Kenji Nakashima

Utility of the REM sleep behavior disorder screening questionnaire (RBDSQ) in Parkinson's disease patients.

OBJECTIVEnWe evaluated the usefulness of the REM sleep behavior disorder (RBD) screening questionnaire (RBDSQ) among patients with Parkinsons disease (PD).nnnMETHODSnForty-five patients with PD were evaluated (22 male and 23 female, 72.9±9.1 years old). After patients completed the RBDSQ, we conducted interviews regarding RBD symptoms and performed polysomnographic examinations on the subjects. We then compared RBDSQ scores among the following groups: PD with RBD (n=19), PD without RBD (n=26), and idiopathic RBD (n=31, 22 male and 9 female, 67.8±6.5 years old), and estimated the cut-off score for an RBD diagnosis.nnnRESULTSnRBDSQ scores in PD with RBD and idiopathic RBD groups were similar and higher than those in the PD without RBD group (PD with RBD: 7.2±1.9, idiopathic RBD: 7.9±2.8, PD without RBD: 2.9±1.6). Cronbachs α for RBDSQ sub-scores was 0.73, suggesting a fair internal consistency. A receiver-operator characteristics curve revealed that a total score of 6 points on the RBDSQ represented the best cut-off value for detecting RBD (sensitivity=0.842, specificity=0.962).nnnCONCLUSIONnRBDSQ could be a useful tool for the screening of RBD in PD patients.

Clinical significance of REM sleep behavior disorder in Parkinson’s disease

OBJECTIVEnRapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for dementia development in patients with Parkinsons disease (PD); however, the role of subclinical RBD remains unknown. Patients with PD and clinical RBD, subclinical RBD, or with normal REM sleep were examined in a cross sectional study and a longitudinal follow-up.nnnMETHODSnInterviews regarding RBD symptoms and polysomnographies were performed on 82 PD patients divided into RBD subcategories based on the presence/absence of REM sleep without atonia (RWA) and/or RBD symptoms. Descriptive variables were compared and patients were followed-up longitudinally for 21.4±10.8months.nnnRESULTSnThe existence of RBD, but not subclinical RBD, was associated with orthostatic hypotension and levodopa dose equivalents (LDEs) in patients with PD. Kaplan-Myer curves indicated that the occurrence of dementia in the PD group with clinical RBD was significantly faster than in the PD group with normal REM sleep (p=0.013). A Cox hazard regression analysis revealed that development to PD with dementia was only significantly associated with the presence of clinical RBD (hazard ratio: 14.1, p=0.017).nnnCONCLUSIONnClinical RBD symptoms, but not subclinical RBD, were associated with the development of dementia in PD.

Multicentre population-based dementia prevalence survey in Japan: a preliminary report

Community‐based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimers disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5‐year age strata between 65 and 99u2003years was 5.8–77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011–2012.

Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimers disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

Comparison of REM sleep behaviour disorder variables between patients with progressive supranuclear palsy and those with Parkinson’s disease

PURPOSEnRapid eye movement (REM) sleep behaviour disorder (RBD) is an important indicator of underlying synucleinopathies. However, the frequency of RBD in tauopathies such as progressive supranuclear palsy (PSP) remains unclear. In this study, we compared RBD-related symptoms and polysomnographic (PSG) findings between patients with PSP and those with Parkinsons disease (PD).nnnMETHODSnWe conducted clinical interviews of 20 patients with PSP, 93 patients with PD and their caregivers regarding RBD-related symptoms, and conducted PSG recordings on all the subject patients. We then compared the clinical backgrounds, PSG parameters, and frequency of RBD-related symptoms between the two groups.nnnRESULTSnPSP patients had more severe symptoms of Parkinsonism and cognitive impairment, and took lower doses of dopaminergic agents compared with PD patients. The PSP group had lower values for both estimated total sleep time and sleep efficiency on PSG compared with the PD group (p = 0.002, p = 0.021, respectively). The PSP group also included a significantly smaller number of patients having REM sleep without atonia (RWA) compared with the PD group (n = 5, 20.0% vs. n = 56, 60.2%, p = 0.003). None of the PSP patients were experiencing RBD-related symptoms at the time of the investigation, while 30 PD patients (32.3%) had RBD-related symptoms.nnnDISCUSSIONnThe existence of RWA as well as RBD-related symptoms was less frequent in patients with PSP versus patients with PD. Differences in brain stem pathology and/or disease course between the two disorders might influence this difference.

Prevalence of Dementia and Mild Cognitive Impairment in the Rural Island Town of Ama-cho, Japan

Aims: In order to determine the prevalence of dementia and mild cognitive impairment (MCI), we conducted a population-based study in Japan. Methods: Participants included 924 subjects aged 65 years or older who resided in the town of Ama-cho. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2 of the study, the subjects who screened positive were further examined by neurologists. Dementia and MCI were diagnosed by means of DSM-IV and International Working Group on MCI criteria, respectively. Results: By the prevalence date of June 1, 2010, 24 subjects had deceased or lived outside the town. In total, 723 of the remaining 900 subjects received a phase 1 test. In phase 2, 98 subjects were diagnosed with amnestic MCI, 113 subjects with non-amnestic MCI, and 82 subjects with dementia. Of the subjects who did not receive the phase 1 test, 66 subjects were diagnosed as having dementia according to data from their town medical card or the Long-term Care Insurance System. The crude prevalence of amnestic MCI, non-amnestic MCI, and dementia were 10.9, 12.6, and 16.4%, respectively. Conclusion: Consistent with the striking increase in the number of elderly individuals, we report higher prevalence of MCI and dementia in Japan than previously described.

Characteristics of obstructive sleep apnea in patients with Parkinson's disease

Parkinsons disease (PD) patients frequently develop obstructive sleep apnea (OSA). In order to clarify the clinical significance of OSA in PD, we compared descriptive variables between PD patients with OSA (PD+OSA) and without (PD-OSA), and between the PD+OSA group and a group of OSA patients without PD (control OSA). The apnea hypopnea index (AHI) cutoff of 15 episodes/hour on polysomnogram (PSG) was used to assign 107 PD patients to groups; OSA-related symptoms and PSG findings were then compared. Demographic and PSG variables were compared between PD+OSA patients and 31 OSA controls. Twenty-four patients with PD (22.4%) were classified as PD+OSA. There were no significant differences in descriptive variables between the PD+OSA and PD-OSA groups. The PD+OSA group had a higher arousal index on PSG than the PD-OSA group, although the two groups had similar ESS scores. The PD+OSA patients had a lower respiratory arousal index and a smaller decrease in oxygen saturation than the control OSA group, despite having a similar AHI. The prevalence of OSA in PD did not differ from that in the general elderly population, indicating that the clinical significance of OSA as a contributor to daytime sleepiness in PD is low.

Depression and cognitive impairment in patients with mild parkinsonian signs

Mild parkinsonian signs (MPS) are reported to be associated with increased risk of dementia, Parkinsons disease, parkinsonism, and vascular lesions of white matter and are also a significant predictor of mortality. Although more than 20% of subjects aged 60 years and older suffer from MPS in Japan, it is often unrecognized and underestimated by patients and medical physicians. We used neuropsychological methods to examine cognitive function and depressive symptoms in subjects with MPS.

A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan

BackgroundOnly a few prospective studies have determined which clinical symptoms and factors are associated with the disease severity of spinocerebellar ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to clarify both the natural history of SCA6 in Japan and the factors influencing disease progression.MethodsPatients were consecutively recruited between 2007 and 2008. Scores from the Scale for the Assessment and Rating of Ataxia (SARA) and Barthel Index (BI) were collected prospectively each year. Additionally, data from the Japan intractable diseases research (IDR) registry were collected both retrospectively, from 2003 to 2006, and prospectively, from 2007 to 2010. As a result, we were able to collect 3xa0years of retrospective data and 4xa0years of prospective data during the course of 3 yearly visits.ResultsForty-six patients were registered. The follow-up rate of the third year was 93%. The SARA scores worsened significantly each year. Over 3xa0years, the decline of the SARA scores was 1.33u2009±u20091.40 points/year. The results of multivariate analysis of the decline of the SARA score were not significant. The IDR scores correlated well with the SARA and BI scores. Kaplan-Meier curves of 7xa0years of data from the IDR registry illustrated the correlation between the ability to walk and the time course of the disease.ConclusionsInformation regarding the progression of ataxia and the decline in the activities of daily living (ADL) in patients with SCA6 was obtained by a 3-year cohort study and a 7-year IDR study. The decline of the SARA score of patients with SCA6 was 1.33u2009±u20091.40 points/year. The results elucidate the natural history of SCA6, factors influencing disease severity, and utility of data from the IDR registry of Japan.

Association of cerebral white matter lesions with cognitive function and mood in Japanese elderly people: a population-based study

To determine the relationships between regional white matter lesions (WMLs), lifestyle factors, and cognitive, motor function and mood.