Structural and functional brain alterations in patients with idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: To investigate structural and functional alterations in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with healthy controls. METHODS: Twenty-seven patients with polysomnography-confirmed iRBD and 33 healthy subjects were recruited. All subjects underwent a 3-tesla structural and resting-state functional magnetic resonance imaging (fMRI) examination. Voxel-based morphometry (VBM) analysis was performed to assess grey matter alterations between groups. The amplitude of low-frequency fluctuations (ALFF) was calculated and then compared to measure differences in spontaneous brain activity. Correlations were performed to explore associations between imaging metrics and clinical characteristics in iRBD patients. RESULTS: Compared with healthy controls, patients with iRBD had decreased grey matter volume in the frontal, temporal, parietal, occipital cortices as well as increased grey matter volume in cerebellum posterior lobe, putamen, and thalamus. Patients with iRBD also exhibited increased ALFF values in the right parahippocampal gyrus. Olfaction correlated with ALFF value changes in occipital cortices. CONCLUSIONS: Patients with iRBD had widespread decreases of grey matter volume. Increases of grey matter volume in cerebellum, putamen, and thalamus may suggest a compensatory effect, while the altered ALFF values in parahippocampal gyrus and occipital cortices may play a role in the underlying process of neurodegeneration in this disorder.

Decreased Penetrance of Parkinson's Disease in Elderly Carriers of Glucocerebrosidase Gene L444P/R Mutations: A Community-Based 10-Year Longitudinal Study.

BACKGROUND: Heterozygous mutations in the glucocerebrosidase gene (GBA) have been shown to be an important genetic risk factor for Parkinson's disease (PD) worldwide. However, the penetrance of GBA heterozygote for L444P, the common mutation for Asian population, is not known in older Chinese people. OBJECTIVES: To assess the conversion rate to PD in identified carriers of GBA L444P/R mutations in Chinese community-dwelling older adults. METHODS: The GBA gene was sequenced for mutations at position 444 in 8405 people older than 55 years who participated in the Beijing Longitudinal Study on Aging II cohort. Nine subjects were identified as heterozygous carriers of GBA L444P or L444R mutations at baseline and clinically followed up from 2009 to 2019 to investigate their PD conversion, motor and nonmotor symptoms, and change of vesicular monoamine transporter type 2 using tracer of [18 F]9-fluoropropyl-(+)-dihydrotetrabenazine (18 F-DTBZ, also known as 18 F-AV-133). RESULTS: Eight heterozygous GBA L444P and 1 L444R mutation carriers were identified without PD at baseline, and none of them developed clinical parkinsonism after a 10-year follow-up. CONCLUSIONS: Although GBA mutations may lead to an earlier onset PD, the majority of GBA L444P heterozygotes in older adults may not convert to PD. Further studies are warranted to identify factors that modify the risk of conversion. © 2020 International Parkinson and Movement Disorder Society.

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BACKGROUND: Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized. OBJECTIVES: To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization. METHODS: We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration. RESULTS: CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68). CONCLUSIONS: CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.

Clinical Manifestation of Parkinson's Disease in Association with Rapid Eye Movement Sleep Behavior Disorder Onset.

AIMS: To confirm whether the presence and/or timing of rapid eye movement sleep behavior disorder (RBD) onset were associated with differences in clinical features of Parkinson's disease (PD), clinical characteristics of PD patients with RBD occurring before and after PD diagnosis were investigated. METHODS: Consecutive PD patients were enrolled between July 2011 and February 2012. RBD questionnaire Hong Kong and clinical interviews were used to identify RBD symptoms and onsets. All patients underwent evaluations to collect clinical and treatment information. RESULTS: Of all 79 PD patients, 21 (26.6%) and 22 (27.8%) patients had RBD prior to (RBD-PD) and after PD diagnosis (PD-RBD), respectively. Thirty-six (45.6%) PD patients reported no RBD at the time of study (PD-NRBD). PD-RBD had similar clinical features as PD-NRBD did except that Epworth sleepiness scale score was significantly higher in PD-RBD (p = 0.04). Compared to PD-RBD and PD-NRBD, RBD-PD had a higher frequency of reporting excessive daytime sleepiness (p = 0.019, p = 0.008, respectively) and constipation (p = 0.046, p = 0.032, respectively). CONCLUSION: Our preliminary results suggest that RBD-PD might be clinically different from PD-RBD, which appears to share similar characteristics with PD-NRBD, regarding only non-motor functions.

Non-motor symptoms in Chinese Parkinson's disease patients with and without LRRK2 G2385R and R1628P variants.

Non-motor symptoms (NMS) are common among patients with Parkinson's disease (PD). However, reports on NMS in Chinese PD population are scarce. Little is known about NMS in patients with Asian specific leucine-rich repeat kinase 2 (LRRK2) variants in G2385R and R1628P. This study aimed to elucidate the clinical characteristics of NMS in Chinese PD patients and to ascertain if there were differences in NMS between PD patients with and without LRRK2 variants. A multicenter, observational study was conducted with 1,225 sporadic PD (sPD) patients recruited from a PD cohort of the Chinese National Consortium on neurodegenerative diseases, 163 participants had the LRRK2 variants. The Non-motor Symptom Questionnaire (NMSQ) was used to screen for the presence of NMS. This study found the majority of sPD patients (97.6 %) had at least one NMS. A mean of 8.72 NMS (SD = 5.43) was reported per patient. Forgetfulness, constipation and daytime sleepiness were found to be the most frequent NMS. Moreover, the number of NMS was positively correlated with the age, disease duration, Hoehn & Yahr stage and the motor scores of the unified Parkinson's disease rating scale. Although no discrepancy was found in the number of NMS between sPD patients with and without LRRK2 variants, nocturia was less common in LRRK2 variants carriers than in non-carriers (P = 0.045). NMS appear to be prevalent in Chinese sPD population. There are no differences in the NMS phenotype between LRRK2 and no LRRK2 patients.

[Polymorphisms of catechol-O-methyltransferase and monoamine oxidase B genes among Chinese patients with Parkinson's disease].

OBJECTIVE: To study polymorphisms of catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B) genes among Chinese patients with Parkinson's disease. METHODS: Genotypes of the COMT and MAO-B genes of 1408 patients with Parkinson's disease was sequenced using Sanger method. And these patients were recruited by Chinese Parkinson Study Group from 29 research centers throughout the country. RESULTS: The genotypic frequencies of COMT rs4680 AA, AG, GG were 8.9%, 42.0% and 49.1%. Those of rs4818 CC, CG, GG were 42.5%, 45.6% and 11.9%, respectively. The genotype frequencies of MAO-B rs1799836 A/AA, AG, G/GG were 74.4%, 14.1% and 11.5%, respectively. The haplotype formed by COMT rs4680 (GG) and MAO-B rs1799836 (A/AA) genotype has a frequency of 36.86%. CONCLUSION: Polymorphisms of COMT and MAO-B genes has a unique characteristics among Chinese patients with Parkinson's disease. They may be related with differences in drug response in such patients.

Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson's disease.

The affect of gender differences on clinical presentation of Parkinson's disease (PD) remains controversial. De novo PD subjects were recruited from a trial-based multicenter cohort in clinical sites of Chinese Parkinson Study Group. Demographic information, motor and non-motor symptom measurements were performed by face-to-face interview using specific scales. Scores and frequencies of symptoms were compared between male and female patients, and regression models were used to control the effects of age and disease duration. Totally 428 PD patients were enrolled in this study, and 60.3 % of them were male. Total UPDRS scores were not significantly different between male and female (25.02 ± 12.84 vs. 25.24 ± 13.22, adjusted p = 0.984). No significant gender differences were found on scores for four cardinal motor signs, neither on motor subtypes (PIGD 19.0 vs. 15.9 %, adjusted p = 0.303). Female patients more likely had depressive symptoms (38.8 vs. 27.5 %, adjusted p = 0.023; CES-D score 13.78 ± 10.91 vs. 11.23 ± 9.42, adjusted p = 0.015). Male patients had significantly higher scores for MMSE (28.26 ± 2.21 vs. 27.00 ± 3.38, adjusted p = 0.0001), and lower scores for identification (1.39 ± 1.63 vs. 2.01 ± 2.63, adjusted p = 0.002) in ADAS-cog. No significant differences were found for other non-motor symptoms including motivation problems (male 29.8 % vs. female 30.6 %, adjusted p = 0.760), fatigue (62.6 vs. 70.5 %, adjusted p = 0.140), constipation (37.2 vs. 30.1 %, adjusted p = 0.243), and sleep quality (57.6 vs. 61.3 %, adjusted p = 0.357; PSQI score: 5.62 ± 3.31 vs. 6.10 ± 3.53, adjusted p = 0.133). Female might be more depressed and have worse performance on cognition in early untreated PD patients, but gender differences are not apparent on motor and other non-motor symptoms.

Non-motor symptoms in treated and untreated Chinese patients with early Parkinson's disease.

Non-motor symptoms (NMS) are important preclinical features of Parkinson's disease (PD) and have become the leading cause of poor quality of life with disease progression. There are little data on how antiparkinsonian medications influence the NMS in PD at early stage. In this study, we explored the distribution of NMS in treated and untreated PD and investigated the association between NMS and antiparkinsonian medications in Chinese patients with early PD. Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical trials. Face-to-face interviews and evaluations were performed for clinical information. NMS were compared in patients with or without antiparkinsonian treatment, and between subgroups of dopaminergic medications. Eight hundred and sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were free of NMS. PD patients with antiparkinsonian medications had a significantly higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn & Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis revealed that Levodopa Equivalent Dose (LED) was associated with constipation (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in the prodromal stage of PD, antiparkinsonian treatment is associated with increased frequency of some NMS, which may challenge the management for PD.

Validation of the Beijing version of the REM sleep behavior disorder questionnaire (RBDQ-Beijing) in a mainland Chinese cohort.

REM sleep behavior disorder (RBD) is one type of parasomnia characterized by nocturnal complex motor activity associated with dream mentation. Growing evidence has indicated that RBD is a preclinical stage of neurodegenerative diseases. Therefore screening RBD patient is becoming important. The RBD Questionnaire-Hong Kong (RBDQ-HK) is an effective questionnaire to screen RBD patients. However, it is hard to distinguish RBD with the questionnaire from severe OSAS patients, who could mimic some symptoms of RBD patients. Therefore, we made RBDQ-Beijing by adding two screening questions for OSAS into original RBDQ-HK, including habitual loud snoring and witnessed apnea during sleep. To validate and compare these two questionnaires, 224 subjects were enrolled and screened with these questionnaires, and consequently analyzed with video-polysomnography. Receiver-operator characteristics curve analysis was conducted to attain the best cut-off values of the RBDQ-HK and RBDQ-Beijing. For the RBDQ-HK, the sensitivity was 97.1% and the specificity was 83.2%. More than half of misclassified RBD patients were proved to be severe OSAS patients. For the RBDQ-Beijing, the sensitivity was 95.8% and specificity was 94.3%, indicating that our questionnaire is able to distinguish RBD from severe OSAS patients. In conclusion, RBDQ-Beijing is of help to improve the specificity in RBD screening without excluding the patients with RBD combined OSAS. Therefore the RBDQ-Beijing may be a better screening and preliminary diagnostic tool for RBD than the RBDQ-HK. Moreover, the RBDQ-Beijing would be important for early diagnosis of neurodegenerative diseases and for prevention of injuries to the patient or the patient's bed partner.

Gait Analysis with Wearable Sensors in Isolated REM Sleep Behavior Disorder Associated with Phenoconversion: An Explorative Study.

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Association between postural tremor and risk of disability in community-dwelling older people.

BACKGROUND: The prevalence of postural tremor increases with age and the tremor has been found to be associated with aging-related physiological decline. However, whether postural tremor in older adults is associated with adverse outcomes such as disability is unclear. This study investigated the association between postural tremor and the risk of disability in activities of daily living (ADL) among community-dwelling older people. METHODS: Data were derived from a population-based study of Chinese adults aged ≥55 years. Postural tremor was assessed at baseline using a two-step method (i.e., tremor screening followed by examination of positive cases). ADL disability was determined using an 8-item questionnaire, which covered the mobility and self-care domains of ADL. Participants free of ADL disability at baseline were followed for up to 4 years. RESULTS: The prospective analyses included 5868 participants. Participants with postural tremor were at greater risk of incident ADL disability, particularly disability in the mobility domain of ADL. After multivariate adjustment, postural tremor was not significantly associated with incident ADL disability (multivariate-adjusted relative risk [RR] = 1.05, 95% confidence interval [CI] = 0.77-1.43), and was marginally associated with incident disability in the mobility domain of ADL (multivariate-adjusted RR = 1.36, 95% CI = 0.98-1.88). The risk of mobility-related ADL disability was significantly increased among men, but not women, with postural tremor (multivariate-adjusted RR = 1.84, 95% CI = 1.11-3.05). Older age and an increased number of chronic comorbidities mainly explained the higher risk of ADL disability in older people with postural tremor. CONCLUSIONS: Postural tremor in older adults is associated with greater incidence of ADL disability, particularly mobility-related ADL disability. The association is largely due to older age and a higher prevalence of chronic comorbidities in older people with postural tremor. Postural tremor is not a strong independent predictor of ADL disability in older people.

Musculoskeletal Pain in Parkinson's Disease.

BACKGROUND: Musculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain. OBJECTIVES: To investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD. METHODS: We enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain. RESULTS: Two hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07-2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63-6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life. CONCLUSIONS: The lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Detection of Motor Dysfunction With Wearable Sensors in Patients With Idiopathic Rapid Eye Movement Disorder.

Patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for conversion to synucleinopathy and Parkinson disease (PD). This can potentially be monitored by measuring gait characteristics of iRBD patients, although quantitative data are scarce and previous studies have reported inconsistent findings. This study investigated subclinical gait changes in polysomnography-proven iRBD patients compared to healthy controls (HCs) during 3 different walking conditions using wearable motor sensors in order to determine whether gait changes can be detected in iRBD patients that could reflect early symptoms of movement disorder. A total 31 iRBD patients and 20 HCs were asked to walk in a 10-m corridor at their usual pace, their fastest pace, and a normal pace while performing an arithmetic operation (dual-task condition) for 1 min each while using a wearable gait analysis system. General gait measurements including stride length, stride velocity, stride time, gait length asymmetry, and gait variability did not differ between iRBD patients and HCs; however, the patients showed decreases in range of motion (P = 0.004) and peak angular velocity of the trunk (P = 0.001) that were significant in all 3 walking conditions. iRBD patients also had a longer step time before turning compared to HCs (P = 0.035), and the difference between groups remained significant after adjusting for age, sex, and height. The decreased trunk motion while walking and increased step time before turning observed in iRBD may be early manifestations of body rigidity and freezing of gait and are possible prodromal symptoms of PD.

Validation of a new olfactory test for Chinese Parkinson's disease patients.

INTRODUCTION: Hyposmia is a common non-motor symptom in Parkinson's disease (PD) and has been used to assist PD diagnosis and early screening of prodromal patients. Although the Brief Smell Identification Test (B-SIT) is the most commonly used olfactory test, its utility was limited by the culture difference in recognition of the smells included in the test. We have developed a new modified B-SIT test for Chinese (B-SITC), and validated and compare it with B-SIT in Chinese PD patients. METHODS: From 2015 to 2018, PD patients were recruited from the Movement Disorder Clinic of Xuanwu Hospital and healthy controls were recruited from the Beijing Longitudinal Study on Aging Cohort II. The two olfactory tests were used in healthy volunteers and PD patients. RESULTS: A total of 428 subjects participated in the study: 211 healthy controls and 217 PD patients. The average B-SIT and B-SITC scores were significantly different between control and PD groups (B-SIT, 9.18 ± 1.94 vs. 6.90 ± 2.44, P = 0.0001; B-SITC, 8.60 ± 1.93 vs. 5.91 ± 2.21, P = 0.0001). The B-SITC had good sensitivity (73.1%), specificity (76.8%), positive predictive value (76.8%), and negative predictive value (73.1%) for the diagnosis of Chinese PD, and the area under the curve (AUC) value was greater for the B-SITC than for the B-SIT (0.838 vs. 0.761). CONCLUSIONS: The B-SITC is useful for the clinical assessment of olfactory function in Chinese PD patients.

Risk factors for possible REM sleep behavior disorders: A community-based study in Beijing.

OBJECTIVE: To explore the risk factors for idiopathic REM sleep behavior disorder (RBD) in a community population in Beijing. METHODS: Participants aged 55 years and above were recruited from the Beijing Longitudinal Study on Aging II cohort. We identified individuals with possible RBD (pRBD) using the validated RBD Questionnaire-Hong Kong in 2010. A series of environmental, lifestyle, and other potential risk factors were assessed via standardized questionnaires in 2009. Multivariable logistic regression analysis was performed to investigate the association between the studied factors and pRBD. RESULTS: Of 7,225 participants who were free of parkinsonism and dementia, 219 (3.0%) individuals were considered as having pRBD. Participants with pRBD reported more nonmotor and motor symptoms of Parkinson disease (PD) with adjusted odds ratios (ORs) ranging from 1.10 to 4.40. Participants with pRBD were more likely to report a family history of parkinsonism or dementia (OR 3.03, 95% confidence interval [CI] 1.23-7.46). There was a significant association between pRBD and self-reported hyperlipidemia (OR 1.51, 95% CI 1.09-2.10), ever smoking (OR 1.79, 95% CI 1.20-2.65), prior carbon monoxide (CO) poisoning (OR 2.30, 95% CI 1.39-3.83), and nonoccupational exposure to pesticides (OR 2.21, 95% CI 1.40-3.50). CONCLUSION: Our study replicated previously reported associations between pRBD and hyperlipidemia, smoking, pesticide exposure, and several prodromal PD symptoms. We also found previously unreported links with a positive family history of parkinsonism or dementia and CO poisoning. Risk factor profiles for pRBD partially resemble those defined for PD, but also differ in distinct ways.

Education Moderates the Association of Probable REM Sleep Behavior Disorder With Cognitive and Motor Impairments in Community-Dwelling Older People.

Objectives: To investigate the relationship between probable rapid eye movement (REM) sleep behavior disorder (pRBD) and cognitive/motor impairments in a community-dwelling population and explore the moderating effects of education. Methods: In this cross-sectional study of the Beijing Longitudinal Study of Aging II (BLSA II), 4,477 subjects (≥55 years) fulfilled the inclusion criteria. pRBD was determined by the RBD Questionnaire-Hong Kong (RBDQ-HK). Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to test the global cognitive performance. Walking speed was used to measure motor function. Logistic regression was performed to assess the relationship between pRBD and cognitive/motor impairments and the moderating effects of education. Results: There were 147 participants (3.3%) with pRBD. Participants with pRBD showed increased risks for cognitive impairment [odds ratio (OR) = 1.88, 95% CI 1.24-2.85, p = 0.003], decreased gait speed (OR = 1.43, 95% CI 1.02-2.01, p = 0.03), but not for mild cognitive impairment (MCI) (measured by MoCA: OR = 1.01, 95% CI 0.68-1.50, p = 0.95; measured by MMSE: OR = 0.90, 95% CI 0.59-1.37, p = 0.62). Education modified the effect of pRBD on MCI (measured by MoCA: p < 0.001; measured by MMSE: p = 0.061) and gait speed (p = 0.008). Conclusions: Our findings suggest that pRBD increases the risk of cognitive/motor impairments for a community-dwelling older population, and education could alleviate the negative effects. These findings implicate that education may have beneficial effects on delaying the onset of cognitive/motor decline in pRBD subjects.

Postural Tremor Is Associated with Gait and Balance Impairments in Community-Dwelling Older People.

OBJECTIVES: We sought to assess associations of postural tremor with gait and balance impairments among community-dwelling older people in both cross-sectional and longitudinal analyses. DESIGN: A prospective cohort study. SETTING: Communities in Beijing, China. PARTICIPANTS: This study included 7075 individuals aged 55 years or older. MEASUREMENTS: Postural tremor was assessed using a two-step method (tremor screening followed by a confirmation examination of positive cases) at baseline. Gait and balance performances were measured with the Tinetti Mobility Test at baseline and 1 year later. RESULTS: At baseline, 45 (24.7%) of 182 tremor cases vs 663 (9.6%) of 6893 controls had gait and balance impairments. At 1-year follow-up, 19 (21.1%) of 90 tremor cases vs 416 (9.8%) of 4262 controls experienced a rapid decline in gait and balance performance. After controlling for potential confounders, postural tremor was associated with gait and balance impairments at baseline (odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.20-2.62; p = .004) and a rapid decline in gait and balance performance at 1-year follow-up (OR = 1.99; 95% CI = 1.17-3.39; p = .01). CONCLUSION: In this population-based cohort study, we found postural tremor was associated with gait and balance impairments among community-dwelling older people in both cross-sectional and longitudinal analyses. Our findings suggest that motor function should be routinely evaluated and monitored in older people with postural tremor. J Am Geriatr Soc 67:799-803, 2019.

Validation of the utility of the Brief Smell Identification Test in Chinese patients with Parkinson's disease.

INTRODUCTION: Hyposmia is a common non-motor symptom occurring in Parkinson's disease (PD), and has been included in the diagnostic criteria. Although a version of the Brief Smell Identification Test (B-SIT) has been developed specifically for Chinese populations, there have been no reports of the utility of this test in the diagnosis of PD in China. OBJECTIVE: Considering the influence of cultural factors on olfactory test findings, we sought to investigate the utility and efficiency of the B-SIT in Chinese PD patients. METHODS: PD patients were recruited from the Movement Disorder Clinic of Xuanwu Hospital, and healthy controls were recruited from the Beijing Longitudinal Study on Aging Cohort II, between 2015 and 2016. The B-SIT was used for olfactory function testing in all subjects, and the familiarity of 59 odors questionnaire was performed for the investigation of familiarity of odors. RESULTS: A sample of 275 subjects participated in the study, including 112 healthy controls and 163 PD patients. The sensitivity (64.1%), specificity (83.9%), positive predictive value (83.5%) and negative predictive value (64.8%) for identifying PD were measured with the B-SIT. The consistency values between the results of self-reported smell loss and hyposmia identified by B-SIT in control and PD groups were 74.8% and 64.2%, respectively. Most of the odors in the B-SIT were familiar to people in the Chinese population, based on a survey of 3356 subjects using a familiarity questionnaire. CONCLUSIONS: It is recommended to use the B-SIT olfactory test instead of self-reported smell loss for PD diagnosis for Chinese.

Visual dysfunction in patients with idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: Visual dysfunction is a common feature in α-synucleiopathies but rarely assessed in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The current study is set to investigate the comprehensive visual function in iRBD as compared to patients of Parkinson's disease (PD) with RBD. METHODS: Eighty-three iRBD subjects diagnosed with polysomnograph (PSG), 52 early PD patients (Hoehn-Yahr stages<3) with RBD symptom prior to onset of motor symptoms and 79 healthy controls without RBD diagnosed based on RBD Questionnaire-Hong Kong (RBDQ-HK) were enrolled in this study. Visual function including color discrimination, stereopsis function, visual illusion (VI) or hallucination (VH) were assessed in addition to UPDRS, Purdue Pegboard test (PPT) and cognitive tests. RESULTS: Abnormal color discrimination and stereopsis were presented significantly higher in both iRBD and PD patients as compared to controls and more severe in PD than in iRBD. Color discrimination was decreased in all four color in PD patients but not green color in iRBD subjects. Stereopsis test was abnormal in both iRBD and PD, but the proportion of subjects with abnormal stereopsis was significantly higher in PD patients (69.6% vs 42%). Similar number of subjects with iRBD and PD were presented with illusion but only PD patients reported more hallucination. Changes of visual function were associated with age and cognition in both iRBD and PD subjects but was also affected independently by disease duration and clinical stage or fine motor function in PD. In addition, decreased fine motor function demonstrated by PPT was also observed in some iRBD subjects. CONCLUSION: Our results demonstrated comprehensively that visual dysfunction was present in iRBD subjects similar but in a less degree of severity to PD patients, and associated with age, cognition and motor deficit. Whether or not it can be useful in predicting iRBD conversion to PD warrants further investigation.

Prevalence of pre-diagnostic symptoms did not differ between LRRK2-related, GBA-related and idiopathic patients with Parkinson's disease.

INTRODUCTION: Glucocerebrosidase (GBA) mutations and leucine-rich repeat kinase 2 (LRRK2) variants are the most common genetic risk factors for late-onset Parkinson's disease (PD). In this study, we aimed to investigate the differences in pre-diagnostic symptoms of PD associated with the variants. METHODS: The participants were recruited from 24 centers across China and genotyped for LRRK2 G2385R and R1628P variants and GBA L444P mutation. Participants were surveyed with structural questionnaires for history of environmental exposure and living habits and interviewed to collect the time at onset of each symptoms before diagnosis. We compared the cumulative prevalence and manifestation pattern of symptoms between groups using multiple logistic regression, adjusting age and gender. RESULTS: Total 1799 PD patients were recruited, including 226 patients with LRRK2 G2385R or R1628P variant, 44 with GBA L444P mutation, three with both LRRK2 and GBA mutation, and 1526 idiopathic patients. The cumulative prevalence of non-motor and typical motor symptoms did not differ between groups before diagnosis (P > 0.05). The manifestation sequences of non-motor symptoms were indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD subjects, and followed the sequence of constipation, hyposmia, sleep disorders, anxiety and depression, sexual dysfunction, urinary incontinency, dizziness and cognition. Slightly higher prevalence of hypomimia and micrographia were detected in the GBA-carriers. CONCLUSIONS: The prevalence of pre-diagnostic symptoms is almost indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD before diagnosis; the sequence of the manifestation of non-motor symptoms largely conforms to the Braak stage for both genetic-related and idiopathic late-onset PD.