Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm²) was higher compared to iRBD (0.07 ± 0.07 cm²; p < 0.0001) and controls (0.05 ± 0.03 cm²; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.     

Relationship of substantia nigra hyperechogenicity to risk of Lewy body disease in idiopathic REM sleep behavior disorder patients: a longitudinal study

BackgroundWe examined the relationship between baseline substantia nigra (SN) echogenicity on transcranial sonography (TCS) images and medium-to long-term developments of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) in idiopathic RBD (IRBD) patients.MethodsFrom 2007–2009, TCS and odor identification tests were performed in 34 consecutive IRBD patients (67.9 ± 6.1 years). A medical chart review was conducted in August 2019 to investigate the development of PD or DLB.ResultsOf the 34 IRBD patients, 14 (41.2%) showed SN hyperechogenicity (SN+) on TCS at baseline. There were no significant differences in age, Unified Parkinson's Disease Rating Scale (UPDRS) score, Mini-Mental State Exam (MMSE) score, or odor identification (OSIT-J) score between the SN+ and SN normoechogenicity (SN−) groups at baseline. The phenoconversion rate was 57.4% (n = 8) in the SN+ group (mean 5.8 years from baseline TCS), and 25.0% (n = 5) in the SN− group (mean 8.6 years from baseline TCS). Of those with phenoconversions, there were five PD patients and three DLB patients in the SN+ group, and one PD patient and four DLB patients in the SN− group. The SN+ group had a higher estimated risk for disease development than the SN− group. The coexistence of SN+ with functional anosmia may predict a short-term Lewy body disease onset risk.ConclusionA single baseline TCS for IRBD patients may be a suitable test for screening and predicting groups at high-risk for developing PD or DLB. This may help to select appropriate IRBD patients in clinical trials for disease modifying therapy to prevent progression to PD or DLB.     

Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients.MethodsWe performed TCS in 30 subjects and SPECT with [^99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [^99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared.ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere.ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.     

Transcranial sonography in spinocerebellar ataxia type 2

Objective   To study the use of transcranial brain parenchyma sonography (TCS), in particular the echogenic signal in the substantia nigra (SN), in patients with spinocerebellar ataxia type 2 (SCA2), recently recognized as an uncommon cause of parkinsonism. Methods   Six consecutive and unrelated SCA2 patients without parkinsonian signs, 30 consecutive patients with Parkinson’s disease (PD), and 30 healthy, age- and sexmatched controls were prospectively studied with TCS according to a standardized protocol. Results   Four (67 %) of the six SCA2 patients exhibited SN hyperechogenicity. In two patients, the hyperechogenicity was classified as moderate (unilateral in both) and in two as marked. Differences between the SN echogenicity of the SCA2 group or the PD group and controls were statistically significant (p < 0.001), while there was no difference between the two groups of patients. Conclusions   Transcranial brain parenchyma sonography detects SN hyperechogenicity in the majority of patients with SCA2 without parkinsonian signs. It would be important to reproduce our TCS findings in a larger number of SCA2 patients, as well as to test their possible significance in differentiating SCA2 from other types of SCA.     

Midbrain transcranial sonography in Korean patients with Parkinson's disease.

Transcranial sonography (TCS) is potentially useful for the diagnosis of Parkinson's disease (PD). However, studies on TCS have so far been restricted to European populations. To investigate the efficacy of TCS in Korean PD patients and its correlation with the clinical features, we carried out midbrain TCS in 43 PD patients and 35 normal controls and evaluated the area of the substantia nigra (SN) hyperechogenicity and its ratio to the area of the whole midbrain. In 16 subjects (21%), TCS was unsuccessful due to insufficient acoustic temporal bone windows. The mean area of bilateral SN hyperechogenicity and its ratio to the midbrain area were greater in the PD patients than that in the controls (P < 0.01). In the PD patients, the area of SN hyperechogenicity and its ratio to the individual midbrain area were moderately correlated with the PD duration (r = 0.526 and 0.536, P = 0.01, respectively) but not with the age, UPDRS motor scores or H-Y stage. There was no difference in the SN hyperechogenicity between the tremor-dominant, akinetic-rigid, and mixed-type PD patients. In conclusion, midbrain TCS is an effective diagnostic tool for detecting PD in the Korean population. However, it does not reflect the severity or phenotypes of parkinsonism.     

Orthostatic hypotension predicts motor decline in early Parkinson disease

BackgroundOrthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials.MethodsUsing data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks. We also explored risk factors for worsening orthostatic hypotension over a nearly 2-year period.ResultsAfter controlling for age, disease duration, gender, study drug, change in mini-mental status exam score, levodopa equivalent dose, and baseline UPDRS II or III score respectively, the degree of orthostatic hypotension at enrollment associated with a worsening in UPDRS motor score (t = 2.40, p = 0.017) at week 102 but not with UPDRS ADL score (t = 0.83, p = 0.409). Worsening in orthostatic hypotension during the study associated with longer disease duration (t = 2.37, p = 0.019) and lower body mass index (BMI) (t = −2.96, p = 0.003).ConclusionsBaseline orthostatic hypotension is a predictor of UPDRS motor decline in individuals with early PD and should be accounted for in clinical trial design. Low BMI may predict orthostatic hypotension in PD.     

Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder

Recent studies have reported an increased risk to develop Parkinson's disease (PD) in patients with idiopathic RBD (iRBD). Midbrain hyperechogenicity is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk‐marker in nonparkinsonian subjects. The objective of this study is to assess midbrain echogenicity by TCS in patients with iRBD and compare the findings with the healthy controls. TCS was performed in 55 iRBD patients and in 165 age and sex‐matched controls. The area of echogenicity in the SN region in the iRBD group was significantly increased compared with the control group (P < 0.001). About 19 (37.3%) of patients with iRBD were found to have SN hyperechogenicity when compared with 16 (10.7%) of the controls (P < 0.001). This is the first case‐control study assessing midbrain echogenicity in a large iRBD cohort compared to age‐ and sex‐matched healthy individuals. The finding of an increased prevalence of hyperechogenicity in a subgroup of individuals with a priori increased risk for PD supports the potential role of hyperechogenicity as a risk marker for PD. The prospective follow‐up of this iRBD cohort is needed to establish if those with midbrain hyperechogenicity will go on to develop clinically defined PD or not. © 2009 Movement Disorder Society     

Transcranial ultrasound in different monogenetic subtypes of Parkinson's disease

Abstract Hyperechogenicity of the substantia nigra (SN) has been found to be a typical sign in idiopathic Parkinson's disease (PD), prevalent in more than 90% of affected individuals. To see whether SN hyperechogenicity is also characteristic for monogenetically caused PD, we investigated PD patients with alpha-synuclein, LRRK2, parkin, PINK1 and DJ-1 mutations by transcranial sonography (TCS). In all these patients the area of SN echogenicity was significantly larger than in healthy controls, but smaller, than in idiopathic PD. As SN hyperechogenicity could be related to an increased iron content of the SN, these findings suggest that iron may play a less significant role in the pathogenesis of monogenetically caused compared to idiopathic PD.     

Effect of olfactory impairment and white matter hyperintensities on cognition in Parkinson's disease

IntroductionAlthough white matter hyperintensities (WMH) and olfactory dysfunction are independently associated with the cognitive impairments in Parkinson's disease (PD), the effects of simultaneous presence of these abnormalities remain unknown. Thus, we investigated the different effects of deep WMH and periventricular WMH on olfactory and cognitive performance and evaluated the additive effects of the concurrent presence of WMH and olfactory dysfunction on cognitive performance in PD.MethodsWe enrolled 171 patients with non-demented PD whose WMH scores were assessed using a semi-quantitative visual rating system. The olfactory and cognitive performance was assessed using the Cross-Cultural Smell Identification (CCSI) test and the Seoul Neuropsychological Screening Battery. Additionally, the additive effects of concurrent WMH and olfactory dysfunction on cognitive performance were investigated using binary logistic regression.ResultsThe deep WMH score exhibited a significant negative correlation with the CCSI score (p = 0.026) but the total WMH and periventricular WMH did not. A multiple regression analysis revealed that the total WMH (β = −0.109, p = 0.011) and deep WMH (β = −0.153, p = 0.020) severities had significant negative correlations with semantic fluency. A logistic regression analysis revealed that the simultaneous presence of severe olfactory dysfunction and deep WMH was associated with a greater risk for the semantic fluency impairments (odds ratio = 15.909, p = 0.0005) compared to patients with mild deep WMH or high CCSI scores.ConclusionsThese data indicate that deep WMH was closely coupled with olfactory impairments and cognitive decline in PD. Moreover, the concurrent presence of severe deep WMH and olfactory impairments has a greater influence on semantic fluency.     

Substantia nigra echogenicity is normal in non-extrapyramidal cerebral disorders but increased in Parkinson's disease

Summary. Transcranial sonography (TCS) revealed substantia nigra (SN) hyperechogenicity in idiopathic Parkinson's disease (IPD). To further evaluate specificity of this finding, we examined 30 IPD patients and 30 age-matched subjects with non-extrapyramidal cerebral disorders (NED). All IPD patients showed a SN hyperechogenicity, in 17 it was bilateral and in 13 unilateral. 7 NED patients had a SN hyperechogenicity, in all it was unilateral, confirming previous results in healthy subjects. Bilateral SN hyperechogenicity indicates IPD and normal SN echogenicity indicates NED. In 30% of patients TCS does not distinguish between IPD and NED. Data further support the assumption that bilateral SN hyperechogenicity is specific for IPD. Received April 30, 2001; accepted October 17, 2001     

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD–related RLS (pRLS). Sixty‐three PD patients (median age 64.6 ± 10.6 years), 40 iRLS patients (53.1 ± 11.7 years), and 40 healthy controls (69.1 ± 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD‐RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD‐RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. © 2010 Movement Disorder Society     

Microglia activation is related to substantia nigra echogenicity

Hyperechogenicity of the substantia nigra (SN) is a sensitive marker for Parkinson’s disease (PD). Previously, a relation between SN echogenicity and iron as well as neuromelanin content could be described in 60 human brains. In the present study on a subset of 33 brains, SN echogenicity was found to be correlated with microglia activation (ρ = 0.46, p = 0.008) after correction for iron and neuromelanin content. These findings strengthen the hypothesis of a close pathophysiological connection between SN hyperechogenicity and PD pathology.     

Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson's disease

ObjectiveMotor asymmetry in Parkinson's disease (PD) is evident clinically and on functional neuroimaging, but not reported in diffusion tensor imaging (DTI). We aim to determine if asymmetry in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) can be detected in the substantia nigra (SN) of PD subjects.MethodsDTI scans were performed on 11 PD and 12 healthy subjects. Regions of interest (ROIs) were drawn by 2 independent raters at the caudal, middle and rostral SN on each side. FA and ADC were extracted from the ROIs.ResultsSignificant asymmetry was observed in the FA (p < 0.005) and ADC (p < 0.00005) at the rostral SN of PD subjects. The differences in FA and ADC across the left and right rostral SN were significantly different between PD and healthy subjects, p < 0.05 and p < 0.02 respectively. PD subjects had significantly higher ADC at the left rostral SN than healthy subjects (p < 0.01). Significant correlation between the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and the FA was noted in the left rostral SN (r = 0.7, p < 0.03).ConclusionsAsymmetry in DTI indices was noted at the rostral SN of PD subjects. The relationship between FA in the SN and UPDRS motor score was studied. Our findings may provide a model for better understanding of the implication of FA reduction in the SN.     

Association between common genetic risk variants and depression in Parkinson's disease: A dPD study in Chinese

IntroductionPrediction of depression in patients with Parkinson's disease (PD) remains challenging. We investigated whether the common susceptible genetic variants for PD are associated with the risk and improves prediction of development of depression in PD (dPD).Methods1134 individuals with a primary diagnosis of PD were recruited. Demographic information, Unified Parkinson's Disease Rating Scale (UPDRS), and 17-item Hamilton Rating Scale for Depression (HAMD) were obtained. Nine variants located in six susceptible genes for PD were determined in all subjects. Logistic regression analyses were used to identify the study genetic variants that individually and collectively best predicted the presence of depressive disorder (HAMD ≥14).ResultsDepression occurred in 19.8% of patients with PD. The GBA L444P variant was associated with an increased risk of depression (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.31–5.53, P = 0.007) and SNCA-Rep1 (CA)12/12 showed a decreased risk for the presence of depression (OR = 0.54, 95% CI = 0.29–0.99, P = 0.049) in the PD population after adjusted for demographic and clinical factors. Stepwise logistic regression model found that female sex, UPDRS part II score, motor fluctuation, GBA L1444P and SNCA Rep-1 variants collectively best predict depression in PD.ConclusionsBesides non PD-specific and PD-specific clinical correlates, we showed that GBA L444P and SNCA Rep-1 were also associated with dPD. Our findings highlight the crucial role of genetic variants for the prediction of dPD in clinical practice and may shed light on the future development of better therapeutic targets for dPD.     

Transcranial sonography in patients with Parkinson's disease with glucocerebrosidase mutations

ObjectivesThe aim of this study was to search for possible differences in the findings of transcranial sonography (TCS) between groups of patients with glucocerebrosidase (GBA)-associated Parkinson's disease (PD) (4 patients with Gaucher disease type 1 and parkinsonism [GD+PD+] and 18 PD patients with heterozygous GBA mutations; [GBA+PD+]) and groups of 12 patients with Gaucher disease type 1 and no signs of parkinsonism (GD+PD?), 9 asymptomatic carriers of heterozygous GBA mutations (GBA+PD?), 32 sporadic PD patients (sPD), and 43 healthy controls.ResultsIn all groups of patients, except asymptomatic carriers of heterozygous GBA mutations (mean ± SD: 0.16 ± 0.03 cm²), the maximal areas of substantia nigra hyperechogenicity (aSN-max) was higher (GD+PD+: 0.28 ± 0.15 cm²; GD+PD?: 0.18 ± 0.06 cm²; GBA+PD+: 0.27 ± 0.06 cm²; sPD: 0.28 ± 0.10 cm²) when compared to controls (0.12 ± 0.08 cm²) (p = 0.001). In GBA-associated PD (GD+PD+ and GBA+PD+) and sPD, aSNmax values were very similar. Moderate or marked SN hyperechogenicity was present in 87.5% of sPD patients and in 83% of PD patients with heterozygous GBA mutations, but in only 11.6% of controls, and in 22.2% and 33.3% of patients from GBA+PD? and GD+PD? groups, respectively (p < 0.001). The prevalence of interrupted or missing echogenicity of the brainstem raphe differed between the groups (p = 0.046), while no difference was observed in the diameter of the third ventricle.ConclusionsTCS findings in GBA-associated PD were consistent to those of patients with sporadic PD.     

Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized,double-blind,placebo-controlled,phase II/III study

IntroductionSafinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off.MethodsThis 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index.ResultsA total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p < 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%).ConclusionAs an adjunct to l-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.     

Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly

Enlarged substantia nigra hyperechogenicity (SN+) assessed by transcranial sonography (TCS) may be associated with Parkinson's disease (PD) risk markers such as impaired motor performance and hyposmia. The aim of this multicenter cross‐sectional study was to define the association between SN+ and these risk markers in a large population older than 50 years without the diagnosis of PD. In three centers (Tuebingen, Homburg, and Innsbruck), 1,839 individuals were examined. The echostatus of the SN was assessed by TCS, motor performance by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and olfactory function with Sniffin' Sticks. From the 1,603 subjects included in the analysis, 16.2% were SN+, 23.0% scored above zero in the UPDRS motor section, and 28.0% were hyposmic as defined by less than 75% correctly classified Sniffin' Sticks. SN+ was associated with a UPDRS motor score above zero (OR 1.45, 95% CI 1.08–1.96) and with a lower odor identification capability (OR 1.48, 95% CI 1.12–1.96). The combination of these two features (OR 1.98, 95% CI 1.25–3.15) and UPDRS motor scores ≥3 lead to higher OR. It is concluded that SN+, impaired motor performance, and hyposmia are frequently observed in the elderly and in isolation are unspecific and of limited use to predict a subject's risk for PD. Whether the association of SN+ with both impaired motor performance and hyposmia as seen in this study predicts an increased risk for the development of PD needs to be evaluated in the follow‐up investigations. © 2010 Movement Disorder Society     

Different iron deposition patterns in early- and middle-late-onset Parkinson's disease

BackgroundIron deposition may contribute to the clinical symptoms in Parkinson's disease (PD). With partial different clinical manifestations, the iron deposition patterns between patients with early-onset Parkinson's disease (EOPD) and middle-late-onset Parkinson's disease (M-LOPD) are still unclear. This study was designed to investigate the patterns of iron deposition and their clinical relevance in EOPD and M-LOPD patients, using quantitative susceptibility mapping technique.Materials and methodsThirty-five EOPD patients and 24 matched young controls, 33 M-LOPD patients and 22 matched older controls were recruited in the study. The iron content in the deep grey matter nuclei in the basal ganglia and midbrain were measured, and compared between patients and their corresponding controls. The correlations of regional iron content and clinical features were explored in patient groups.ResultsBoth M-LOPD and EOPD patients showed increased iron content in the substantia nigra (SN) pars compacta and SN pars reticulata. Increased iron content in the putamen was only observed in M-LOPD patients. The relationship between the increased iron content and disease severity (H&Y stages, UPDRS II scores and UPDRS III scores) was observed in M-LOPD patients, but not in EOPD patients.ConclusionOur study suggested that the iron deposition pattern was greatly influenced by the age of PD onset, which increases our understanding of the different pathological underpinnings of EOPD and M-LOPD patients.     

Dopamine reuptake transporter–single‐photon emission computed tomography and transcranial sonography as imaging markers of prediagnostic Parkinson's disease

Objective: The objective of this study was to examine whether prediagnostic features of Parkinson's disease (PD) were associated with changes in dopamine reuptake transporter–single‐photon emission computed tomography and transcranial sonography. Methods: Prediagnostic features of PD (risk estimates, University of Pennsylvania Smell Identification Test, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire, and finger‐tapping scores) were assessed in a large cohort of older U.K. residents. A total of 46 participants were included in analyses of prediagnostic features and MDS‐UPDRS scores with the striatal binding ratio on dopamine reuptake transporter–single‐photon emission computed tomography and nigral hyperechogenicity on transcranial sonography. Results: The striatal binding ratio was associated with PD risk estimates (P = .040), University of Pennsylvania Smell Identification Test (P = .002), Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire scores (P = .024), tapping speed (P = .024), and MDS‐UPDRS motor scores (P = .009). Remotely collected assessments explained 26% of variation in the striatal binding ratio. The inclusion of MDS‐UPDRS motor scores did not explain additional variance. The size of the nigral echogenic area on transcranial sonography was associated with risk estimates (P < .001) and MDS‐UPDRS scores (P = .03) only. Conclusions: The dopamine reuptake transporter–single‐photon emission computed tomography results correlated with motor and nonmotor features of prediagnostic PD, supporting its potential use as a marker in the prodromal phase of PD. Transcranial sonography results also correlated with risk scores and motor signs. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50–70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN− and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10–12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.