Wheelchair dependence in patients with dementia: Focus on kinematic gait analysis using simple wearable accelerometers and gyroscopes.

Falls, wheelchair dependence, and bedridden status are the results of reduced mobility in the mid-late course of dementia. Kinematic gait analysis for patients with dementia is lacking because practically setting sensors on their bodies is particularly difficult. We analyzed the parameters of kinematic gait analysis that are related to the risks of wheelchair dependence in patients with dementia using wearable accelerometers and gyroscopes for detecting 3-dimensional physical movements. We collected data from 34 patients with dementia regarding demographics, cognitive function, CT scan findings, medications, and gait analysis parameters. The patients were followed up for 6 months. We compared data between dementia patients with and without wheelchair dependence by t-test or Fisher's exact test, multiple comparison, and simple logistic regression analysis for wheelchair dependence by gait analysis parameters. Eleven patients became wheelchair-dependent during the 6 months. The score on the clinical dementia rating scale was significantly higher and the hip extensor angle in walking was significantly lower in patients with dementia with wheelchair dependence than in those without. The severity of dementia and the lower angle of the hip extensor during walking may indicate the necessity of a wheelchair for patients with this disease.

A Novel Rhizobium sp. Chiba-1 Strain Exhibits a Host Range for Nodule Symbiosis in Lotus Species.

Rhizobia are soil bacteria that induce the formation of nodules in the roots of leguminous plants for mutualistic establishment. Although the symbiotic mechanism between Lotus japonicus and its major symbiotic rhizobia, Mesorhizobium loti, has been extensively characterized, our understanding of symbiotic mechanisms, such as host specificity and host ranges, remains limited. In the present study, we isolated a novel Rhizobium strain capable of forming nodules on L. burttii from agricultural soil at Iwate prefecture in Japan. We conducted genomic and host range ana-lyses of various Lotus species. The results obtained revealed that the novel isolated Rhizobium sp. Chiba-1 was closely related to R. leguminosarum and had a wide host range that induced nodule development, including L. burttii and several L. japonicus wild-type accessions. However, L. japonicus Gifu exhibited an incompatible nodule phenotype. We also identified the formation of an epidermal infection threads that was dependent on the Lotus species and independent of nodule organ development. In conclusion, this newly isolated Rhizobium strain displays a distinct nodulation phenotype from Lotus species, and the results obtained herein provide novel insights into the functional mechanisms underlying host specificity and host ranges.

Expansion of droplets during speaking and singing in Japanese.

During the COVID-19 pandemic, a number of infection clusters associated with choral singing have been reported. Singing generates droplets and carries the risk of spreading infection. However, no reports have explored droplet flight and aerosol production rates by singing and speaking in Japanese. First, we conducted an observation experiment evaluating the maximum flight distance and number of droplets generated by singing in Japanese, using a high-speed camera and particle counter. Twenty amateur choir members, 10 male and 10 female (five members for each of the four voices), participated in the experiment. Subsequently, although the maximum distance that droplets traveled by singing in Japanese was 61 cm for men (median of 46.5, interquartile range, 36-57) and 56 cm for women (median of 27.5, interquartile range, 20-50), droplets were observed anteriorly and laterally to be up to 66.8 cm. At the singer's mouth, ≥ 5 µm droplets were observed, whereas not observed at 1 meter toward the front of the singers in women and men, respectively. In German singing, droplets were observed up to 111 cm toward the front of the singer, possibly reflecting differences in pronunciation. In Japanese reading aloud, droplets were also observed up to 47 cm toward the front, whereas no droplet dispersion was observed by speaking the Japanese /a/ vowel or singing with wearing surgical mask toward the front. The aerosols produced when reading singing the /u/ vowels were significantly higher than those in other vowels. When singing in a choral group, keeping a sufficient distance at the front and side is recommended in minimizing infectious spread. If distance is not possible, practicing with /a/ vowels and avoiding consonants may be an alternative method. Our observations lasted only 50 seconds per song, and further observational studies are needed to determine the dynamics of aerosols that stay for long periods.

Genetic and demographic predisposing factors associated with pediatric sleepwalking in the Philadelphia Neurodevelopmental Cohort.

OBJECTIVES: Sleepwalking is a parasomnia associated with non-rapid eye movement (NREM) sleep and is formally diagnosed using polysomnography (PSG). However, PSG are difficult to perform on children or adolescents due to needed compliance. To understand this condition in youth, few studies have been conducted on a large cohort of youths with a diverse distribution of ages and races to characterize it better in the absence of PSG. The present study aimed to evaluate the prevalence of sleepwalking in youth, as well as associated demographic and genetic characteristics, using questionnaires in a large pediatric cohort. METHODS: Data from the Philadelphia Neurodevelopmental Cohort (PNC) of 7515 youths aged between 8 and 22 years were used in analyses. Demographic and clinical data, including age, sex, and race, and genetic data from 2753 African American (AA) and 4762 European American (EA) subjects were investigated. The age-wise prevalence of sleepwalking in AA and EA subjects was evaluated. Finally, race-specific genome-wide association (GWAS) analyses of sleepwalking were also performed (N = 155 AA cases and 2598 AA controls; N = 512 EA cases and 4250 EA controls). RESULTS: Lifetime history of sleepwalking correlated with male sex and EA race. A genetic risk locus that reached genome-wide significance was detected at rs73450744 on chromosome 18 in AA, but not EA youth. CONCLUSION: The present results suggest that male sex, EA race, and genetic factors may be associated with higher rates of sleepwalking among youth. Future studies should consider these variables to advance understanding of the complex pathogenesis of sleepwalking.

A Severe Dementia Case in End of Life Care with Psychiatric Symptoms Treated by Perampanel.

Epilepsy is known to comorbid with Alzheimer's disease. It can promote cognitive decline, and eventually worsen their prognosis and mortality. It is sometimes difficult to find a suitable drug because of the adverse effects. Perampanel has a unique mechanism of action that antagonizes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type glutamate receptor. Here, we report a case of severe dementia due to Alzheimer's disease with intractable epilepsy, which perampanel effected for controlling seizures with less adverse effects. The subject is an 89-year-old Japanese woman with severe dementia due to Alzheimer's disease and intractable myoclonic epilepsy. She also had psychiatric symptoms, such as circadian rhythm disorder and irritability. Valproic acid, lacosamide, or carbamazepine were prescribed, but none of them was effective. Shortly after perampanel started, however, myoclonus and these psychiatric symptoms improved. Moreover, it did not cause any obvious adverse effects, which made it possible to continue perampanel until the end of her life. Perampanel may be useful for controlling intractable epilepsy accompanied by Alzheimer's disease. It may also improve psychiatric symptoms with less adverse effect. Accumulation of studies is necessary to evaluate the effectiveness of perampanel on the epilepsy of Alzheimer's disease patients and further understand that mechanism.

Exploratory investigation on antibodies to GluN1 and cognitive dysfunction in patients with chronic autoimmune psychosis.

INTRODUCTION: Mild cognitive dysfunction has been implicated in a number of psychiatric diseases and affects social functioning. Although clinical criteria were recently proposed for autoimmune psychosis (AP), biomarkers have not yet been established for the severity and prognosis of cognitive dysfunction. We herein investigated the relationships between 3 types of serum antibodies and cognitive dysfunction in chronic psychiatric patients suspected of AP. METHODS: We included 31 patients suspected of AP and obtained information on their clinical characteristics. Three types of autoantibodies (the anti-N-methyl-D-aspartate receptor (anti-NMDAR Ab), anti-N-terminal of GluN1 (anti-GluN1-NT Ab), and anti-thyroid antibodies) were evaluated in serum. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. We examined the relationships between serum autoantibodies and cognitive dysfunction in patients using multiple regression models. RESULTS: Serum titers of anti-GluN1-NT Ab significantly contributed to the estimated score of working memory (B= -55.85, ß= -0.46, p= 0.01), while no correlation was observed between the other 2 types of antibodies and cognitive function. CONCLUSIONS: The present results indicate the potential of serum anti-GluN1-NT Ab as a biomarker for the severity and prognosis of cognitive dysfunction underlying various psychiatric symptoms in patients with AP. The pathological significance of anti-GluN1-NT Ab needs to be verified in future studies.

An exploratory investigation of antibodies to NMDA-type glutamate receptor subunits in serum and cerebrospinal fluid among psychiatric patients with anti-thyroid antibodies.

INTRODUCTION: Hashimoto's thyroiditis, which is characterized by anti-thyroid antibodies such as the anti-thyroglobulin (Tg) antibody and anti-thyroid peroxidase (TPO) antibody, is one of the autoimmune diseases associated with psychiatric illnesses. We previously reported a high prevalence of antibodies to N-terminals of N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN1-NT and GluN2B-NT2) among psychiatric patients with anti-thyroid antibodies. However, it remains unclear whether the presence of anti-thyroid antibodies influences antibodies to GluN1-NT or GluN2B-NT2 among psychiatric patients. The present study aims to examine antibodies to GluN1-NT and GluN2B-NT2 in psychiatric patients with anti-thyroid antibodies (PPATs) and in those without (non-PPATs). MATERIAL AND METHODS: We recruited psychiatric inpatients aged 20-60 years. Patients were excluded if they had a history of neurological diseases, dementia, developmental disorders, tumors, or autoimmune diseases except autoimmune thyroiditis. The rest of the participants were divided into two groups according to the presence of serum anti-Tg and anti-TPO antibodies. We investigated serum and cerebrospinal fluid (CSF) antibodies to GluN1-NT and GluN2B-NT2 using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We initially recruited seventy-three psychiatric inpatients. Forty-six patients were excluded because of the exclusion criteria. Eighteen PPATs and nine non-PPATs were ultimately enrolled. We also collected stored sera of eighteen healthy controls (HCs) who were age- and sex-matched with PPATs. The optical densities (ODs) of serum antibodies to GluN1-NT (p = 0.0020) and GluN2B-NT2 (p = 0.039) were significantly higher in PPATs than in HCs. The ODs of CSF antibodies to GluN1-NT (p = 0.030) and GluN2B-NT2 (p = 0.017) as well as the positive ratios of those antibodies were significantly higher in PPATs than in non-PPATs. CONCLUSION: Our finding indicates that detecting anti-thyroid antibodies in psychiatric patients would be a clue to consider psychiatric conditions related to antibodies to GluN1-NT/GluN2B-NT2. Further studies focusing on the relationship between PPATs and antibodies to GluN1-NT/GluN2B-NT2 are needed.

Influence of plasma matrix metalloproteinase levels on longitudinal changes in Alzheimer's disease (AD) biomarkers and cognitive function in patients with mild cognitive impairment due to AD registered in the Alzheimer's Disease Neuroimaging Initiative database.

OBJECTIVE: The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS: We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aß42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aß42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS: No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION: High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.

The Cingulate Island Sign on FDG-PET vs. IMP-SPECT to Assess Mild Cognitive Impairment in Alzheimer's Disease vs. Dementia with Lewy Bodies.

BACKGROUND AND PURPOSE: The cingulate island sign (CIS) on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET); ie, the relative preservation of mid-posterior cingulate cortex metabolism, is a supportive biomarker in the diagnostic criteria for dementia with Lewy bodies (DLB). However, limited information is currently available on the diagnostic value of the CIS on FDG-PET or 123 I-iodoamphetamine single-photon emission computed tomography (IMP-SPECT) for differentiating between mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (MCI-AD) and MCI due to DLB (MCI-DLB). METHODS: We examined the CIS ratio in 9 AD patients, 9 DLB patients, 8 patients with MCI-AD, and 9 patients with MCI-DLB using FDG-PET and IMP-SPECT. The CIS ratio was calculated using NEUROSTAT software. RESULTS: In the dementia groups, a receiver operating characteristic analysis of the CIS ratio showed significant accuracy for differentiating between AD and DLB on FDG-PET and IMP-SPECT. In the MCI groups, only the FDG-PET derived CIS ratio displayed significant accuracy for differentiating between AD and DLB. CONCLUSIONS: The FDG-PET and IMP-SPECT derived CIS ratios are both useful for differentiating between AD and DLB. The FDG-PET derived CIS ratio is more valuable than the IMP-SPECT derived CIS ratio for differential diagnosis in patients with MCI. A larger study is needed to confirm these results.

A case of treatable dementia with Lewy bodies remarkably improved by immunotherapy.

We report a case of probable dementia with Lewy bodies (DLB) with several findings indicating autoimmune encephalitis (e.g. anti-thyroid antibodies in serum and oligoclonal band and anti-N-methyl-d-aspartic acid receptor antibodies in cerebrospinal fluid). The symptoms and the findings of ancillary tests such as Iodine-123-metaiodobenzylguanidine myocardial scintigraphy and 99mTechnetium-ethyl-cysteinate-dimer single photon emission computed tomography were improved after the pulse and oral steroid treatment. This case is thought the autoimmune encephalitis mimicking DLB. This experience indicated the importance of suspecting treatable DLB even when the findings of laboratory and radiological tests fulfill the diagnostic criteria of DLB.

The cingulate island sign in patients with dementia with Lewy bodies or Alzheimer's disease: A direct comparison between 18F-FDG PET and 123I-IMP SPECT.

The cingulate island sign (CIS) on 18F-fluorodeoxyglucose positron emission tomography (FDG PET); i.e., the relative preservation of mid-posterior cingulate cortex metabolism, is a supportive biomarker in the diagnostic criteria for dementia with Lewy bodies (DLB). Information is lacking, however, regarding the diagnostic value of the CIS on FDG PET or 123I-iodoamphetamine single-photon emission computed tomography (IMP SPECT) for differentiating between mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (MCI-AD) and MCI due to DLB (MCI-DLB). We examined the CIS ratio for nine AD patients, nine DLB patients, eight patients with MCI-AD, and nine patients with MCI-DLB using FDG PET and IMP SPECT. The CIS ratio was calculated as the total count density for the mid-posterior cingulate cortex divided by the total count density for the precuneus and cuneus using the stereotactic extraction estimation method. In the dementia groups, receiver operating characteristic analysis of the CIS ratio showed significant accuracy for differentiating between AD and DLB on both FDG PET and IMP SPECT. In the MCI groups, only the FDG PET-derived CIS ratio displayed significant accuracy for differentiating between AD and DLB. A larger study is needed to replicate these findings.

An overview of hypocretin based therapy in narcolepsy.

INTRODUCTION: Narcolepsy with cataplexy is most commonly caused by a loss of hypocretin/orexin peptide-producing neurons in the hypothalamus (i.e., Narcolepsy Type 1). Since hypocretin deficiency is assumed to be the main cause of narcoleptic symptoms, hypocretin replacement will be the most essential treatment for narcolepsy. Unfortunately, this option is still not available clinically. There are many potential approaches to replace hypocretin in the brain for narcolepsy such as intranasal administration of hypocretin peptides, developing small molecule hypocretin receptor agonists, hypocretin neuronal transplantation, transforming hypocretin stem cells into hypothalamic neurons, and hypocretin gene therapy. Together with these options, immunotherapy treatments to prevent hypocretin neuronal death should also be developed. AREAS COVERED: In this review, we overview the pathophysiology of narcolepsy and the current and emerging treatments of narcolepsy especially focusing on hypocretin receptor based treatments. EXPERT OPINION: Among hypocretin replacement strategies, developing non-peptide hypocretin receptor agonists is currently the most encouraging since systemic administration of a newly synthesized, selective hypocretin receptor 2 agonist (YNT-185) has been shown to ameliorate symptoms of narcolepsy in murine models. If this option is effective in humans, hypocretin cell transplants or gene therapy technology may become realistic in the future.

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

OBJECTIVES: Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. METHODS: We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. RESULTS: Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. CONCLUSION: Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship.

41-fs, 35-nJ, Green Pulse Generation from a Yb-doped Fiber Laser System.

We report ultrafast green pulse generation from a Yb-doped fiber laser system with gain-narrowing compensation. The chirped-pulse amplification system outputs repetitive 3 MHz pulses with an energy of 35 nJ and a reconstructed pulse duration of 41 fs.

Characteristics of mild cognitive impairment tending to convert into Alzheimer's disease or dementia with Lewy bodies: A follow-up study in a memory clinic.

AIM: To determine characteristics of MCI that can predict whether patients will go on to develop AD or DLB. METHODS: Ninety-three patients diagnosed with MCI underwent neuropsychological and neuroimaging examinations, and were followed-up for a mean of 44.9±19.3months. They were divided into four MCI subtypes (amnestic/non-amnestic MCI, single/multiple domain) according to neuropsychological findings, and into three other MCI categories (AD-type PET, DLB-type PET, and unknown-type PET) based on (18)F-fluorodeoxyglucose PET findings. Patients who were eventually diagnosed with AD, DLB, other dementia, or remained MCI were analyzed in relation to the groups to which they had initially been allocated at the MCI stage. RESULTS: Clinical diagnosis after follow-up determined AD in 21 patients (22.6%), DLB in 12 patients (12.9%), other dementia in 2 patients (2.2%), and non-converter in 58 patients (62.3%). Amnestic single-domain MCI and AD-type PET tended to convert into AD. Amnestic multiple-domain MCI and DLB-type PET tended to convert into DLB. A few patients with AD-type PET later developed DLB, and some with DLB-type PET later developed AD. CONCLUSIONS: Predicting which type of dementia a person with MCI will later develop might be possible based on early assessment with clinical symptoms in conjunction with neuropsychological and (18)F-fluorodeoxyglucose PET findings.

Evaluation of titers of antibodies against peptides of subunits NR1 and NR2B of glutamate receptor by enzyme-linked immunosorbent assay in psychiatric patients with anti-thyroid antibodies.

BACKGROUND: Patients with anti-thyroid antibodies (ATAs) are reported to exhibit atypical psychiatric symptoms. We have been reported that psychiatric patients with ATAs (PPATs) have anti-N-methyl-Daspartate (NMDA) type glutamate receptor (NMDA-R) antibodies by western blot analysis. NMDA-R forms a tetramer with the subunit glutamate receptors (GluR) GluRζ1 (NR1) and GluRε2 (NR2B). However, the possible etiological role of anti-NR1 and anti-NR2B antibodies in PPATs remains unclear. METHODS: First, we evaluated titers of anti-NR1 and anti-NR2B antibodies in PPATs by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the relationships among titers of anti-NR1 and anti-NR2B antibodies. Finally, we investigated the relationship between anti-NMDAR antibodies and the psychiatric symptoms in the PPATs. RESULTS: There was a strong correlation between anti-NR1 antibodies and anti-NR2B antibodies in the CSF, and some correlation between these antibodies in the serum. High titers of anti-NR2B antibodies in the serum of PPATs contributed to development of hallucinations and high titers of anti-NR1 antibodies in the serum contributed to development of anxiety by logistic regression. CONCLUSION: High titers of anti-NR2B antibodies in the serum is a risk factor for hallucinations and high titers of anti-NR1 antibodies in the serum is a risk factor for anxiety in PPATs.

Early differential diagnosis between Alzheimer's disease and dementia with Lewy bodies: Comparison between (18)F-FDG PET and (123)I-IMP SPECT.

Both (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (123)I-iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) have been used for the differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Less information is available, however, regarding the differential diagnosis of mild cognitive impairment (MCI) due to AD and MCI due to DLB. We examined nine AD patients (AD group), nine DLB patients (DLB group), eight MCI due to AD patients (MCI-AD group), and nine MCI due to DLB patients (MCI-DLB group) with FDG PET and IMP SPECT using a well-characterized normal database and a stereotactic extraction estimation method. In the AD and DLB groups, receiver operating characteristic (ROC) analysis in the occipital regions showed significant accuracy of both FDG PET and IMP SPECT for the differential diagnosis. In the MCI-AD and MCI-DLB groups, ROC analysis showed significant accuracy of only FDG PET for the differential diagnosis. Both FDG PET and IMP SPECT would be useful for the differential diagnosis between AD and DLB. For the differential diagnosis of MCI-AD versus MCI-DLB, FDG PET would be more useful than IMP SPECT.