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We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer’s disease (AD) using biomarkers.
Retrospective cross-sectional study.
Neuropsychology clinic of Osaka University Hospital in Japan.
Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP−AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI−P+AD) participants.
Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics.
Those in both VLOSLP−AD and +AD groups scored higher than those in aMCI−P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP−AD participants scoring significantly higher than aMCI−P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP−AD and +AD participants. Four VLOSLP−AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP−AD patients and five VLOSLP+AD patients.
Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.
To clarify the characteristic of impaired and unimpaired Instrumental Activities of daily living (IADL) processes with the severity of cognitive impairment in community-dwelling older adults with Alzheimer’s disease (AD) using the Process Analysis of Daily Activity for Dementia (PADA-D).
13 medical and care centers in Japan.
115 community-dwelling older adults with AD.
The severity of cognitive impairment was classified by Mini-Mental State Examination (20 ≥ mild group, 20 < moderate group ≥ 10, 10 < severe group), and IADL scores and eight IADL items in PADA-D were compared among three groups after adjusting for covariates. Rate of five feasible processes included in each IADL of PADA-D was compared.
IADL score showed a decrease in independence with the severity of AD except for Use modes of transportation and Managing finances, which was especially pronounced in Shopping (F = 25.58), Ability to use the telephone (F = 16.75), and Managing medication (F = 13.1). However, when the PADA-D was examined by process, some processes that were impaired and unimpaired with the severity of cognitive impairment were clear. For example, Plan a meal was impaired (ES = 0.29) with the severity, but Prepare the food was not in Cooking performance.
We suggested that detailed process analysis in IADLs can clarify the characteristic of processes that are impaired and unimpaired with the severity of cognitive impairment in older adults with AD living in the community. Our findings may be useful for rehabilitation and care in IADL to continue living at home.
Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia after Alzheimer’s disease. In some patients with DLB, relatively rare delusions are known to emerge, such as Othello syndrome, delusional parasitosis and delusion of duplication. Erotomania, also known as de Clerambault’s syndrome, is characterized by the delusion that a person has fallen in love with the patient. It occasionally appears secondary to psychiatric disorders and organic brain diseases. However, there have been no reports on cases secondary to patients with DLB.
The patient was an 83-year-old woman who lived alone. Mild cognitive impairment appeared at the age of 82 years. Soon after, she had the delusional conviction that her family doctor was in love with her. Her symptoms, such as gradually progressive cognitive impairment, cognitive fluctuations, and parkinsonism, indicated DLB. Although small doses of quetiapine, brexpiprazole and risperidone were prescribed for the treatment of the delusion, each of them was discontinued soon because of the adverse reactions. Finally, the delusion was successfully treated with a small dose of blonanserin without sever side effects.
Discussions and Conclusions:
This case report suggests the possibility of de Clerambault’s syndrome during the early stages of DLB. Recently, psychiatric-onset DLB has increasingly gained attention in recent years. Further accumulation of knowledge about delusions in patients with DLB for an early diagnosis.
To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH).
Osaka University Hospital.
Patients with possible iNPH underwent a CSF tap test.
Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients.
We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline.
A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.
Animal eggs are generally encased in one or more extra-cellular coats that protect the egg from biological, chemical and mechanical hazards. These coats contain some essential molecules for sperm to fertilise an appropriate egg, such as the specific ligand for sperm binding and the specific signal for induction of the acrosome reaction. In starfish, the outermost egg coat is a relatively thick gelatinous layer called the jelly coat. When starfish sperm encounter the jelly coat of homologous eggs, they undergo the acrosome reaction within a second or less (Dale et al., 1981; Ikadai & Hoshi, 1981; Sase et al., 1995). We have thus searched the jelly coat for the signal molecule(s) that triggers the acrosome reaction in the starfish, Asterias amurensis. It is known that three components in the jelly coat, namely acrosome reaction-inducing substance (ARIS), Co-ARIS and asterosap, act in concert on homologous spermatozoa to elicit the acrosome reaction immediately and efficiently (Hoshi et al., 1994,1999).
ARIS alone induces the acrosome reaction only in high calcium or high pH seawater. In normal seawater, besides ARIS, either Co-ARIS or asterosap is required for the induction. Without ARIS, no combination of Co-ARIS and asterosap can induce the acrosome reaction in normal, high calcium or high pH seawater. A mixture of ARIS and Co-ARIS increases the intracellular Ca2+ level, whereas asterosap increases the intra-cellular pH (Matsui et al., 1986a, b; Nishigaki et al., 1996). These events are prerequisites for the induction of the acrosome reaction. Indeed, the triad of ARIS, CoARIS and asterosap provides the best conditions for the induction of the acrosome reaction in normal sea-water (Hoshi et al., 1994, 1999).
Caregiver burden (CB) of Alzheimer's disease (AD) in Taiwan is becoming an urgent social issue as well as that in Japan. The comparison of CB may explain how caregiver feels burden in each country.
The participants were 343 outpatients with AD and their caregivers of Japan (n = 230) and Taiwan (n = 113). We assessed the CB using the Japanese and Chinese version of Zarit Caregiver Burden Interview (ZBI). The initial analysis was an exploratory factor analysis for each group to confirm the factor structure of ZBI. Then, the multiple-group structural equation modeling (MG-SEM) was used to assess the measurement invariance of ZBI such as configural, metric, and scalar invariances. Lastly, we compared the latent factor means of the ZBI between Japan and Taiwan.
In both groups, the confirmatory factor analysis extracted 3 factors which were labeled “Impact on caregiver's life”, “Embarrassed/anger”, and “Dependency”. The MG-SEM indicated an acceptable model fit, and established the partial scalar measurement invariance (comparative fit index (CFI) = 0.901, root mean square error of approximation (RMSEA) = 0.066). When we compared the latent factor means, the score of “Impact on caregiver's life” in Taiwanese caregivers was significantly higher than that in Japanese (p = 0.001). However, “Dependency” in Taiwanese caregivers was lower than that in Japanese (p < 0.001).
Partial measurement invariance allowed comparing the latent factor mean across two countries. The results of comparisons suggested that there may be differences in the way of feeling CB between Japan and Taiwan.
Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent.
Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups.
Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group.
These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake.
Previous studies in western countries have shown that about 30%–50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort.
Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient.
Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA.
In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.
Background: Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia. It is frequently difficult to differentiate DLB from Alzheimer's disease (AD) and other types of dementia. This study examined the usefulness of monitoring sleep talking for the diagnosis of DLB.
Methods: A total of 317 patients with dementia were selected from a consecutive series at the Dementia Clinic of Kumamoto University Hospital. Diagnostic categories consisted of probable DLB (n = 55), probable AD (n = 191), frontotemporal lobar degeneration (FTLD) (n = 16), vascular dementia (VaD) (n = 18), and other/unspecified dementia (n = 37). We evaluated sleep talking in all dementia patients and normal elderly subjects (n = 32) using an originally designed sleep talking questionnaire.
Results: Sleep talking occurred most frequently in the DLB group (61.8%), followed by the VaD group (33.3%), other/unspecified dementia group (27.0%), AD group (18.8%), FTLD group (12.5%), and normal elderly subjects group (6.3%). The prevalence of sleep talking in the DLB group was significantly higher than in other groups, except in the VaD group. The sleep talking yielded high specificity (81.2%) and some sensitivity (61.8%) for the differential diagnosis of DLB from AD. Furthermore, loud sleep talking may improve the specificity (96.9%). For the differentiation of DLB from all other dementia types, the specificity of sleep talking and loud sleep talking was also high (79.4% and 95.8% respectively).
Conclusions: Assessing sleep talking, especially the volume of sleep talking, may be useful in the clinical discrimination of DLB from not only AD but also from all other types of dementia.
Background: Memory impairment has been proposed as the most common early sign of Alzheimer's disease (AD). The aims of this work were to evaluate the risk of progression from mild memory impairment/no dementia (MMI/ND) to clinically diagnosable AD in a community-based prospective cohort and to establish the risk factors for progression from MMI/ND to AD in the elderly.
Methods: Elderly subjects aged over 65 years were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit on objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. A total of 104 MMI/ND subjects selected from 1242 community-dwellers were followed longitudinally for five years.
Results: During the five-year follow-up, 11 (10.6%) subjects were diagnosed with AD, five (4.8%) with vascular dementia (VaD), and six (5.8%) with dementia of other etiology. Logistic regression analysis revealed that diabetes mellitus (DM) and a family history of dementia (within third-degree relatives) were positively associated with progression to AD, while no factor was significantly associated with progression to VaD or all types of dementia.
Conclusions: DM and a family history of dementia were significant risk factors for progression from MMI/ND to clinically diagnosable AD in the elderly in a Japanese community.
Background: Alzheimer's drugs are believed to have limited availability and to be unaffordable in low- and middle-income countries compared to high-income countries. The price, availability and affordability of Alzheimer's drugs have not been reported before.
Methods: During 2007 an international survey was conducted in 21 countries in six continents (Argentina, Australia, Brazil, the Dominican Republic, France, India, Japan, Macedonia, Mexico, New Zealand, Nigeria, the Philippines, Portugal, Serbia, South Korea, Switzerland, Taiwan, Thailand, Uganda, the U.K. and the U.S.A.). Prices of Alzheimer's drugs were compared using the affordability index (the total number of units purchasable with one's daily income) derived from purchasing power parity (PPP) converted prices as well as raw prices.
Results: Donepezil is available in all 21 countries, whereas the newer drugs are less available. A 5 mg tablet of branded originator donepezil costs just US$0.26 in India and US$0.31 in Mexico, whereas it costs US$6.64 in the U.S.A. Pricing conditions of rivastigmine, galantamine and memantine appear to be similar to that of donepezil. The cheapest branded originators are from India and Mexico. However, in terms of PPP, Alzheimer's drugs in other low- and middle-income countries are much more expensive than in high-income countries. Most people in low- and middle-income countries cannot afford Alzheimer's drugs.
Conclusions: Alzheimer's drugs, albeit available, are often unaffordable for those who need them most. It is hoped that equitable differential pricing will be applied to Alzheimer's drugs.
Background: Eating problems occur frequently in patients with dementia, and almost half of all patients with Parkinson's disease have such problems. It has therefore been assumed that eating problems are also common in patients with dementia with Lewy bodies (DLB). However, few systematic studies have investigated eating problems in DLB patients. The aim of this study was to clarify the frequency and characteristics of eating problems in patients with DLB.
Methods: We examined 29 consecutive patients with DLB and 33 with Alzheimer's disease (AD) in terms of age, sex, education, Mini-mental State Examination, clinical dementia rating (CDR), neuropsychiatric inventory (NPI), Unified Parkinson disease rating scale (UPDRS), fluctuations in cognition, and usage of neuroleptic drugs / antiparkinsonian drugs. We employed a comprehensive questionnaire comprising 40 items and compared the scores between the two groups.
Results: DLB patients showed significantly higher scores than AD patients for “difficulty in swallowing foods,” “difficulty in swallowing liquids,” “coughing or choking when swallowing,” “taking a long time to swallow,” “suffering from sputum,” “loss of appetite,” “need watching or help,” and “constipation”. Only the UPDRS score significantly affected the scores for “difficulty in swallowing foods,” “taking a long time to swallow” and “needs watching or help” score, whereas only the NPI score affected the score for “loss of appetite.” The scores for UPDRS, NPI and CDR significantly affected the scores for “difficulty in swallowing liquids.” No significant independent variables affected the scores for “coughing or choking when swallowing,” “suffering from sputum” and “constipation.”
Conclusion: Although DLB patients show many eating problems, the causes of each problem vary, and the severity of dementia or Parkinsonism is not the only determinant.
The purpose of this study was to determine the effectiveness of muscle-release surgery for children with cerebral palsy (CP) using longitudinal and stratified analysis. Twenty-five children with CP (15 females, 10 males; age range 4 to 16 years; mean age 8 years 2 months, SD 3 years 2 months) were selected from five treatment centres in Japan. Twenty-two children had spastic diplegia, two had spastic quadriplegia, and one had athetospastic quadriplegia. Motor function for each child was assessed using the Gross Motor Function Measure (GMFM). Assessment was conducted on eight separate occasions: 1 month and 1 week before surgery, and 1, 2, 4, 6, 9, and 12 months after surgery. Participants' motor function before surgery was classified using the Gross Motor Function Classification System (GMFCS). Six children were classified at level I, three at level II, six at level III, and 10 at level IV. A significant difference was found after surgery in the GMFCS levels III and IV groups (p<0.05). Improvement in GMFM scores between 1 week before surgery and 12 months after surgery were 1, 5, 8.5, and 8.5 for GMFCS levels I to IV respectively. Results indicate that this treatment is advantageous for improving motor function in children within GMFCS levels III and IV.
Emotional memory is a special category of memory for events arousing strong emotions. To investigate the effects of emotional involvement on memory retention in individuals with Alzheimer's disease we studied peoples' memories of distressing experiences during a devastating earthquake.
Fifty-one subjects with probable Alzheimer's disease who experienced the Kobe earthquake at home in the greater Kobe area were studied. Memories of the earthquake were assessed 6 and 10 weeks after the disaster in semi-structured interviews, and were compared with memories of a magnetic resonance imaging (MRI) examination given after the earthquake.
Forty-four (86.3%) of the subjects remembered the earthquake and 16 (31.4%) of subjects remembered the MRI experience. Factual content of the earthquake was lost in most of the subjects.
Fear reinforces memory retention of an episode in subjects with Alzheimer's disease but does not enhance retention of its context, despite repeated exposure to the information.
A new procedure for aspiration which closes the larynx at the level of the false cords is reported. This method is not harmful to the vocal folds and maintains arytenoid movement, thus preserving phonatory function. With the advance of the operative technique for aspiration and swallowing rehabilitation, patients who have recovered from aspiration can be helped. Our procedure can be recommended for such cases.
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