An analysis of the contents of the young-onset dementia helpline: profiles of clients who consulted the helpline themselves.

BACKGROUND: Young-onset dementia (YOD) community care requires personalised approaches. Yet, the specific details of YOD consultations are unclear. This study explored how initial consultations correlate with client profiles. METHODS: Data from regional YOD helplines were used to analyze the main characteristics of people living with YOD or who had concerns about the possibility of YOD (n = 132). Among several categorical variables, the following were used for analysis: age group, sex, type of living arrangement, employment status, presence of dementia, and content of the consultation. To identify groups of items that frequently occur together, strongly connected rules were identified using association rule analysis with the a priori algorithm. To focus on the characteristics of clients, rules related to client characteristics were extracted based on the type of consultation. RESULTS: A total of 51 rules were identified for the consultations. These rules fell into two categories: (1) consultations for medical matters, which mainly involved employed individuals with undiagnosed dementia, and (2) other consultations on daily life or work, which mainly involved individuals diagnosed with dementia and were characterised by the influence of sex. These rules indicate the importance of medical involvement in confirming the diagnosis and specific individualised care following diagnosis for people living with YOD. CONCLUSION: Clients with or without a dementia diagnosis were consulted differently in the YOD helplines. Before receiving a diagnosis, medical matters were the main theme of consultations, whereas after receiving a diagnosis, adjustments to daily life or work were the main themes. The results of this study suggest that the needs of people living with YOD and the services they require may vary depending on their backgrounds.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

A new educational tool for neuropsychological test raters in the dementia field: A Delphi study.

BACKGROUND: Neuropsychological testing is the primary endpoint of clinical research in the field of dementia, making it essential for the rater to accurately calculate test data for an extensive assessment. However, many raters lack adequate skill to complete neuropsychological tests with sufficient confidence. Therefore, we developed and examined the utility of a checklist and a manual as tools for educating raters on their basic behaviours when conducting comprehensive neuropsychological evaluations in the field of dementia. METHODS: We conducted a seven-step comprehensive study to develop rater training tools and examine their usefulness between April 2019 and February 2021 involving: 1. Development of a draft checklist, 2. Delphi review rounds, 3. Design of the final checklist, 4. Item weighting, 5. Examination of reliability, 6. Creating the manual, and 7. Examination of the usefulness of learning through rater educational tools (checklist and manual). RESULTS: The Delphi review round led to a highly reliable and valid checklist and manual. The total checklist score improved significantly (t = 2.37, P = 0.029) before and after manual learning. We found that the appropriate basic behaviours required by the rater to conduct neuropsychological testing skilfully within the dementia field could be acquired with this tool. CONCLUSIONS: Using a robust development process, we integrated expert knowledge and experience, and developed a checklist and a manual for learning the basic behaviours of neuropsychological test raters in the field of dementia. Establishing standards of basic behaviour for neuropsychological raters will help promote dementia research and advances in medicine.

An evaluation of the amyloid cascade model using in vivo positron emission tomographic imaging.

AIM: The amyloid cascade hypothesis posits that the accumulation of amyloid ß (Aß) is the triggering factor for Alzheimer's disease, which consecutively induces aggregation of tau, synaptic loss, and cell death. Most experimental and clinical evidence supports this model, but the available data are largely qualitative. Here, we tested the amyloid cascade hypothesis by using in vivo evaluation of positron emission tomography and magnetic resonance imaging. METHODS: Path analysis was used to estimate the relationships among Aß accumulation (PiB standardized uptake value ratio (SUVR)), tau aggregation and its related neuroinflammation (THK5351 SUVR), grey matter atrophy in the medial temporal region, and memory function in Aß-positive subjects. We also performed additional regression analyses to evaluate the effect of Aß on the toxicity of tau aggregation/neuroinflammation. RESULTS: Path analysis supported our hypothesized model: Aß accumulation affected tau aggregation/neuroinflammation in the medial temporal region, and these pathological changes caused of the grey matter atrophy and memory dysfunction. In separate regression analyses, THK5351 SUVR had a significant effect on grey matter atrophy only in PiB-positive subjects. The analysis of the interaction effect showed that the effects of THK5351 SUVR on grey matter atrophy were significantly different between PiB-positive and PiB-negative groups. When we included the effect of being an apolipoprotein E ε4 carrier as a covariate, the interaction effect remained significant. CONCLUSION: Our in vivo evaluation of positron emission tomographic and magnetic resonance imaging data supported the amyloid cascade hypothesis. In addition, it indicated that Aß not only accelerates tau aggregation/neuroinflammation but promotes its toxicity. Our findings showed the importance of understanding the role and therapeutic potential of the interaction between amyloid and tau aggregation/neuroinflammation in Alzheimer's disease.

Electromagnetic signatures of the preclinical and prodromal stages of Alzheimer's disease.

Biomarkers useful for the predementia stages of Alzheimer's disease are needed. Electroencephalography and magnetoencephalography (MEG) are expected to provide potential biomarker candidates for evaluating the predementia stages of Alzheimer's disease. However, the physiological relevance of EEG/MEG signal changes and their role in pathophysiological processes such as amyloid-ß deposition and neurodegeneration need to be elucidated. We evaluated 28 individuals with mild cognitive impairment and 38 cognitively normal individuals, all of whom were further classified into amyloid-ß-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-ß-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-ß-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-ß-negative cognitively normal (n = 25, mean age 72.5 ± 3.4 years, 11 males) individuals using Pittsburgh compound B-PET. We measured resting state MEG for 5 min with the eyes closed, and investigated regional spectral patterns of MEG signals using atlas-based region of interest analysis. Then, the relevance of the regional spectral patterns and their associations with pathophysiological backgrounds were analysed by integrating information from Pittsburgh compound B-PET, fluorodeoxyglucose-PET, structural MRI, and cognitive tests. The results demonstrated that regional spectral patterns of resting state activity could be separated into several types of MEG signatures as follows: (i) the effects of amyloid-ß deposition were expressed as the alpha band power augmentation in medial frontal areas; (ii) the delta band power increase in the same region was associated with disease progression within the Alzheimer's disease continuum and was correlated with entorhinal atrophy and an Alzheimer's disease-like regional decrease in glucose metabolism; and (iii) the global theta power augmentation, which was previously considered to be an Alzheimer's disease-related EEG/MEG signature, was associated with general cognitive decline and hippocampal atrophy, but was not specific to Alzheimer's disease because these changes could be observed in the absence of amyloid-ß deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer's disease.

Peak Work Rate during Exercise Could Detect Frailty Status in Elderly Patients with Stable Heart Failure.

The Kihon Checklist (KCL) is a reliable tool for determining frailty status in the elderly. However, there is no information in the literature about the relationship between frailty status and exercise capacity. Here, we examined the associations between cardiopulmonary exercise testing parameters and frailty status in elderly patients with stable heart failure (HF).Ninety-two elderly patients with stable HF were evaluated using cardiopulmonary exercise testing and the KCL. A KCL score of 0-3 was classified as robust, 4-7 as pre-frail, and ≥ 8 as frail.Mean age, peak VO2, and KCL score were 81.7 years, 13.2 mL/kg/minute, and 10.7, respectively. KCL score was significantly correlated with peak VO2 (r = -0.527, P < 0.001) and peak work rate (r = -0.632, P < 0.001). In patients with frailty (n = 63), the peak work rate (WR) was significantly lower than it was in patients without frailty (n = 29; 39.9 versus 69.5 W, respectively; P < 0.001). Multivariate analysis revealed that peak WR and peak systolic blood pressure were significant, independent predictors of frailty (ß = -0.108 and -0.045, respectively). In a diagnostic performance plot analysis, a cutoff value for peak WR of 51.9 W was the best predictor of frailty.Frailty status was significantly associated with peak WR and peak systolic blood pressure in elderly patients with stable HF. Therefore, cardiopulmonary exercise testing may be useful for assessing frailty status in this patient population.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

BACKGROUND AND PURPOSE: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD. METHODS: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline. RESULTS: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline. CONCLUSIONS: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested. TRIAL REGISTRATION NUMBER: UMIN00003419.

Novel plasma biomarker surrogating cerebral amyloid deposition.

Alzheimer's disease (AD) is the most common and devastating dementia. Simple and practical biomarkers for AD are urgently required for accurate diagnosis and to facilitate the development of disease-modifying interventions. The subjects for the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB-positive (PiB+) individuals, including cognitively healthy controls (HC), and mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB-) HC participated. Employing our novel highly sensitive immunoprecipitation-mass spectrometry, we measured plasma amyloid ß-proteins (Aßs; Aß1-40 and Aß1-42) and Aß-approximate peptides (AßAPs), which were cleaved from amyloid precursor protein (APP). Among the AßAPs, APP669-711 appeared to be a good reference for deciphering pathological change of Aß1-42. We evaluated the performance of the ratio of APP669-711 to Aß1-42 (APP669-711/Aß1-42) as a biomarker. APP669-711/Aß1-42 significantly increased in the PiB+ groups. The sensitivity and specificity to discriminate PiB+ individuals from PiB- individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely surrogates cerebral amyloid deposition.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Estimation of pathological lesion stage from brain images.

BACKGROUND: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a disease responsible for cognitive impairment in adult humans. It is caused by mutations in the colony stimulating factor 1 receptor gene (CSF1R) or alanyl-transfer (t) RNA synthetase 2 (AARS2) gene and affects brain white matter. Settlement of stages of the pathological brain lesions (Oyanagi et al. 2017) from the findings of brain imaging will be inevitably essential for prognostication. METHODS: MRI images of eight patients with ALSP were analyzed semiquantitatively. White matter degeneration was assessed on a scale of 0 to 4 (none, patchy, large patchy, confluent, and diffuse) at six anatomical points, and brain atrophy on a scale 0 to 4 (none, slight, mild, moderate, and severe) in four anatomical areas. The scores of the two assessments were then summed to give total MRI scores of 0-40 points. Based on the scores, the MRI features were classified as Grades (0-4). Regression analysis was applied to mutual association between mRS, white matter degeneration score, brain atrophy score, the total MRI score and disease duration. RESULTS: White matter degeneration score, brain atrophy score, and the total MRI score were significantly correlated with the disease duration. MRI Grades (2-4) based on the total MRI scores and the features of the images were well correlated with the pathological lesion stages (II - IV); i.e., 'large patchy' white matter degeneration in the frontal and parietal lobes (MRI Grade 2) corresponded to pathological Stage II, 'confluent' degeneration (Grade 3) to Stage III, and 'diffuse' degeneration (Grade 4) to Stage IV. CONCLUSION: MRI Grades (2-4) resulted from the total MRI scores were well correlated with the pathological lesion Stages (II - IV).

Neuropsychological differentiation between Alzheimer's disease and dementia with Lewy bodies in a memory clinic.

OBJECTIVE: The aim of this study was to identify a useful neuropsychological instrument for making a differential clinical diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: We examined 402 AD and 38 DLB patients with neuropsychological tests that covered general cognition, frontal lobe cognitive function, non-verbal abstract reasoning, working memory and attention, and verbal memory. Discriminant analysis using a stepwise method was performed to identify the measures best able to discriminate between AD and DLB. RESULTS: The AD patients performed significantly worse than the DLB patients on orientation to time, delayed recall subtests on the Mini-Mental State Examination, and logical memory subtests 1 and 2 of the Revised Wechsler Memory Scale. The DLB patients performed significantly worse than the AD patients on the attention, repetition, and pentagon copying subtests of the Mini-Mental State Examination, the constructional praxis subtests of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, the Frontal Assessment Battery total score, Raven's Coloured Progressive Matrices (RCPM) sets A, AB, and B, and backward digit span. Discriminant analyses between AD and DLB established the key variables as Logical Memory 1, Logical Memory 2, backward digit span, RCPM, and delayed recall on the Mini-Mental State Examination. We inferred the AD-DLB discriminant index from the following discriminant analyses: AD-DLB discriminant index = (Backward digit span score + RCPM set B score) - (Logical Memory 1 score + Logical Memory 2 score), which offered a highly favourable value for diagnostic utility. CONCLUSIONS: The AD-DLB discriminant index, consisting of backward digit span, RCPM set B, and logical memory 1 and 2, is useful to differentiate between AD and DLB.

Clinico-imaging features of subjects at risk of Lewy body disease in NaT-PROBE baseline analysis.

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson's disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome.

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Relationship between atrophy of the medial temporal areas and cognitive functions in elderly adults with mild cognitive impairment.

AIM: The current study sought to determine which types of cognitive function are related to atrophy of the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC) in elderly adults. METHODS: The subjects were 96 elderly adults (mean age 75.3 years) with mild cognitive impairment. Subjects underwent Wechsler Memory Scale-Revised, logical memory I and II (WMS-R, LM I and II), Rey complex figure retention tests after 3 and 30 min (RCF-3 min and RCF-30 min), digit span backword (DSB), digit symbol-coding (DSC), Stroop Color and Word Test-Interference List (SCWT-IL) as well as magnetic resonance imaging (MRI) and were divided into elderly adults without or with mild to moderate MTA-ERC atrophy, and those with severe atrophy. RESULTS: In all subjects, MTA-ERC atrophy showed significant relationships with age (r = 0.43), education (r = -0.25), WMS-R, LM I (r = -0.21), DSC (r = -0.32), and SCWT-IL (r = 0.32). The mild to moderate atrophy group showed significant relationships between MTA-ERC atrophy and age (r = 0.34), DSC (r = -0.28), and SCWT-IL (r = 0.25). In contrast, in the severe atrophy group, MTA-ERC atrophy was correlated significantly with RCF-3 min (r = -0.70) and RCF-30 min (r = -0.74). The linear regression model included demographic variables and cognitive tests; two variables to survive the step-wise analysis were age (ß = 0.374) and SCWT-IL (ß = 0.247) in all subjects. Age (ß = 0.301), and RCF-30 min (ß = -0.521) and age (ß = 0.460) remained as a significant variable in the mild to moderate atrophy and severe atrophy groups, respectively. CONCLUSION: Executive function tests such as SCWT-IL may be useful as a screening tool to identify mild to moderate MTA-ERC atrophy and a decline in the RCF test may suggest severe MTA-ERC atrophy in elderly adults with MCI.

The relationship between atrophy of the medial temporal area and daily activities in older adults with mild cognitive impairment.

BACKGROUND AND AIMS: Many studies have suggested that social network, leisure activity, and physical activity can have protective effects against dementia and Alzheimer's disease. However, previous studies have not examined the relationship between daily activities and brain atrophy in older adults. This study aimed to explore what kind of daily activities were associated with atrophy of the medial temporal area including the entorhinal cortex (MTA-ERC) in older adults. METHODS: In total, 122 older adults (aged 65 and over) with subjective memory complaints or a Clinical Dementia Rating of 0.5 underwent magnetic resonance imaging, and MTA-ERC atrophy was assessed by the voxel- based morphometry method. Based on magnetic resonance imaging data, the subjects were divided into atrophy and non-atrophy groups. Daily activities were assessed using a 20-item questionnaire (e.g., instrumental activities of daily living, social activities), and we compared activity participation between the groups. RESULTS: The atrophy group (n=37) showed significantly lower participation in 4 out of 20 activity items (cleaning, intellectual activity, culture lessons, and using a personal computer) than the non-atrophy group (n=85). Summed scores of these 4 items (range from 0 to 4) were significantly associated with MTA-ERC atrophy even after adjustment for age, sex, education status, and Mini-Mental State Examination score. CONCLUSIONS: In conclusion, MTAERC atrophy was associated with cognitive activities or household-related activities requiring planning.

[Oral conditions and oral management approaches in mild dementia patients].

AIM: The oral management of dementia patients is critical to prevent aspiration pneumonia and maintain patients' quality of life. However, the oral health status of these patients has not been adequately elucidated thus far, and it is not well understood how oral care is managed for mild dementia patients. To provide effective oral management for mild dementia patients, we investigated their oral health status and how their oral care was managed. METHODS: We enrolled 10 outpatients aged 66 to 85 years old who regularly visited our neurology clinic. All of the patients had mild dementia. We conducted 2 questionnaire studies regarding oral hygiene and dentures and performed an oral examination to evaluate the changes in oral hygiene status over time. The questionnaire was designed to explore the understanding of oral hygiene methods. Oral care instructions were given to the patients and their caregivers. Three surveys of 2 questionnaires each were performed. The survey was conducted at the initial visit, and 3 months and 6 months later. RESULTS: Although oral care instructions were given to the patients and their caregivers, neither their plaque index nor gingival index showed major improvement over time. Based on the results of these questionnaires, patient awareness of oral hygiene did not change over time. CONCLUSION: It is difficult for patients with mild dementia to perform oral care by themselves. It is important to make oral hygiene habits second nature in middle-aged patients, to introduce oral management to be performed by the caregivers and to promote early dental intervention to improve and maintain oral hygiene status in mild dementia patients.

Differentiating Dementia with Lewy Bodies from Alzheimer's Disease Using the Fall Risk Evaluation Questionnaire.

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.

Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum.

BACKGROUND: Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. OBJECTIVE: Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. METHODS: We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. RESULTS: On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. CONCLUSION: The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.

The association between decline in physical functioning and atrophy of medial temporal areas in community-dwelling older adults with amnestic and nonamnestic mild cognitive impairment.

OBJECTIVE: To examine whether declining performance in aspects of physical functioning, including lower extremity muscle strength, 1-legged balance, walking speed, and exercise capacity, is associated with atrophy of medial temporal areas in community-dwelling older adults with mild cognitive impairment (MCI). DESIGN: Cross-sectional study. SETTING: General community in Japan. PARTICIPANTS: Community-dwelling older adults 65 years and older with a Clinical Dementia Rating of 0.5 or memory complaints were enrolled in this study. This study examined 34 participants with amnestic MCI (aMCI) and 58 nonamnestic MCI (non-aMCI) participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The following physical performance tests were conducted: muscle strength of knee extension, 1-legged standing time, 5-m walking test, and 6-minute walk test (6MWT). The z scores of the voxel-based specific regional analysis system for Alzheimer's disease were determined to assess the degree of atrophy in the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC). RESULTS: In the aMCI group, 6MWT performance was associated with MTA-ERC atrophy (ß=-.462, P=.014) after controlling for age. In the stepwise multiple regression analyses, 6MWT and body mass index were found to be significant determinants of MTA-ERC atrophy in all participants (R(2)=.275), as well as the aMCI and non-aMCI groups when analyzed separately (R(2)=.418 and R(2)=.216, respectively). CONCLUSIONS: A decline in exercise capacity was found to be more closely associated with atrophy of the MTA-ERC compared with other aspects of physical functioning in older adults with MCI, especially the amnestic type. These findings suggest that it is important for future studies to investigate the effects of increased aerobic activity and improved fitness on brain volume in older adults at risk of developing dementia.

Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study.

INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.

Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure.

We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO2 narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN-1, PSEN-1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy.