levels and statin use on the UPDRS-III scores. RESULTS: No significant correlation was found between TC levels and DAT availability after adjusting for potential confounders. Multivariate linear regression showed that TC levels were significantly and negatively associated with the UPDRS-III total score (ß = -0.116, p = 0.013) and bradykinesia subscore (ß = -0.145, p = 0.011). Dichotomized analysis according to TC levels showed that TC levels were significantly associated with UPDRS-III total score, and rigidity, bradykinesia, and axial subscores only in the low TC group. There was an interaction effect between TC levels and statin use for the axial subscores (ß = -0.523, p = 0.025). Subgroup analysis showed that TC levels were significantly and negatively associated with the axial subscore in statin users; however, no association was found in statin nonusers. CONCLUSIONS: This study suggests that TC levels affect parkinsonian motor symptoms, especially in subjects with low cholesterol status, whereas the severity of axial motor symptoms is negatively associated with TC levels only in statin users.

Effects of statins on dopamine loss and prognosis in Parkinson's disease.

Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease by blocking cholesterol biosynthesis but also for the potential neuroprotective agents during neurological disorders due to their pleiotropic effects. In this study, we investigate whether the previous use of statins affect baseline nigrostriatal dopamine loss at the time of diagnosis and longitudinal motor and cognitive outcomes in patients with Parkinson's disease. Five hundred drug-naïve patients with Parkinson's disease who underwent dopamine transporter imaging were classified into two groups according to the prior use of statins: patients with and without statin use. Multivariate linear regression was used to determine intergroup differences in dopamine transporter availability. We evaluated the longitudinal changes in levodopa-equivalent dose and dementia conversion between the groups using a linear mixed model and survival analysis, respectively. In addition, mediation analysis was applied to examine the effect of total cholesterol. Patients with Parkinson's disease treated with statins had a lower baseline dopamine transporter availability in the anterior (2.13 ± 0.55 versus 2.37 ± 0.67; P = 0.002), posterior (1.31 ± 0.43 versus 1.49 ± 0.54; P = 0.003) and ventral putamina (1.40 ± 0.39 versus 1.56 ± 0.47; P = 0.002) than that in matched patients with Parkinson's disease without statins. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a previous treatment with statins remained significantly and independently associated with more severely decreased dopamine transporter availability in the anterior putamen (Beta = -0.140, P = 0.004), posterior putamen (Beta = -0.162, P = 0.001) and ventral putamen (Beta = -0.140, P = 0.004). A linear mixed model revealed that patients with Parkinson's disease being treated with statins had a faster longitudinal increase in levodopa-equivalent dose than those without. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statins (hazard ratio, 2.019; 95% confidence interval, 1.108-3.678; P = 0.022) than those without. Mediation analyses revealed that the effect of statin treatment on baseline dopamine transporter availability and longitudinal outcome was not mediated by total cholesterol levels. This study suggests that statin use may have a detrimental effect on baseline nigrostriatal dopamine degeneration and long-term outcomes in patients with Parkinson's disease.

Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson's disease.

Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1. In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson's disease. We classified 697 drug naive patients with de novo Parkinson's disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson's disease being treated with (n = 54) or without DPP4 inhibitors (n = 85), and non-diabetic patients with Parkinson's disease (n = 558). Diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had a higher baseline dopamine transporter availability in the anterior (2.56 ± 0.74 versus 2.10 ± 0.50; P = 0.016), posterior (1.83 ± 0.69 versus 1.40 ± 0.50; P < 0.001), and ventral putamina (1.72 ± 0.58 versus 1.35 ± 0.37; P = 0.001) than that in diabetic patients with Parkinson's disease without DPP4 inhibitors. Additionally, diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had higher dopamine transporter availability in the posterior putamen than that in non-diabetic patients with Parkinson's disease (1.83 ± 0.69 versus 1.43 ± 0.59; P < 0.001). After adjusting for age, sex, disease duration, and vascular risk factors, linear regression models showed that a prior treatment of DPP4 inhibitors remained independently and significantly associated with dopamine transporter availability in the anterior (ß = -0.186, P = 0.012; ß = -0.207, P = 0.003), posterior (ß = -0.336, P < 0.001; ß = -0.286, P < 0.001), and ventral putamina (ß = -0.204, P = 0.005; ß = -0.250, P < 0.001). A linear mixed model revealed that the diabetic group with Parkinson's disease being treated with DPP4 inhibitors had a slower longitudinal increase in levodopa-equivalent dose than the other groups (P = 0.003). Survival analyses showed that the rate of levodopa-induced dyskinesia was significantly lower in the diabetic group with a prior treatment with DPP4 inhibitors than the diabetic group without DPP4 inhibitors (hazard ratio = 0.194, P = 0.037). These findings suggest that DPP4 inhibitors may confer beneficial effects on the baseline nigrostriatal dopamine degeneration and long-term motor outcomes in diabetic patients with Parkinson's disease and may extend its role into non-diabetic patients with Parkinson's disease.

Diffusion tensor imaging-based pontine damage as a degeneration marker in synucleinopathy.

The pons is one of the earliest affected regions in patients with synucleinopathies. We aimed to investigate the diagnostic value of measuring pontine damage using diffusion tensor imaging (DTI) in these patients. We enrolled 49 patients with Parkinson's disease (PD), 16 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), 23 patients with multiple system atrophy (MSA), and 39 healthy controls in this study. All the participants underwent high-resolution T1-weighted imaging and DTI. Mean diffusivity (MD) and fraction anisotropy (FA) values in the pons were calculated to characterize structural damage. The discriminatory power of pontine MD and FA values to differentiate patients with synucleinopathies from healthy controls was examined using receiver operating characteristics (ROC) analyses. Compared to healthy controls, patients with PD, iRBD, and MSA had increased MD values and decreased FA values in the pons, although no correlation was observed between these DTI measures and disease severity. The ROC analyses showed that MD values in the pons had a fair discriminatory power to differentiate healthy controls from patients with PD (area under the curve [AUC], 0.813), iRBD (AUC, 0.779), and MSA (AUC, 0.951). The AUC for pontine FA values was smaller than that for pontine MD values when differentiating healthy controls from patients with PD (AUC, 0.713; p = 0.054) and iRBD (AUC, 0.686; p = 0.045). Our results suggest that MD values in the pons may be a useful marker of brain stem neurodegeneration in patients with synucleinopathies.

White Matter Hyperintensities, Dopamine Loss, and Motor Deficits in De Novo Parkinson's Disease.

BACKGROUND: White matter hyperintensities, prevalent in patients with Parkinson's disease (PD), significantly affect parkinsonian motor symptoms. The objective of this study was to investigate the relationship between white matter hyperintensities and nigrostriatal dopamine depletion and their interaction or mediating effects on motor symptoms in patients with drug-naive early-stage PD. METHODS: This cross-sectional study enrolled 501 patients with de novo PD who initially underwent [18 F] N-(3-fluoropropyl)-2ß-carbonethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography and brain magnetic resonance imaging scans between April 2009 and September 2015 in a tertiary-care university hospital. We quantified dopamine transporter availability in each striatal subregion and assessed the severity of periventricular and lobar white matter hyperintensities using the Scheltens scale. The relationship between white matter hyperintensities, dopamine transporter availability in the posterior putamen, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was assessed using multivariate linear regression and mediation analyses. RESULTS: Periventricular and frontal white matter hyperintensities were generally associated with dopamine transporter availability in striatal subregions after adjusting for age at symptom onset, sex, disease duration, and vascular risk factors. There was an interaction effect between periventricular white matter hyperintensities and dopamine transporter availability in the posterior putamen for the axial motor score. The effect of white matter hyperintensities on UPDRS total score and bradykinesia subscore was indirectly mediated by dopamine transporter availability in the posterior putamen, whereas the axial sub-score was directly affected by white matter hyperintensities. CONCLUSIONS: This study suggests that the detrimental effect of white matter hyperintensities on parkinsonian motor symptoms is more relevant and independent for axial motor impairments in the status of mildly decreased striatal dopamine transporter availability. © 2021 International Parkinson and Movement Disorder Society.

Identifying the Functional Brain Network of Motor Reserve in Early Parkinson's Disease.

BACKGROUND: The severity of motor symptoms in Parkinson's disease (PD) does not always correlate with the degree of nigral dopaminergic neuronal loss. Individuals with greater motor reserve may have milder motor signs than their striatal dopamine loss. In this study, we explored the functional brain network associated with motor reserve in early-stage PD. METHODS: We analyzed 134 patients with de novo PD who underwent dopamine transporter scans and resting-state functional magnetic resonance imaging. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We applied network-based statistic analysis to identify the functional brain network associated with the measure of motor reserve (ie, motor reserve network). We also assessed the effect of motor reserve network connectivity strength on the longitudinal increase in levodopa-equivalent dose during the 2-year follow-up period. RESULTS: Network-based statistic analysis identified the motor reserve network composed of the basal ganglia, inferior frontal cortex, insula, and cerebellar vermis at a primary threshold of P value 0.001. Patients with an increased degree of functional connectivity within the motor reserve network had greater motor reserve. There was a significant interaction between the motor reserve network strength and time in the linear mixed model, indicating that higher motor reserve network strength was associated with slower longitudinal increase in levodopa-equivalent dose. CONCLUSIONS: The present study revealed the functional brain network associated with motor reserve in patients with early-stage PD. Functional connections within the motor reserve network are associated with the individual's capacity to cope with PD-related pathologies. © 2020 International Parkinson and Movement Disorder Society.

Motor Cerebellar Connectivity and Future Development of Freezing of Gait in De Novo Parkinson's Disease.

OBJECTIVE: To investigate the role of motor cerebellar connectivity in future development of freezing of gait, because it is a complex network disorder in Parkinson's disease (PD). METHODS: We recruited 26 de novo patients with PD who experienced freezing of gait within 5 years from magnetic resonance imaging acquisition (vulnerable PD group), 61 patients with PD who had not experienced freezing of gait within 5 years (resistant PD group), and 27 healthy control subjects. We compared the resting state functional connectivity between the motor cerebellum and the whole brain between the groups. In addition, we evaluated the relationship between motor cerebellar connectivity and freezing of gait latency. RESULTS: The vulnerable PD group had increased functional connectivity between the motor cerebellum and parieto-occipito-temporal association cortices compared with the control group or the resistant PD group. Connectivity between lobule VI and the right superior parietal lobule, right fusiform gyrus, and left inferior temporal gyrus; between lobule VIIb and the right superior parietal lobule, right hippocampus, and right middle temporal gyrus; and between lobule VIIIb and the bilateral fusiform gyri, right middle occipital gyrus, and bilateral parietal lobes was inversely proportional to freezing of gait latency. The freezing of gait latency-related cortical functional connectivity from the motor cerebellum was also significantly higher in the vulnerable PD group compared with the control group, as well as the resistant PD group. CONCLUSIONS: The data suggest that the motor cerebellar functional connectivity with the posterior cortical areas play an important role in future development of freezing of gait in PD. © 2020 International Parkinson and Movement Disorder Society.

Unusual cortical symptoms of dural arteriovenous fistula mimicking transient ischemic attack.

The clinical presentation of dural arteriovenous fistula (DAVF) can vary. A 47-year-old man complained of transient difficulty playing badminton and speech disturbance for 10 minutes. His symptoms were suspected to be visuomotor coordination deficit similar to optic ataxia and anomic aphasia. Magnetic resonance imaging and angiography revealed vasogenic edema and perfusion delay in the left temporo-occipital area and an abnormal connection between the left occipital artery and transverse sinus. Transverse sinus DAVF was diagnosed by conventional cerebral angiography. We believe that this is the unique case of DAVF manifested as visuomotor coordination deficit suspected optic ataxia and anomic aphasia.

On-Demand Droplet Capture and Release Using Microwell-Assisted Surface Acoustic Waves.

We demonstrate an acoustofluidic platform that uses surface acoustic waves (SAWs) for the facile capture of droplets inside microwells and their on-demand release. When the ac signal applied to the device is tuned to modulate the location of the SAW, the SAW-based acoustic radiation force retracts or pushes the droplets into or out of one of three microwells fabricated inside a microchannel to selectively capture or release the droplet.

Particle Separation inside a Sessile Droplet with Variable Contact Angle Using Surface Acoustic Waves.

A sessile droplet of water carrying polystyrene microparticles of different diameters was uniformly exposed to high frequency surface acoustic waves (SAWs) produced by an interdigitated transducer (IDT). We investigated the concentration behavior of the microparticles as the SAWs generated a strong acoustic streaming flow (ASF) inside the water droplet and exerted a direct acoustic radiation force (ARF) on the suspended particles, the magnitude of which depended upon the particle diameter. As a result of the ARF, the microparticles were concentrated according to their diameters at different positions inside the sessile droplet placed in the path of the SAW, right in front of the IDT. The microparticle concentration behavior changed as the sessile droplet contact angle with the substrate was varied by adding surfactant to the water or by gradually evaporating the water. The positions at which the smaller and larger microparticles were concentrated remained distinguishable, even at very different experimental conditions. The long-term exposure of the droplets to the SAWs was accompanied by the gradual evaporation of the carrier fluid, which dynamically changed the droplet contact angle as well as the concentration of particles. Complete evaporation of the fluid left behind several concentrated yet separated clusters of particles on the substrate surface. The effect of the droplet contact angle on particles' concentration behavior and consequent separation of particles has been uniquely studied in this SAW-based report.

A Pumpless Acoustofluidic Platform for Size-Selective Concentration and Separation of Microparticles.

We have designed a pumpless acoustofluidic device for the concentration and separation of different sized particles inside a single-layered straight polydimethylsiloxane (PDMS) microfluidic channel. The proposed device comprises two parallel interdigitated transducers (IDTs) positioned underneath the PDMS microchannel. The IDTs produce high-frequency surface acoustic waves that generate semipermeable virtual acoustic radiation force field walls that selectively trap and concentrate larger particles at different locations inside the microchannel and allow the smaller particles to pass through the acoustic filter. The performance of the acoustofluidic device was first characterized by injecting into the microchannel a uniform flow of suspended 9.9 µm diameter particles with various initial concentrations (as low as 10 particles/mL) using a syringe pump. The particles were trapped with ∼100% efficiency by a single IDT actuated at 73 MHz. The acoustofluidic platform was used to demonstrate the pumpless separation of 12.0, 4.8, and 2.1 µm microparticles by trapping the 12 and 4.8 µm particles using the two IDTs actuated at 73 and 140 MHz, respectively. However, most of the 2.1 µm particles flowed over the IDTs unaffected. The acoustofluidic device was capable of rapidly processing a large volume of sample fluid pumped through the microchannel using an external syringe pump. A small volume of the sample fluid was processed through the device using a capillary flow and a hydrodynamic pressure difference that did not require an external pumping device.

Acoustic Wave-Driven Functionalized Particles for Aptamer-Based Target Biomolecule Separation.

We developed a hybrid microfluidic device that utilized acoustic waves to drive functionalized microparticles inside a continuous flow microchannel and to separate particle-conjugated target proteins from a complex fluid. The acoustofluidic device is composed of an interdigitated transducer that produces high-frequency surface acoustic waves (SAW) and a polydimethylsiloxane (PDMS) microfluidic channel. The SAW interacted with the sample fluid inside the microchannel and deflected particles from their original streamlines to achieve separation. Streptavidin-functionalized polystyrene (PS) microparticles were used to capture aptamer (single-stranded DNA) labeled at one end with a biotin molecule. The free end of the customized aptamer15 (apt15), which was attached to the microparticles via streptavidin-biotin linkage to form the PS-apt15 conjugate, was used to capture the model target protein, thrombin (th), by binding at exosite I to form the PS-apt15-th complex. We demonstrated that the PS-apt15 conjugate selectively captured thrombin molecules in a complex fluid. After the PS-apt15-th complex was formed, the sample fluid was pumped through a PDMS microchannel along with two buffer sheath flows that hydrodynamically focused the sample flow prior to SAW exposure for PS-apt15-th separation from the non-target proteins. We successfully separated thrombin from mCardinal2 and human serum using the proposed acoustofluidic device.

Transfer of Microparticles across Laminar Streams from Non-Newtonian to Newtonian Fluid.

Engineering inertial lift forces and elastic lift forces is explored to transfer microparticles across laminar streams from non-Newtonian to Newtonian fluid. A co-stream of non-Newtonian flow loaded with microparticles (9.9 and 2.0 µm in diameter) and a Newtonian carrier medium flow in a straight rectangular conduit is devised. The elastic lift forces present in the non-Newtonian fluid, undeterred by particle-particle interaction, successfully pass most of the larger (9.9 µm) particles over to the Newtonian fluid. The Newtonian fluid takes over the larger particles and focus them on the equilibrium position, separating the larger particles from the smaller particles. This mechanism enabled processing of densely suspended particle samples. The method offers dilution-free (for number densities up to 10,000 µL(-1)), high throughput (6700 beads/s), and highly efficient (>99% recovery rate, >97% purity) particle separation operated over a wide range of flow rate (2 orders of magnitude).

Generation of Dynamic Free-Form Temperature Gradients in a Disposable Microchip.

Temperature gradients (TGs) provide an effective approach to controlling solvated molecules and creating spatiotemporally varying thermal stimuli for biochemical research. Methods developed to date for generating TGs can only create a limited set of static temperature profiles. This article describes a method for establishing dynamic free-form TGs in polydimethylsiloxane (PDMS) as well as in gases and liquids in contact with the PDMS. The heating mechanism relies on the efficient acoustic absorption by the PDMS of high-frequency (5-200 MHz) surface acoustic waves (SAWs). MATLAB-aided actuation of a transducer enabled the generation and propagation of SAWs in a controlled fashion, which permitted spatiotemporal control over the temperature in the PDMS microstructures. This technique is exploited to perform one-shot high-resolution melting (HRM) analysis to detect single nucleotide polymorphisms (SNPs) in DNA. The experimental results displayed a 10-fold higher resolution and an enhanced signal-to-noise ratio compared to the results obtained using a conventional real-time PCR machine.

Microchannel anechoic corner for size-selective separation and medium exchange via traveling surface acoustic waves.

We demonstrate a miniaturized acoustofluidic device composed of a pair of slanted interdigitated transducers (SIDTs) and a polydimethylsiloxane microchannel for achieving size-selective separation and exchange of medium around polystyrene particles in a continuous, label-free, and contactless fashion. The SIDTs, deposited parallel to each other, produce tunable traveling surface acoustic waves (TSAWs) at desired locations, which, in turn, yield an anechoic corner inside the microchannel that is used to selectively deflect particles of choice from their streamlines. The TSAWs with frequency fR originating from the right SIDT and propagating left toward the microchannel normal to the fluid flow direction, laterally deflect larger particles with diameter d1 from the hydrodynamically focused sample fluid that carries other particles as well with diameters d2 and d3, such that d1 > d2 > d3. The deflected particles (d1) are pushed into the top-left corner of the microchannel. Downstream, the TSAWs with frequency fL, such that fL > fR, disseminating from the left SIDT, deflect the medium-sized particles (d2) rightward, leaving behind the larger particles (d1) unaffected in the top-left anechoic corner and the smaller particles (d3) in the middle of the microchannel, thereby achieving particle separation. A particle not present in the anechoic corner could be deflected rightward to realize twice the medium exchange. In this work, the three-way separation of polystyrene particles with diameters of 3, 4.2, and 5 µm and 3, 5, and 7 µm is achieved using two separate devices. Moreover, these devices are used to demonstrate multimedium exchange around polystyrene particles ∼5 µm and 7 µm in diameter.

Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

Differential effects of cholesterol levels on cognition according to body mass index in Parkinson's disease.

BACKGROUND: Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson's disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. METHODS: This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion. RESULTS: TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (ß = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (ß = - 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014). CONCLUSIONS: This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.

Biofilm formation and exopolysaccharide (EPS) production by Cronobacter sakazakii depending on environmental conditions.

Biofilm matrices are formed largely of extracellular polymeric substance (EPS). This study was conducted to investigate biofilm formation and EPS production by Cronobacter sakazakii under various conditions (media, nutrition, and relative humidity (RH)) by quantification of EPS and cell populations, Field Emission Scanning Electron Microscope (FE-SEM), and colony observation. Various agar media conditions (TSA without dextrose (W/D), M9 minimum salt medium (MSM) agar, and M9 MSM agar with 3% glucose, 3% NaCl, 3% Tween 80, 3% sucrose, and adjusted to pH 5 with HCl) were prepared. C. sakazakii biofilm formed on the surface of stainless steel coupons (SSCs) immersed in TSB W/D and M9 MSM with or without 0, 1, 3, and 5% sucrose and subsequently exposed to various RH levels (23, 43, 68, 85, and 100%). EPS production by C. sakazakii on TSA W/D was significantly higher than that on other media after 1 and 2 days. However, C. sakazakii ATCC 12868 produced the highest levels of EPS (209.18 ± 16.13 and 207.22 ± 4.14 µg/mL after 1 and 2 days, respectively) on M9 MSM agar with 3% sucrose. Regarding C. sakazakii ATCC 12868 biofilm formed on the surface of SSCs immersed in M9 MSM with 0, 1, 3, and 5% sucrose and subsequently exposed to various RHs, populations were significantly different among the various RHs and sucrose concentrations, and EPS production was significantly higher (4.69 mg/L) compared to other sucrose concentrations (0%:0.71 mg/L and 1%:0.98 mg/L), except for M9 MSM with 3% sucrose (2.97 mg/L) (P ≤ 0.05). From these results, biofilm formation and EPS production by C. sakazakii differed depending on the nutrient or environmental conditions provided to the cells.

Occipital Amyloid Deposition Is Associated with Rapid Cognitive Decline in the Alzheimer's Disease Continuum.

BACKGROUND: Clinical significance of additional occipital amyloid-ß (Aß) plaques in Alzheimer's disease (AD) remains unclear. OBJECTIVE: In this study, we investigated the effect of regional Aß deposition on cognition in patients on the AD continuum, especially in the occipital region. METHODS: We retrospectively reviewed the medical record of 208 patients with AD across the cognitive continuum (non-dementia and dementia). Multivariable linear regression analyses were performed to determine the effect of regional Aß deposition on cognitive function. A linear mixed model was used to assess the effect of regional deposition on longitudinal changes in Mini-Mental State Examination (MMSE) scores. Additionally, the patients were dichotomized according to the occipital-to-global Aß deposition ratio (ratio ≤1, Aß-OCC- group; ratio >1, Aß-OCC+ group), and the same statistical analyses were applied for between-group comparisons. RESULTS: Regional Aß burden itself was not associated with baseline cognitive function. In terms of Aß-OCC group effect, the Aß-OCC+ group exhibited a poorer cognitive performance on language function compared to the Aß-OCC- group. High Aß retention in each region was associated with a rapid decline in MMSE scores, only in the dementia subgroup. Additionally, Aß-OCC+ individuals exhibited a faster annual decline in MMSE scores than Aß-OCC- individuals in the non-dementia subgroup (ß= -0.77, standard error [SE] = 0.31, p = 0.013). CONCLUSION: The present study demonstrated that additional occipital Aß deposition was associated with poor baseline language function and rapid cognitive deterioration in patients on the AD continuum.