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Background The Neuropsychiatric Inventory (NPI) is a widely used scale for the assessment of the behavioral and psychological symptoms of dementia (BPSD). We previously developed a novel dementia scale, the ABC dementia scale, in the TRIAD1412 trial and we compared the BPSD domain scores with the NPI scores. We, therefore, considered that we should investigate the quality of the NPI items using statistical approaches. Objective We investigated the statistical characteristics of the 12 questions or items in the Japanese version of the NPI using the item response theory. This theory is the standard approach for the development of a new assessment scale and we used it to evaluate the quality of the items in the NPI. Methods First, we performed factor analysis with Promax rotation to identify latent constructs in the data from 312 patients obtained in TRIAD1412. Second, following the result of the factor analysis, we divided the 12 items into domains and then investigated the characteristics of the sub-syndromes in each domain using item response category characteristic curves. Results We found three latent constructs or domains: "hyperactivity," "psychosis and apathy," and "affect" (Cronbach's α= 0.68) in the 12 items. Further, the items on euphoria, apathy, and appetite and eating abnormalities did not provide sufficient information to estimate BPSD severity. Conclusion The NPI item characteristics indicate that while the scale can distinguish whether patients have severe BPSD or not, it cannot estimate the degree of severity in a suspected case with a mild or unknown level of BPSD.

Objective We examined the benefits of a community‐based program combining physical exercise, cognitive training, and education on dementia and lifestyle habits. Methods This crossover open‐label trial included 141 community‐dwelling elderly people with suspected mild cognitive decline (MCD). Subjects were assigned to a 6‐month intervention‐first/6‐month observation‐second (INT‐OBS) group or an OBS‐INT group. The 6‐month intervention consisted of 2 h of physical exercise, cognitive training, and classroom study or rest once weekly. Primary outcome was change in Touch Panel‐type Dementia Assessment Scale (TDAS) score. Results TDAS score improved significantly during the intervention period compared with the observation period for all subjects (P

Background Mild parkinsonian signs are important clinical symptoms related to the decline of motor and cognitive functions. We aimed to identify predictors for the incidence of mild parkinsonian signs in older Japanese by conducting an 8-year longitudinal community-based cohort study. Methods Participants aged 65 years or older, living in Ama-cho, a rural island town in western Japan, underwent a baseline assessment of motor function, cognitive function, depression score, the Pittsburgh Sleep Quality Index (PSQI), the Tanner questionnaire, and cerebral white matter lesions on brain magnetic resonance imaging from 2008 to 2010, and then underwent a follow-up neurological examination from 2016 to 2017. Mild parkinsonian signs were defined according to a modified Unified Parkinson's Disease Rating Scale score. Results Of the 316 participants without mild parkinsonian signs at baseline, 94 presented with incident mild parkinsonian signs at follow-up. In addition to an absence of exercise habits, a higher score on the Tanner questionnaire, PSQI, and deep white-matter hyperintensity Fazekas scores were significant independent predictors for incidence of mild parkinsonian signs. Conclusion We suggest multiple factors related to incidence of mild parkinsonian signs. Vascular lesions and sleep disorders are associated with a pathogenesis of mild parkinsonian signs, the Tanner questionnaire is useful for early detection of subclinical mild parkinsonian signs, and exercise has a possibility of being associated with preventing onset of mild parkinsonian signs.

Many studies use the global clinical dementia rating (CDR) of 0.5 as a criterion for mild cognitive impairment, but past studies have not fully discussed its validity. The authors developed the ABC Dementia Scale (ABC-DS) to accurately monitor the changes in activities for daily living, behavioral and psychological symptoms of dementia, and cognitive function. When we carried out a cluster analysis of ABC-DS scores of 110 individuals for whom global CDR was 0.5, there were three groups with different levels of activities for daily living and cognitive function. O'Bryant et al. proposed a new guideline to stage dementia using the CDR sum of boxes scores (CDR-SOB). We used their proposal and ABC-DS scores to evaluate the validity of CDR 0.5 as a definition of mild cognitive impairment (MCI). We concluded that the CDR-SOB scores and ABC-DS score are more accurate than global CDR of 0.5 for specifying individuals with MCI.

Background: Alzheimer’s disease dementia (ADD) is the leading cause of long-term care in Japan. Objective: This study estimates the annual healthcare and long-term care costs in fiscal year 2018 for adults over 65 years of age with ADD in Japan and the informal care costs and productivity loss for their families. Methods: Healthcare and long-term care costs for ADD were estimated according to the disease severity classified by the clinical dementia rating (CDR) score, using reports from a literature review. For the costs of time spent on caregiving activities, productivity loss for ADD family caregivers aged 20–69 and informal care costs for all ADD family caregivers were estimated. Results: The total healthcare cost of ADD was JPY 1,073 billion, of which 86% (JPY 923 billion) was attributed to healthcare costs other than ADD drug costs (JPY 151 billion). The healthcare costs other than ADD drug costs by severity were less than JPY 200 billion for CDR 0.5, CDR 1, and CDR 2, respectively, but increased to JPY 447 billion (48%) for CDR 3. The public long-term care costs were estimated to be JPY 4,783 billion, which increased according to the severity. Total productivity loss for ADD family caregivers aged 20–69 was JPY 1,547 billion and the informal care cost for all ADD family caregivers was JPY 6,772 billion. Conclusion: ADD costs have a significant impact on public-funded healthcare, long-term care systems, and families in Japan. To minimize the economic burden of ADD, prolonging healthy life expectancy is the key factor to address.

AIM The present study aimed to assess the interrater reliability and construct the validity of a novel, convenient informant-based Alzheimer's disease assessment scale to prepare its final version. METHODS For the assessment, site investigators, co-medicals and, if available, medical staff other than doctors or co-medicals interviewed study informants to assess individuals using this scale. We then analyzed the interrater reliability and construct validity using factor analysis and item response characteristics. RESULTS In this study, 427 eligible participants were enrolled. We first examined the interrater reliability, and found that the lower limit of the confidence interval of each item was never

Background and aims The relationship between exercise and subcortical gray matter volume is not well understood in the elderly population, although reports indicate that exercise may prevent cortical gray matter atrophy. To elucidate this association in the elderly, we measured subcortical gray matter volume and correlated this with volumes to exercise habits in a community-based cohort study in Japan. Methods Subjects without mild cognitive impairment or dementia (n = 280, 35% male, mean age 73.1 ± 5.9 years) were evaluated using the Mini-Mental State Examination (MMSE), an exercise habit questionnaire, and brain magnetic resonance imaging. Subcortical gray matter volume was compared between groups based on the presence/absence of exercise habits. The MMSE was re-administered 3 years after the baseline examination. Results Ninety-one subjects (32.5%) reported exercise habits (exercise group), and 189 subjects (67.5%) reported no exercise habits (non-exercise group). Volumetric analysis revealed that the volumes in the exercise group were greater in the left hippocampus (p = 0.042) and bilateral nucleus accumbens (left, p = 0.047; right, p = 0.007) compared to those of the non-exercise group. Among the 195 subjects who received a follow-up MMSE examination, the normalized intra-cranial volumes of the left nucleus accumbens (p = 0.004) and right amygdala (p = 0.014)showed significant association with a decline in the follow-up MMSE score. Conclusion Subjects with exercise habits show larger subcortical gray matter volumes than subjects without exercise habits in community-dwelling elderly subjects in Japan. Specifically, the volume of the nucleus accumbens correlates with both exercise habits and cognitive preservation.

The course of Alzheimer's disease (AD) varies between individuals, and the relationship between cognitive and functional decline and the deterioration of behavioral and psychological symptoms of dementia (BPSD) is still poorly understood. Until recently, it was challenging to monitor subsequent changes in these symptoms because there was no single composite scale available that could simultaneously evaluate activities of daily living (ADL), BPSD, and cognitive function (CF) states. The present authors developed a new, brief assessment scale, the "ABC Dementia Scale" (ABC-DS), which is based on item response theory and facilitates concurrent measurement of ADL, BPSD, and CF states. We previously presented the reliability, construct validity, concurrent validity, and responsiveness of the ABC-DS. We obtained the evidence through three clinical trials featuring 1,400 subjects in total. In the present study, we performed a secondary analysis of the data obtained in the previous study. We conducted hierarchical cluster analyses that allowed us to classify 197 AD patients in terms of similarities regarding ADL, BPSD, and CF domain scores, as measured by the ABC-DS. Consequently, the scale identified subgroups of patients with global clinical dementia ratings of 1, 2, and 3. Considering our results in conjunction with the clinical experiences of the AD expert among the present authors regarding longitudinal changes in ADL, BPSD, and CF, we were able to propose potential progression pathways of AD in the form of a hypothetical roadmap.

Background Patients with non-demented Parkinson's disease (PD) sometime have mild cognitive impairment (MCI), and mild cognitive impairment in Parkinson's disease (PD-MCI) may convert to Parkinson's disease with dementia (PDD) within several years. Cognitive impairment also occurs in the early stages of the disease, gradually progressing to lower quality of life and instrumental activities of daily living. It is important to elucidate the predictors of progression from PD-MCI to PDD via longitudinal studies. Methods This was a single center, case-control study. We analysed data from 49 patients with PD-MCI diagnosed as level I using the Movement Disorder Society PD-MCI criteria at baseline who had completed 1.5 years of follow-up. We defined patients who progressed to PDD as patients with progressive PD-MCI and patients who did not progress to PDD as patients with non-progressive PD-MCI. Depression, apathy, sleep disorders, constipation, light-headedness, hallucinations, impulse control disorders (ICDs) and impulsive-compulsive behaviors (ICBs) at baseline were statistically analysed as predictors of progression. Results Of the 49 PD-MCI patients, 33 did not convert to PDD (non-progressive PD-MCI), and 16 converted to PDD (progressive PD-MCI). The Mini-Mental State Examination (MMSE) score, light-headedness and ICDs were elucidated as predictors of progressive PD-MCI via a multivariate logistic regression model. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each item were MMSE score, OR 0.324, 95% CI 0.119-0.882, P = 0.027; light-headedness, OR 27.665, 95% CI 2.263-338.185, P= 0.009; and ICDs, OR 53.451, 95% CI 2.298-291.085, P = 0.010. Conclusion Cognitive function, ICDs and light-headedness may be risk factors for the development of PDD in PD-MCI patients.

We aimed to clarify the longitudinal course of mild parkinsonian signs (MPS) and their association with dementia and functional disability by conducting a comprehensive epidemiological study, including brain MRI, and assessments of cognition, depression, and sleep, in people aged ≥65years living in Ama-cho. We diagnosed MPS and parkinsonism (PS) using a modified Unified Parkinson's Disease Rating Scale. The phase I study was conducted between 2008 and 2010 (n=729) and the phase II between 2011 and 2013 (n=436). By phase II, 8.5% of the phase I participants without PS had developed PS. In addition to older age, a lower Mini-Mental State Examination (MMSE) score, and lower body mass index, the MPS rigidity subtype was a significant independent predictor of PS onset. By phase II, 10.1% of the participants without dementia or PS at phase I had developed dementia. Older age, lower MMSE score, and the axial dysfunction and tremor MPS subtypes were significant independent predictors of dementia development. By phase II, 38.8% of participants with MPS at phase I showed no motor symptoms. Younger age and adequate sleep were significant predictors for this reversion. Periventricular and deep white matter hyperintensity Fazekas scores increased with the evolution of parkinsonian signs. MPS is therefore critically, although sometimes reversibly, associated with PS and dementia development in elderly people.

Aim The present study aimed to assess the interrater reliability and construct the validity of a novel, convenient informant‐based Alzheimer's disease assessment scale to prepare its final version. Methods For the assessment, site investigators, co‐medicals and, if available, medical staff other than doctors or co‐medicals interviewed study informants to assess individuals using this scale. We then analyzed the interrater reliability and construct validity using factor analysis and item response characteristics. Results In this study, 427 eligible participants were enrolled. We first examined the interrater reliability, and found that the lower limit of the confidence interval of each item was never

We provide a general overview of pharmacologic treatments for different types of dementia in light of the Guidelines on the Clinical Management of Dementia in Japan 2017, clinical data not addressed in those guidelines, and the results of observational studies, focusing mainly on the treatment of Alzheimer-type dementia. In everyday clinical practice, patients must be provided with personalized treatment that strikes a balance between evidence-based treatment, as described in the guidelines and actual clinical circumstances.

Objective: We established the diagnostic accuracy of the “ABC Dementia Scale” (ABC-DS) for Alzheimer’s disease (AD), which concurrently assesses activities of daily living (“A”), behavioral and psychological symptoms of dementia (“B”), and cognitive function (“C”), using a novel scoring approach called the three-dimensional distance (TDD). Methods: The ABC-DS has 13 items with nine ordered categorical levels. Caregivers were interviewed using a semi-structured interview. The construct validity, concurrent validity, test-retest reliability, and responsiveness (score changes over 12 weeks) were assessed. Results: We enrolled 63 participants with probable AD as well as 88, 106, and 55 patients with mild, moderate, and severe AD, respectively. The construct and concurrent validities of each domain score were determined. The TDD accurately discriminated the AD stages and detected score changes indicating disease progression over 12 weeks. Conclusion: The ABC-DS is stable, accurately stages AD severity, and monitors disease progression. The TDD is a useful algorithm for detecting disease progression.

Background: In this study, we examined the construct validity, concurrent validity concerning other standard scales, intrarater reliability, and changes in scores at 12 weeks of the previously developed ABC Dementia Scale (ABC-DS), a novel assessment tool for Alzheimer’s disease (AD). Methods: Data were obtained from 312 patients diagnosed with either AD or mild cognitive impairment. The scores on the ABC-DS and standard scales were compared. Results: The 13 items of the ABC-DS are grouped into three domains, and the domain-level scores were highly correlated with the corresponding conventional scales. Statistically significant changes in assessment scores after 12 weeks were observed for the total ABC-DS scores. Conclusion: Our results demonstrate the ABC-DS to have good validity and reliability, and its usefulness in busy clinical settings.

Background Fatigue is a common nonmotor symptom of Parkinson's disease (PD). Although the causes of fatigue were estimated in the previous reports, fatigue is not fully understood. To determine the frequency of and factors related to fatigue in patients with PD, we carried out clinical assessments in our university hospital. Methods We used the Japanese version of the Parkinson Fatigue Scale (J-PFS). The J-PFS was administered to 110 patients with PD, and a cutoff point of 3.3 was used for the diagnosis of fatigue. Subsequently, demographic characteristics, clinical features, and medications utilized were evaluated to elucidate the factors related to fatigue. In particular, we focused on the relationship between fatigue and gait disorder assessed via the portable gait rhythmogram. Results The frequency of fatigue in patients with PD was 52.7%. Univariate analysis revealed that factors significantly associated with fatigue were many motor symptoms and nonmotor symptoms. In addition, multivariate analysis revealed that gait disorder and constipation were independent factors related to fatigue. Furthermore, short-step walking and bradykinesia in gait disorder had especially a relationship with fatigue. Conclusions More than half of our patients were judged having fatigue. Several factors, including motor and nonmotor symptoms, might be related to fatigue in patients with PD.

Objective To clarify the clinical features of freezing of gait (FOG) in Parkinson's disease (PD) patients by classification into two groups: Clinically observed FOG (CFOG) and self‐reported FOG (SFOG). Methods Two hundred twenty‐nine PD patients were medically examined in an examination room as well as subjected to a New Freezing of Gait Questionnaire (NFOG‐Q) and analysis of nonmotor symptoms including sleep, cognition, depression, and fatigue. Results The prevalence of CFOG was 17.9%, while 53.7% of the patients without CFOG reported the presence of FOG via the NFOG‐Q. Univariate analysis revealed that CFOG was associated with longer disease duration, motor dysfunction, sleepiness, fatigue, and cognitive dysfunction. These symptoms, excluding akinesia, apathy, rapid eye movement (REM) sleep Behavior Disorder, and cognitive dysfunction, were also associated with SFOG. Multivariate analysis revealed that long PD duration, postural instability, and gait difficulty (PIGD), along with fatigue, were independent factors for SFOG. Conclusions SFOG and CFOG have many common clinical features. Although the clinical relevance of SFOG remains unclear, careful attention should be paid to related features in clinical practice.

Background Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is sometimes confused with Parkinson's disease, multiple system atrophy, and other disorders. The typical clinical features are categorized as Richardson's syndrome (RS), but other clinical subtypes include PSP-parkinsonism (PSP-P) and PSP-pure akinesia with gait freezing (PSP-PAGF). In this study, we determined the prevalence of PSP in a Japanese rural area compared to our previous 1999 report. Methods We collected data in Yonago City from 2009 to 2014 using a service-based study of PSP. We collected case history data from PSP patients in the area from our hospital. The crude prevalence and 95% confidence interval (CI) were calculated using the population demographics on the prevalence day of 1 October 2010. Age- and sex-adjusted prevalence was calculated by direct standardization to the population demographics in Yonago City on the prevalence day of 1 April 1999. Material and Results We identified 25 patients: 16 with probable RS, 4 with possible RS, 3 with clinical PSP-P, and 2 with clinical PSP-PAGF. The prevalence per 100,000 was 17.90 (male = 18.05; female = 17.76). The prevalence of PSP in Yonago in 2010 increased compared to the measurements from 1999. Conclusion The prevalence of PSP in Japan increased from 1999 to 2010.

Background: The prevalence of frontotemporal lobar degeneration (FTLD) in Japan is unknown. An epidemiological survey study of FTLD was undertaken in Tottori Prefecture, a district in the western region of Japan. Methods: Hospitals in Tottori Prefecture were surveyed by a two-step questionnaire in 2010, and the prevalence of FTLD per 100,000 inhabitants was calculated using the actual number of patients and inhabitants in Tottori Prefecture on the prevalence day of October 1, 2010. Results: In this survey, 66 patients were diagnosed with FTLD. The subtypes of FTLD were as follows: 62 cases of frontotemporal dementia (FTD), 3 cases of progressive nonfluent aphasia, and 1 case of semantic dementia. Among the FTD cases, 5 cases were FTD with motor neuron disease and 1 case was FTD with parkinsonism linked to chromosome 17. The prevalence of FTD in the total population of Tottori Prefecture was 11.2 per 100,000 inhabitants. Based on these results, the prevalence of FTLD in Japan in 2008 was estimated to be 9.5 per 100,000 individuals. Conclusions: Our epidemiological survey results suggest that there are at least 12,000 FTLD patients in Japan, indicating that FTLD is not a rare disease.

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.

Background and purpose: We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients. Methods: Fifty-eight MSA patients were recruited in our institution between April 1996 and December 2006 and investigated. Results: Of 58 patients, 10 were diagnosed with dementia. There were no significant differences in age at onset, gender, duration of disease, or severity of cerebellar dysfunction between patients with and without dementia. The early and delayed heart to mediastinum (H/M) ratios obtained with 123I-metaidobenylguanidine (MIBG) cardiac scintigraphy were significantly decreased in patients with dementia compared with those without dementia. Of the 10 patients with dementia, three were found to have cognitive decline that preceded onset of motor symptoms. White matter lesions were evident in these patients, whilst frontal atrophy was prominent in patients whose cognitive decline was preceded by onset of motor symptoms. Conclusions: Dementia in patients with MSA may be more common than previously thought, furthermore, we speculate that clinical features of dementia in these patients might be heterogeneous.

Background and purpose: To conduct an epidemiological survey of acute encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in Tottori Prefecture, western area of Japan. Methods: A questionnaire survey on the annual number of patients aged 16 years or more with acute encephalitis from 2001 to 2005 was undertaken in 2006. Results: During the study period, 49 patients were diagnosed with acute encephalitis. The subtype of acute encephalitis was as follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis associated with collagen disease, one patient with viral encephalitis other than HSE, 20 patients with encephalitis with unknown causes. The service-based incidence rate of acute encephalitis was 19.0 per million person-years. The incidence rate of NHALE subtype was 4.7 per million person-years. Conclusions: Our epidemiological survey indicated an estimated 550 patients would develop NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.

Objective In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). Methods Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. Results Serum levels of H-FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of 123 I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. Conclusions Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients.

This study examined the diagnostic value of cerebrospinal fluid (CSF) markers and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD).CSF levels of amyloid beta1-42 (Abeta42) and 181-Thr phosphorylated tau (p-tau) were measured using enzyme linked immunosorbent assay (ELISA) kits. (123)I-MIBG cardiac scintigraphy was performed in patients with AD and DLB, and control (CTL) subjects.Increased CSF levels of p-tau in AD were found compared to DLB patients and CTL subjects (P0.01), but there was no significant difference in CSF levels of Abeta42 between AD and DLB patients. The early and delayed heart to mediastinum (H/M) ratios of (123)I-MIBG cardiac scintigraphy were significantly decreased in patients with DLB compared to AD patients and CTL subjects (P0.01). The receiver operating characteristic (ROC) analysis revealed that the diagnostic value of (123)I-MIBG cardiac scintigraphy was superior to that of CSF markers.(123)I-MIBG cardiac scintigraphy may be useful for discriminating between DLB and AD.

Objective – To assess hallucinations in Parkinson’s disease (PD), we developed a novel practical rating scale that evaluates five items including variety, frequency, and severity of hallucinations, caregiver burden levels, and psychiatric status at nighttime. Methods – Forty-one PD patients and their caregivers were examined regarding the status of the hallucinations associated with PD. Results – As a measure of internal consistency, the Tottori University Hallucination Rating Scale (TUHARS) has a Cronbach’s α of 0.88. Mini-Mental State Examination (MMSE) and Hoehn–Yahr stage were associated with the TUHARS scores in a multivariate regression analysis. Visual hallucinations are the most common. However, half of the patients who reported visual hallucinations also had other hallucinations. The scale scores in the PD patients with dementia (PDD) group were significantly greater than in the PD patients without dementia (PDnD) group. Conclusions – TUHARS appears to be a suitable and easily administered instrument for assessment of hallucinations in PD. PD patients experienced various kinds of hallucinations. Hallucinations may have a close relationship with cognitive decline in PD patients.

Background Parkinsonism is often observed in the elderly. To clarify the prevalence of parkinsonism-associated diseases and conditions, we conducted a population-based study in a rural island town in western Japan, Ama-cho. Methods Participants included 924 subjects aged 65 years or older residing in the town. Between 2008 and 2011, participants were assessed via standardized neurological examination scales, and Brain MRIs were carried out in 2010. Based on the results of assessment using the modified Unified Parkinson's Disease Rating Scale and a standardized neurological examination, participants were diagnosed as having parkinsonism or mild parkinsonian signs (MPS), or as displaying normal motor conditions (M-normal). Results Of the 729 participants screened, 70 subjects were diagnosed as having parkinsonism, corresponding to a crude prevalence rate of 9.6% (95% CI, 7.9–11.3%), while 167 MPS subjects (22.9%) and 492 subjects experiencing M-normal (67.5%) were observed. Parkinsonism was found in association with various diseases such as Vascular parkinsonism, Lewy body disease, Alzheimer's disease (AD), and idiopathic normal-pressure hydrocephalus. Among the subjects with dementia, the proportion with parkinsonism was higher in the non-AD dementia group. Conclusion(s) Parkinsonism occurs in association with several diseases in elderly people. Parkinsonism was also found to be commonly associated with cognitive impairment.

Background To determine the relationships between regional white matter lesions (WMLs), lifestyle factors, and cognitive, motor function and mood. Methods A comprehensive evaluation, including brain MRI, blood tests, the Unified Parkinson's Disease Rating Scale, the Mini Mental State Examination, and the Geriatric Depression Scale, was performed for people aged 65 years or older living in Ama-cho on October 1, 2009. Participants were classified by severity of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using the Fazekas score. Results Of 900 eligible participants, 688 (76.4%) were enrolled, including 303 men. Significant predictors of severe PVH were older age, lower low-density lipoprotein cholesterol (LDL-C) levels, elevated blood pressure (BP), cerebral infarction, and no current alcohol use. Significant predictors of severe DWMH were older age, lower 1,5-anhydroglucitol (1,5-AG) levels, elevated BP, cerebral infarction, and no current alcohol use. Higher cognitive function was associated with younger age, female sex, mild DWMH, more years of education, and higher high-density lipoprotein cholesterol levels. Depressive symptoms were associated with lower 1,5-AG levels, lower LDL-C levels, moderate to severe PVH, and no current alcohol use. Conclusions White matter lesions in elderly people were related to hypertension and impaired glucose tolerance. The severity of WMLs was associated with cognitive function and mood.

In recent years, Alzheimer's disease (AD) has increased in incidence in Japan and elsewhere, and the marketing of donepezil hydrochloride (Aricept®) has allowed for the treatment of AD. These circumstances have encouraged the development of and research in markers for the early diagnosis of AD. Currently, the measurement of phosphorylated tau protein in the cerebrospinal fluid is considered to provide the most reliable and useful diagnostic marker for AD. For this purpose, a screening test using a touch panel computer can be recommended. The results of our study also suggest that the analysis of acetylcholine receptor α7 genetic polymorphism may be useful as a marker in the treatment with acetylcholine esterase inhibitors.

Objectives – To investigate a possible implication of inflammatory processes in the development of dementia in cerebrovascular disease. Patients and methods – We examined the levels of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 26), ischemic cerebrovascular disease without dementia (CVD) (n = 11), vascular dementia (VD) (n = 11), and other neurological disorders (n = 21) using sensitive enzyme-linked immunosorbent assay. Results – The CSF concentrations of IL-6 were significantly elevated in patients with VD compared with those of patients with AD or CVD. Conclusion – The CSF IL-6 levels are increased in patients with VD, suggesting that inflammatory mechanisms may be involved in the development of cognitive decline in some patients with cerebrovascular disease. CSF IL-6 may be a biological marker for dementia in cerebrovascular disease.

Background In order to evaluate impulsive compulsive behaviors (ICBs), such as pathological gambling, compulsive sexual behavior, compulsive buying, compulsive eating, punding, and dopamine dysregulation syndrome (DDS) in Japanese Parkinson's disease (PD) patients, we constructed a Japanese version of the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's disease (J-QUIP) and evaluated the utility of the J-QUIP in Japanese PD patients. Methods J-QUIP was administered to 121 PD patients. Diagnoses of ICBs were made via interview of patients or their caregivers. Subsequently, in order to evaluate risk factors related to these conditions, we evaluated demographic and clinical characteristics, clinical features, and medications utilized. Results We were able to administer the J-QUIP to 118 of 121 PD patients (97.5%). Sensitivity and specificity of J-QUIP were similar to that reported for the original version of QUIP. In our study, the actual prevalence of each disorder diagnosed via interview was as follows: pathological gambling (6.5%), compulsive sexual behavior (3.2%), compulsive buying (3.2%), compulsive eating (3.2%), punding (6.5%), and DDS (2.2%). Significantly risk factors for these conditions were younger age (p = 0.047), earlier age of disease onset (p = 0.015), longer PD duration (p = 0.001), total levodopa equivalent dose (p = 0.006), and dosage of levodopa (p = 0.019). Conclusions We evaluated the prevalence of ICBs in Japanese PD patients along with factors associated with these behaviors via J-QUIP.

Objectives Mild parkinsonian signs (MPS) are reported to be associated with increased risk of dementia, Parkinson's 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. Methods We performed a population-based study in Ama-cho, a rural island town in western Japan. Participants included 951 subjects aged 65 years and older, 613 of whom completed all questionnaires, neurological examinations, and neuropsychological assessments and were included in the data analysis. Subjects were assessed for depression and subjective cognitive impairment using the Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and modified Unified Parkinson's Disease Rating Scale (mUPDRS). Results Of the 613 participants, 143 were diagnosed with MPS. GDS scores were significantly higher in the MPS group compared with the motor control group, while MMSE scores were significantly lower. Conclusions We demonstrated that MPS correlate with both depressive symptoms and cognitive impairment.

Mild parkinsonian signs (MPS) may represent the mild end of a disease spectrum that spans from normal aging to neurodegenerative diseases. We conducted a population-based study in a rural island town in western Japan, Ama-cho. Participants included 1129 subjects, aged 60 years and older, residing in the town. Participants were classified according to a modified Unified Parkinson's Disease Rating Scale (mUPDRS) score. MPS was determined to be present if any of the following conditions were met: (1) two or more mUPDRS ratings=1 [MPS-mild]; (2) one mUPDRS rating≥2; or (3) mUPDRS rest tremor rating≥1; [(2) and (3): MPS-severe]. Subjects wore a uniaxial accelerometer (Actiwatch), resulting in the measurement of actigraphic activity counts (AC). Of the 804 participants with complete data, 178 subjects (22.1%) were classified as demonstrating MPS. AC was significantly lower in the MPS-severe group compared with both the CTL and the MPS-mild groups. Diagnostic sensitivity for MPS-severe became 100% when we adopted a cutoff point of low physical activity, as measured by actigraphy, combined with the presence of subjective depression. We established the prevalence of MPS in a community-dwelling elderly population sample in Japan. Actigraphy may be a useful objective tool for screening MPS-severe.

It has been reported that the cholinesterase inhibitor, donepezil, improves cognitive decline in patients with Parkinson's disease dementia (PDD). However, this improvement was dominant for frontal lobe dysfunction, and the increase in the Mini-Mental State Examination (MMSE) score was minimal. We report a PDD patient with a decline of regional cerebral blood flow (rCBF) in the posterior cingulate cortex, precunei, and bilateral parietotemporal association cortex, as determined by single-photon emission computed tomography (SPECT) using the easy Z-scores imaging system (e-ZIS). Upon administration of donepezil, both the rCBF and MMSE score increased. The effectiveness of donepezil may vary based on the rCBF pattern in PDD.

Background: With the striking increase in the number of elderly people in Japan, dementia has not only become a medical but also a social issue. Methods: We studied the prevalence of dementing disorders in a rural island town of Japan (Ama-cho), using a door-to-door 2-phase design. Results: Of the 120 persons screened as having cognitive impairment, 104 people were diagnosed as having dementia. The prevalence (cases/100 persons aged 65 years and older) was 11.0 for all types of dementia, 7.0 for Alzheimer’s disease, 1.7 for vascular dementia, 0.53 for dementia with Lewy bodies, 0.74 for Parkinson’s disease dementia, 0.21 for progressive supranuclear palsy, 0.11 for frontotemporal lobar degeneration and 0.74 for other dementia. The overall prevalence was higher in women for Alzheimer’s disease and Parkinson’s disease dementia, and in men, for vascular dementia and dementia with Lewy bodies. Conclusion: We confirmed the overall prevalence of dementia in the elderly population aged 65 years and older to be 11.0. This finding is higher compared with previous reports in Japan.

Background/Aims: Alzheimer’s disease (AD) is a well-known type of dementia. However, it remains difficult to identify AD in the early stage and to distinguish it from other dementing disorders. We examined glycoproteins in cerebrospinal fluid (CSF) as potential biological markers of AD. Methods: CSF samples were collected from AD, other dementia and nondemented patients. Glycoproteins in CSF were detected by lectin blotting using wheat germ agglutinin (WGA), and sugar chain analysis was performed by isoelectric focusing. Results: In Alzheimer’s CSF, several glycoproteins had lower WGA-binding activities, one of which was sufficiently sensitive and specific to distinguish AD from nondemented controls and other dementias. Further analysis identified this glycosylated protein as transferrin, and altered sugar chain composition of transferrin isoforms was observed despite normal protein levels in CSF. Conclusion: The decreased WGA-binding activity of transferrin in AD is probably due to altered glycosylation of transferrin molecules. Transferrin glycosylation is thus a potential biological marker for AD diagnosis, and changes in this glycosylation may play an important role in the pathophysiology of AD.