An interpretable multiparametric radiomics model of basal ganglia to predict dementia conversion in Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) severely affects patients' prognosis, and early detection of patients at high risk of dementia conversion is important for establishing treatment strategies. We aimed to investigate whether multiparametric MRI radiomics from basal ganglia can improve the prediction of dementia development in PD when integrated with clinical profiles. In this retrospective study, 262 patients with newly diagnosed PD (June 2008-July 2017, follow-up >5 years) were included. MRI radiomic features (n = 1284) were extracted from bilateral caudate and putamen. Two models were developed to predict dementia development: (1) a clinical model-age, disease duration, and cognitive composite scores, and (2) a combined clinical and radiomics model. The area under the receiver operating characteristic curve (AUC) were calculated for each model. The models' interpretabilities were studied. Among total 262 PD patients (mean age, 68 years ± 8 [standard deviation]; 134 men), 51 (30.4%), and 24 (25.5%) patients developed dementia within 5 years of PD diagnosis in the training (n = 168) and test sets (n = 94), respectively. The combined model achieved superior predictive performance compared to the clinical model in training (AUCs 0.928 vs. 0.894, P = 0.284) and test set (AUCs 0.889 vs. 0.722, P = 0.016). The cognitive composite scores of the frontal/executive function domain contributed most to predicting dementia. Radiomics derived from the caudate were also highly associated with cognitive decline. Multiparametric MRI radiomics may have an incremental prognostic value when integrated with clinical profiles to predict future cognitive decline in PD.

Association of choroid plexus volume with motor symptoms and dopaminergic degeneration in Parkinson's disease.

BACKGROUND: The choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. This study aimed to investigate the association between CP volume (CPV), nigrostriatal dopaminergic degeneration and motor outcomes in Parkinson's disease (PD). METHODS: We retrospectively searched drug-naïve patients with early-stage PD who underwent dopamine transporter (DAT) scanning and MRI. Automatic CP segmentation was performed, and the CPV was calculated. The relationship between CPV, DAT availability and Unified PD Rating Scale Part III (UPDRS-III) scores was assessed using multivariate linear regression. We performed longitudinal analyses to assess motor outcomes according to CPV. RESULTS: CPV was negatively associated with DAT availability in each striatal subregion (anterior caudate, ß=-0.134, p=0.012; posterior caudate, ß=-0.162, p=0.002; anterior putamen, ß=-0.133, p=0.024; posterior putamen, ß=-0.125, p=0.039; ventral putamen, ß=-0.125, p=0.035), except for the ventral striatum. CPV was positively associated with the UPDRS-III score even after adjusting for DAT availability in the posterior putamen (ß=0.121; p=0.035). A larger CPV was associated with the future development of freezing of gait in the Cox regression model (HR 1.539, p=0.027) and a more rapid increase in dopaminergic medication in the linear mixed model (CPV×time, p=0.037), but was not associated with the risk of developing levodopa-induced dyskinesia or wearing off. CONCLUSION: These findings suggest that CPV has the potential to serve as a biomarker for baseline and longitudinal motor disabilities in PD.

Effects of Alzheimer's genetic risk scores and CSF biomarkers in de novo Parkinson's Disease.

Coexisting Alzheimer's disease (AD) pathology is common in Parkinson's disease (PD). However, the implications of genetic risk scores (GRS) for AD have not been elucidated in PD. In 413 de novo PD and 195 healthy controls from the Parkinson's Progression Marker Initiative database, the effects of GRS for AD (GRS-AD) and PD (GRS-PD) on the risk of PD and longitudinal CSF biomarkers and clinical outcomes were explored. Higher GRS-PD and lower baseline CSF α-synuclein were associated with an increased risk of PD. In the PD group, GRS-AD was correlated positively with CSF p-tau/Aß and negatively with CSF α-synuclein. Higher GRS-PD was associated with faster CSF p-tau/Aß increase, and GRS-AD and GRS-PD were interactively associated with CSF α-synuclein. In the PD group, higher GRS-AD was associated with poor visuospatial function, and baseline CSF p-tau/Aß was associated with faster cognitive decline. Higher GRS-PD was associated with better semantic fluency and frontal-related cognition and motor function given the same levels of CSF biomarkers and dopamine transporter uptake. Taken together, our results suggest that higher GRS-AD and CSF p-tau/Aß, reflecting AD-related pathophysiology, may be associated with cognitive decline in PD patients.

Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism.

OBJECTIVE: This study aimed to determine the pattern of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). METHODS: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(-)/LBD(-), AD(-)/LBD(+), AD(+)/LBD(-), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. RESULTS: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. INTERPRETATION: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853-863.

Swallowing Outcomes Following Voice Therapy in Multiple System Atrophy with Dysphagia: Comparison of Treatment Efficacy with Parkinson's Disease.

Difficulties with speech and swallowing occur in patients with Parkinsonism. Lee Silverman Voice Treatment (LSVT) is proven as an effective treatment for speech and swallowing function in idiopathic Parkinson's disease (IPD). The effect of LSVT on swallowing function in multiple system atrophy-cerebellar type (MSA-C) is unknown. We sought to determine LSVT's effect on swallowing function in MSA-C patients compared to IPD patients. LSVT-LOUD was performed on 13 patients with Parkinsonism (6 IPD and 7 MSA-C). Maximum phonation time (MPT), voice intensity, Speech Handicap Index-15 (SHI-15), Swallowing-Quality of Life (SWAL-QOL), National Institutes of Health-swallowing safety scale (NIH-SSS), and videofluoroscopic dysphagia scale (VDS) before and after LSVT were analyzed and reevaluated three months after treatment. The IPD and MSA-C groups showed significant improvements in overall speech and swallowing measures after LSVT. In particular, pharyngeal phase score and total score of VDS improved significantly in both groups. A two-way repeated-measure ANOVA revealed a significant main effect for time in the MPT, voice intensity, NIH-SSS, pharyngeal phase score and total score of VDS, psychosocial subdomain of SHI-15, and SWAL-QOL. The MSA-C group experienced less overall improvement in swallowing function, but the two groups had an analogous pattern of improvement. In conclusion, LSVT is effective for enhancing swallowing function, particularly in the pharyngeal phase, in both IPD and MSA-C patients. This study demonstrated that LSVT elicits significant improvements in MSA-C patients. We deemed LSVT to be an effective treatment for IPD and MSA-C patients who suffer from dysphagia.

Erratum.

[This corrects the article DOI: 10.1002/dad2.12177.].

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism.

Serum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was measured using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images. Higher serum uric acid levels exhibited a detrimental effect on NC, whereas a protective trend was observed in individuals with cognitive impairment. Interestingly, higher uric acid levels were associated with a slower decline in cognitive scores and brain metabolism in females with MCI, and this effect was found in APOE4 carriers, but not in non-carriers. Longitudinal AD-like patterns of brain metabolism on FDG-PET images also appeared to mediate the effects of baseline uric acid levels on longitudinal cognitive decline. In summary, higher serum uric acid may interact with APOE4 to alleviate longitudinal metabolic changes and cognitive decline in female MCI patients.

Interaction of CSF α-synuclein and amyloid beta in cognition and cortical atrophy.

INTRODUCTION: Lewy body-related pathology is commonly observed at autopsy in individuals with dementia, but in vivo biomarkers for α-synucleinopathy are lacking. METHODS: Baseline cerebrospinal fluid (CSF) biomarkers, polygenic risk score (PRS) for Parkinson's disease (PRS-PD) and Alzheimer's disease (PRS-AD), longitudinal cognitive scores, and magnetic resonance imaging were measured in 217 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear mixed models were used to find the relationship of CSF biomarkers and the PRS with cognition and cortical atrophy. RESULTS: Higher PRS-PD and PRS-AD were associated with lower CSF α-synuclein and amyloid beta (Aß), respectively. Lower CSF α-synuclein and the interaction of CSF α-synuclein and Aß were associated with lower cognitive scores and global cortical atrophy most prominently in the occipital cortex. DISCUSSION: Lower CSF α-synuclein could be a biomarker for α-synucleinopathy, and the simultaneous evaluation of CSF biomarkers for AD and CSF α-synuclein could reveal the independent and interactive effects on cognition and cortical atrophy.

Relationship between Hearing Loss and Dementia Differs According to the Underlying Mechanism.

BACKGROUND AND PURPOSE: The associations between hearing loss (HL) and the mechanisms underlying cognitive impairment (CI) remain unclear. We evaluated the effects of clinical factors, vascular magnetic resonance imaging (MRI) markers, and CI mechanisms on HL. METHODS: In total, 112 patients with CI (59% demented) and subjective HL prospectively underwent MRI, amyloid positron-emission tomography (PET), hearing evaluations, and neuropsychological tests including a language comprehension test. Patients were categorized into pure-Alzheimer's disease-related CI (ADCI), pure-Lewy-body disease-related CI (LBCI), mixed-ADCI/LBCI, and non-ADCI/LBCI groups based on clinical features and PET biomarkers. RESULTS: The risk of peripheral HL [defined as a pure-tone average (PTA) threshold >40 dB] was higher in the pure-LBCI group than in the pure-ADCI and mixed-ADCI/LBCI groups, and lower in the presence of ADCI. The non-ADCI/LBCI group had the most-severe vascular MRI markers and showed a higher risk of peripheral HL than did the pure-ADCI and mixed-ADCI/LBCI groups. While the pure-LBCI group had a higher risk of comprehension dysfunction than the pure-ADCI group regardless of the PTA and the score on the Korean version of the Mini Mental State Examination (K-MMSE), those in the pure-LBCI group even with a better K-MMSE score had a risk of comprehension dysfunction comparable to that in the mixed-ADCI/LBCI group due to a worse PTA. CONCLUSIONS: Peripheral HL could be associated with the absence of significant ß-amyloid deposition in patients with CI and characteristic of the pure-LBCI and non-ADCI/LBCI groups.

Effectiveness of Exercise on the Sequence Effect in Parkinson's Disease.

OBJECTIVE: To determine the benefits of motor training on the sequence effect (SE), an essential component of bradykinesia in Parkinson's disease (PD). METHODS: Seven patients with de novo PD participated in this study. The patients performed regular pentagon drawing tests and exercises during four visits. The first two visits occurred before the start of medication, and the last two visits occurred at least six months after the start of medication. We assessed the severity of bradykinesia and SE at each visit and compared the results before and after exercise in both the de novo and treatment conditions. RESULTS: In the de novo condition, the severity of bradykinesia significantly improved after motor training (p = 0.018), but it did not resolve and only showed a trend of improvement after treatment (p = 0.068). The severity of the SE decreased significantly in the drug-naïve condition (p = 0.028) but not after medication (p = 0.273). CONCLUSION: Our study suggests that regular motor training may be beneficial for the SE in PD.

Neural Correlates of Cognitive Performance in Alzheimer's Disease- and Lewy Bodies-Related Cognitive Impairment.

BACKGROUND: Clinicopathological studies have demonstrated that the neuropsychological profiles and outcomes are different between two dementia subtypes, namely Alzheimer's disease (AD) and Lewy bodies-related disease. OBJECTIVE: We investigated the neural correlates of cognitive dysfunction in patients with AD-related cognitive impairment (ADCI) and those with Lewy bodies-related cognitive impairment (LBCI). METHODS: We enrolled 216 ADCI patients, 183 LBCI patients, and 30 controls. Cortical thickness and diffusion tensor imaging analyses were performed to correlate gray matter and white matter (WM) abnormalities to cognitive composite scores for memory, visuospatial, and attention/executive domains in the ADCI spectrum (ADCI patients and controls) and the LBCI spectrum (LBCI patients and controls) separately. RESULTS: Memory dysfunction correlated with cortical thinning and increased mean diffusivity in the AD-prone regions, particularly the medial temporal region, in ADCI. Meanwhile, it only correlated with increased mean diffusivity in the WM adjacent to the anteromedial temporal, insula, and basal frontal cortices in LBCI. Visuospatial dysfunction correlated with cortical thinning in posterior brain regions in ADCI, while it correlated with decreased fractional anisotropy in the corpus callosum and widespread WM regions in LBCI. Attention/executive dysfunction correlated with cortical thinning and WM abnormalities in widespread brain regions in both disease spectra; however, ADCI had more prominent correlation with cortical thickness and LBCI did with fractional anisotropy values. CONCLUSIONS: Our study demonstrated that ADCI and LBCI have different neural correlates with respect to cognitive dysfunction. Cortical thinning had greater effects on cognitive dysfunction in the ADCI, while WM disruption did in the LBCI.

Unmet needs of people with Parkinson's disease: A cross-sectional study.

AIMS: To identify the type and extent of unmet needs in people with Parkinson's disease and to examine the impact of health locus of control and family support on these needs. DESIGN: A cross-sectional study. METHODS: This study was conducted from October 2015 - February 2016 in Korea. Data were collected through questionnaires focusing on unmet needs, health locus of control, family support and clinical features. RESULTS: Therapeutic needs represented the highest percentage of unmet needs in people with Parkinson's disease (85.05%), followed by social/spiritual/emotional needs (82.72%). Physical needs were the lowest reported score (75.01%). Unmet needs were more frequent in those with more severe non-motor symptoms. Also, higher family support, internal locus of control and doctor locus of control were correlated with more unmet needs. CONCLUSION: Understanding factors that determine the type and degree of unmet needs in people with PD is important to provide appropriate nursing care. The findings of this study can be used for providing nursing interventions reflecting unmet needs and reducing their unmet needs to improve the overall well-being of people with PD. IMPACT: This study addressed unmet needs unmet needs specific to Parkinson's disease with respect to their nursing needs. Therapeutic needs were the highest unmet needs in people with PD, followed by social/spiritual/emotional needs, need for certainty and physical needs. The findings may be useful for nurses to identify the unmet needs of people with PD which need to be addressed. By reflecting on unmet needs, nurses can give personally tailored nursing care.

Amyloid-ß-related and unrelated cortical thinning in dementia with Lewy bodies.

Coexisting Alzheimer's disease (AD) pathology is common in patients with dementia with Lewy bodies (DLB). To evaluate the cortical thinning in patients with DLB considering the effect of amyloid-ß (Aß), we compared the regional cortical thickness between control subjects and patients with DLB with abnormal dopamine transporter imaging. Seventeen (43.6%) of 39 patients with DLB and no control subjects had significant Aß deposition on 18F-florbetaben positron emission tomography. Compared to control (n = 15), Aß-negative DLB group (n = 21) had cortical thinning in the bilateral insula, entorhinal, basal frontal, and occipito-parietal cortices. Compared to Aß-negative DLB, Aß-positive DLB group (n = 15) had a lower cortical thickness in the AD-prone brain regions in addition to the bilateral occipital, basal frontal, and somatomotor cortices. After controlling for the amount of Aß deposition, DLB group had cortical thinning in the same regions affected in the Aß-negative DLB group. In summary, patients with DLB had an Aß-independent cortical thinning, while Aß was associated with additional cortical thinning in the AD-prone brain regions and the aggravation of DLB-specific cortical thinning.

The efficacy and limits of magnetic resonance-guided focused ultrasound pallidotomy for Parkinson's disease: a Phase I clinical trial.

OBJECTIVERecently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson's disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia.METHODSA prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson's Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.RESULTSUnilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the "medication-off" UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects.CONCLUSIONSIn the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.Clinical trial registration no.: NCT02003248 (clinicaltrials.gov).

Olfactory dysfunction in Alzheimer's disease- and Lewy body-related cognitive impairment.

INTRODUCTION: Olfactory dysfunction is common in Alzheimer's disease- and Lewy body-related disorders, but its neural correlates have not been clearly elucidated. METHODS: We retrospectively recruited 237 patients with Alzheimer's disease-related cognitive impairment (ADCI) and 217 with Lewy body-related cognitive impairment (LBCI). They were identically evaluated using the Cross-Cultural Smell Identification Test, neuropsychological tests, and brain magnetic resonance imaging. RESULTS: LBCI had more severe olfactory dysfunction than ADCI. Patients with more severe cognitive dysfunction had worse olfactory function in both groups. In ADCI, lower Cross-Cultural Smell Identification Test scores correlated with a lower cortical thickness in brain regions typically affected in Alzheimer's disease, most prominently in the right parahippocampal cortex, whereas in LBCI, the scores correlated with white matter abnormalities in regions vulnerable to Lewy body, including subcortical regions of the orbitofrontal and frontoparietal cortices. DISCUSSION: Our results suggest that cortical atrophy in ADCI and white matter abnormalities in LBCI play important roles in olfactory dysfunction.

The role of 18F-FP-CIT PET in differentiation of progressive supranuclear palsy and frontotemporal dementia in the early stage.

PURPOSE: The purpose of this study was to evaluate whether the pattern of striatal dopamine transporter (DAT) availability could differentiate between progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) in the first few years of the disease. METHODS: We enrolled patients who had Parkinsonism and frontal dysfunction and/or language deficit, visited the clinic within 2 years of the onset of symptoms, and had been followed-up for longer than 5 years; thus resulting in 26 patients with PSP and 24 patients with FTD. By quantitatively analyzing N-(3-[18F]fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane PET, we compared the pattern of DAT availability at the time of the baseline evaluation between the two groups. The discriminatory power of variables including DAT activity and clinical parameters was investigated by receiver operating characteristics (ROC) analyses. Additionally, we analyzed the correlation between striatal subregional DAT availability and cognitive profiles. RESULTS: Patients with PSP and FTD had significantly lower DAT availability than normal controls in the whole striatum and in each striatal subregion. When comparing the two groups, DAT availability was significantly lower in patients with PSP than those with FTD in all striatal subregions. The PSP and FTD groups had generally similar subregional patterns of DAT activity in terms of the anteroposterior and ventrodorsal gradients and asymmetry, except for a different preferential involvement in the caudate. The ROC analysis showed that the DAT activity of the whole striatum had an excellent discriminatory power relative to Parkinsonism or neurocognitive profiles. Correlation analysis showed that verbal memory was significantly correlated with DAT availability in the whole striatum and the putaminal subregion only in patients with PSP. CONCLUSIONS: DAT scans have prognostic value in determining whether patients with Parkinsonism and behavioral and/or language dysfunction will develop features of PSP or FTD later in the disease course.

Parkinson's disease-related non-motor features as risk factors for post-operative delirium in spinal surgery.

BACKGROUND: The clinical features of postoperative delirium are similar to the core features of alpha synuclein-related cognitive disorders, such as Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Therefore, we hypothesized that the non-motor symptoms (NMSs) in Parkinson's disease (PD), which precede the cardinal motor features of PD, are likely to be risk factors for developing postoperative delirium. We investigated the association between PD-related NMSs and postoperative delirium in old people undergoing elective spinal surgery. METHODS: This study was a prospective study. Participants were aged 65 years and older and scheduled to undergo elective spinal surgery. During the enrollment period, 338 individuals were screened, 104 participants were included in the analysis. We assessed eight easily-assessed and representative PD-related NMSs 1 day before the scheduled surgery using tests or questionnaires for each symptom. The presence of delirium was determined by using the short version of the Confusion Assessment Method (CAM). RESULTS: Fifteen (14.4%) of the 104 participants (age, 71.7 ± 4.7 years; men, 34.6%) met the CAM criteria for post-operative delirium. Multivariate logistic analysis showed that decreased olfactory function (odds ratio [OR] 0.63, 95% CI 0.44-0.91) and exhibiting rapid eye movement sleep behavior disorder (RBD, OR 1.45, 95% CI 1.09-1.93) were significantly independent predictors of postoperative delirium. CONCLUSIONS: Our study shows that hyposmia and RBD are significantly independent risk factors for postoperative delirium in general elderly population. Considering that NMSs may represent burden of alpha synuclein deposit, we postulate that an underlying alpha synucleinopathy may correlates with postoperative delirium. SIGNIFICANCE: This study gives a novel insight for the risk factor of postoperative delirium.

Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD. METHODS: Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders. RESULTS: Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score. CONCLUSIONS: The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson's disease.

PURPOSE: Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. METHODS: From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. RESULTS: The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (ß = 16.039, p = 0.033). CONCLUSION: This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.