Gesture imitation performance in community-dwelling older people: assessment of a gesture imitation task in the screening and diagnosis of mild cognitive impairment and dementia.

BACKGROUND: Gesture imitation, a simple tool for assessing visuospatial/visuoconstructive functions, is reportedly useful for screening and diagnosing dementia. However, gesture imitation performance in healthy older adults is largely unknown, as are the factors associated with lower performance. To address these unknowns, we examined the gesture imitation performance of a large number of community-dwelling older adults aged ≥65 years in Arao City, Kumamoto Prefecture (southern Japan). METHODS: The examiner presented the participants with eight gesture patterns and considered it a success if they could imitate them within 10 s. The success rate of each gesture imitation was calculated for three diagnostic groups: cognitively normal (CN) (n = 1184), mild cognitive impairment (MCI) (n = 237), and dementia (n = 47). Next, we reorganised the original gesture imitation battery by combining six selected gestures with the following scoring method: if the participants successfully imitated the gestures, immediately or within 5 s, two points were assigned. If they succeeded within 5-10 s, one point was assigned. The sensitivity and specificity of the battery were investigated to detect the dementia and MCI groups. Factors associated with gesture imitation battery scores were examined. RESULTS: Except one complex gesture, the success rate of imitation in the CN group was high, approximately 90%. The sensitivity and specificity of the gesture imitation battery for discriminating between the dementia and CN groups and between the MCI and CN groups were 70%/88%, and 45%/75%, respectively. Ageing, male sex, and a diagnosis of dementia or MCI were associated with lower scores on the gesture imitation battery. CONCLUSION: Gesture imitation tasks alone may not be sufficient to detect MCI. However, by combining gestures with set time limits, gesture imitation tasks can be a low-burden and effective method for detecting dementia, even in community medicine, such as during health check-ups.

Comparison of caregiver burden between dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Caring for patients with dementia with Lewy bodies (DLB) would be more stressful for their caregivers than those with Alzheimer's disease (AD). In this study, we compared levels of caregiver burden and the possible influential factors on the caregiver burden between DLB and AD. METHODS: Ninety-three DLB patients and 500 AD patients were selected from the Kumamoto University Dementia Registry. Caregiver burden, neuropsychiatric symptoms, basic activities of daily living (BADL) and instrumental activities of daily living (IADL) were assessed by the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI), the Neuropsychiatric Inventory (NPI), the Physical Self-Maintenance Scale (PSMS), and the Lawton IADL scale, respectively. RESULTS: Despite the comparable Mini-Mental State Examination score, the J-ZBI score was significantly higher in the DLB group than the AD group (P = 0.012). A stepwise multiple regression analysis revealed that IADL score (ß = -0.23, P = 0.049), PSMS score (ß = -0.31, P = 0.010), disinhibition (ß = 0.22, P = 0.008), and anxiety (ß = 0.19, P = 0.027) were significantly associated with J-ZBI score in DLB. In AD, caregiver's relationship with patient (child) (ß = 0.104, P = 0.005), caregiver's gender (female) (ß = 0.106, P = 0.004), IADL score (ß = -0.237, P < 0.001), irritability (ß = 0.183, P < 0.001), apathy (ß = 0.132, P = 0.001), agitation (ß = 0.118, P = 0.007), and aberrant motor behaviour (ß = 0.107, P = 0.010) were associated with caregiver burden. CONCLUSIONS: Caring for DLB patients caused a higher degree of caregiver burden than AD patients in the same level of cognitive decline. The factors responsible for the caregiver's burden were different between DLB and AD. The caregiver burden for DLB patients was associated with the disability of basic ADL, IADL impairment, anxiety and disinhibition.

Late-manifestation of attention-deficit/hyperactivity disorder in older adults: an observational study.

BACKGROUND: The age of attention-deficit/hyperactivity disorder onset is usually during the first 12 years of life; however, there have been recent reports of late-onset attention-deficit/hyperactivity disorder. These reports have been limited to that of young adults, and details in older adults remain unknown. As such, we had previously presented the first case report of "very" late-onset attention-deficit/hyperactivity disorder, wherein the symptoms presented in senile age. In this observational study, we aimed to investigate the prevalence and clinical features of such attention-deficit/hyperactivity disorders in older adults visiting our dementia clinic. METHODS: Four hundred forty-six consecutive patients visiting our specialty outpatient clinic for dementia during the 2-year period from April 1, 2015 to March 31, 2017 were included in this study. First, the patients were examined for the presence or absence of dementia in our specialty outpatient clinic for dementia. Those not diagnosed with dementia were examined for the presence or absence of attention-deficit/hyperactivity disorder in our specialty outpatient clinic for developmental disorders. Finally, these patients who were diagnosed with attention-deficit/hyperactivity disorder were investigated in detail to clarify their clinical characteristics. RESULTS: Of 446 patients (246 women and 200 men), 7 patients were finally diagnosed with attention-deficit/hyperactivity disorder. Although these 7 patients were initially suspected to have Alzheimer's disease (considering their age, 6 of these 7 patients were suspected to have early onset Alzheimer's disease), it was found that these symptoms were due to attention-deficit/hyperactivity disorder. These patients had four characteristics in common: (1) they were significantly younger than the complete study population; (2) they predominantly showed inattention-related symptoms; (3) they showed latent manifestation; and (4) they experienced a stressful life event before manifestation. CONCLUSIONS: Our previous case report suggested that very late-onset attention-deficit/hyperactivity disorder patients could be incorrectly diagnosed with dementia. In this observational study, 1.6% of patients who were initially suspected of having dementia were actually diagnosed with attention-deficit/hyperactivity disorder. This study also showed that the "late-onset" described in our previous report would be better described as "late-manifestation." A clinician should consider late-manifestation of attention-deficit/hyperactivity disorder in the differential diagnosis when encountering dementia patients, especially early onset Alzheimer's disease.

Relationship between executive dysfunction and neuropsychiatric symptoms and impaired instrumental activities of daily living among patients with very mild Alzheimer's disease.

OBJECTIVES: Patients with Alzheimer's disease (AD) experience a gradual loss in their ability to perform instrumental activities of daily living (IADLs) from the early stage. A better understanding of the possible factors associated with IADL decline is important for the development of effective rehabilitation and support programs for patients with AD. Thus, we examined the relationships between comprehensive cognitive functions and neuropsychiatric symptoms and IADLs in patients with very mild AD. METHODS: In total, 230 outpatients with probable AD were recruited from the Memory Clinic at Kumamoto University Hospital between May 2007 and October 2016. All patients scored ≥21 points on the Mini-Mental State Examination at the first assessment. Relationships between the subdomains of the Lawton IADL scale and neuropsychological/neuropsychiatric tests were examined by multiple regression analysis. All analyses were performed separately in men and women. RESULTS: In female patients, scores on the Frontal Assessment Battery were significantly associated with telephone use ability, shopping, and ability to handle finances. Apathy scores in the Neuropsychiatric Inventory (NPI) were associated with telephone use ability, housekeeping, responsibility for own medications, and ability to handle finances. NPI agitation scores were associated with food preparation and housekeeping. Geriatric Depression Scale scores were associated with telephone use ability and ability to handle finances. In male patients, only NPI apathy scores were associated with telephone use ability. CONCLUSIONS: These results suggest the importance of properly assessing executive function, depression, and apathy at interventions for impaired IADLs among female patients with very mild AD.

Late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of dementia: a case report.

BACKGROUND: Although adult attention-deficit/hyperactivity disorder has recently gained increased attention, few reports on attention-deficit/hyperactivity disorder in the pre-elderly or elderly have been published. Here, we present the case of a patient with attention-deficit/hyperactivity disorder who gradually developed dementia-like symptoms as she aged, which initially made her condition difficult to distinguish from early onset Alzheimer's disease. This report illustrates that some types of attention-deficit/hyperactivity disorder may be misdiagnosed as dementia. CASE PRESENTATION: The patient was a 58-year-old woman. Although she presented with a tendency for inattentiveness and forgetfulness since childhood, she did not have a history of psychiatric disorders prior to consultation. Around the age of 52 years, her inattentiveness and forgetfulness gradually progressed, and at 57 years of age, she became inattentive and forgetful that it interfered with her work and daily life. For example, she forgot meetings with important clients and transferred money to the wrong bank account; these failures resulted in poor management of her company. At home, she experienced increasing difficulties with remembering prior commitments with her family and misplacing items, which her family members noticed. With the encouragement of her family and employees, who worried that she was suffering from dementia, she visited our memory clinic, whereby she was suspected of having early onset Alzheimer's disease. However, neuropsychological tests and brain imaging evaluations did not reveal any significant abnormalities. After dismissing various possible diagnoses, including dementia, other organic diseases, mood disorders, and delirium, we diagnosed her with attention-deficit/hyperactivity disorder. Treatment with 18 mg of methylphenidate was initiated, and significant improvements in her symptoms were observed within a few days; for example, she stopped losing her things, was able to concentrate for long durations, and could complete more tasks than she could before treatment. Since initiating treatment, she has returned to work and has been able to perform her daily activities without difficulty. CONCLUSIONS: This case supports that some patients with late-onset attention-deficit/hyperactivity disorder may gradually develop dementia-like symptoms during the pre-elderly and elderly stages of life. Therefore, clinicians should consider late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of some types of dementias.

Delusional parasitosis in dementia with Lewy bodies: a case report.

BACKGROUND: Dementia with Lewy bodies (DLB) is characterized by fluctuating cognitive impairments, recurrent visual hallucinations, the motor symptoms of parkinsonism and REM sleep behavior disorder. Various neuropsychiatric symptoms including hallucination and delusions occur frequently; however, delusional parasitosis is rare in DLB. Here, we report a case of DLB patient with delusional parasitosis. CASE PRESENTATION: The patient was an 89-year-old woman. At the age of 88, she began to complain her oral cenesthopathy, and developed cognitive decline, delusional parasitosis and parkinsonism. As a result of examination, she was diagnosed as DLB and treated with combination of donepezil 5 mg/day and aripiprazole 1.5 mg/day, and her complaint was disappeared. CONCLUSIONS: Further studies are needed to investigate the association between delusional parasitosis and underlying pathophysiology of DLB, and the utility of antipsychotics for delusional parasitosis in DLB has to be examined through more cases.

Emergence of artistic talent in progressive nonfluent aphasia: a case report.

Some patients with frontotemporal lobar degeneration have developed artistic skills after the onset mainly in painting and music. Most of these cases have semantic dementia (SD), one of the frontotemporal lobar degeneration subtypes. In previously reported cases, the paintings made by patients with SD were usually hyper realistic, without a significant symbolic or abstract component. Here, we report on a patient with progressive nonfluent aphasia (PNFA), another frontotemporal lobar degeneration subtype, who started making creative bamboo crafts after PNFA onset. His techniques were completely his original; he devised the shapes of the crafts and made them without samples. His work did not become an obsessive preoccupation. The artistic style expressed by patients with PNFA differs from that expressed by patients with SD. Therefore, the underlying mechanisms for the emergence of artistic talent might differ between SD and PNFA.

Relationship between dementia severity and behavioural and psychological symptoms in early-onset Alzheimer's disease.

BACKGROUND: The features of behavioural and psychological symptoms of dementia (BPSD) are influenced by dementia stage. In early-onset Alzheimer's disease (EOAD), the association between BPSD and dementia stage remains unclear because of the difficulty of recruiting subjects with a wide range of disease severity. We used a combination of community-based and hospital-based approaches to investigate the relationship between dementia severity and BPSD in EOAD patients. METHODS: Sixty-three consecutive EOAD outpatients and 29 EOAD patients from a community-based survey were divided into three dementia severity groups according to the Clinical Dementia Rating scale (CDR): mild (CDR 0.5-1, n = 55), moderate (CDR 2, n = 17), and severe (CDR 3, n = 20). BPSD were rated using the Neuropsychiatric Inventory. RESULTS: Scores of the Neuropsychiatric Inventory subscales agitation, euphoria, apathy, disinhibition, irritability, and aberrant motor behaviour increased significantly with increased dementia severity. Hallucinations were greater in the moderate group than in the mild group. For delusions, depression, and anxiety, no significant differences were observed among the three severity groups. CONCLUSIONS: The pattern of apathy, agitation, disinhibition, irritability, and aberrant motor behaviour worsening with severity progression in EOAD is similar to the pattern in late-onset Alzheimer's disease. In contrast, hallucinations, depression, and anxiety showed different patterns in EOAD.

Distribution of D-3-aminoisobutyrate-pyruvate aminotransferase in the rat brain.

BACKGROUND: D-3-aminoisobutyrate, an intermediary product of thymine, is converted to 2-methyl-3-oxopropanoate using pyruvate as an amino acceptor by D-3-aminoisobutyrate-pyruvate aminotransferase (D-AIB AT; EC 2.6.1.40). A large amount of D-AIB AT is distributed in the kidney and liver; however, small amounts are found in the brain. Recently, D-AIB AT was reported to metabolize asymmetric dimethylarginine (ADMA) in vivo and was suggested to be an important enzyme for nitric oxide metabolism because ADMA is a competitive inhibitor for nitric oxide synthase. In this study, we examined the distribution of D-AIB AT in the rat brain further to understand its role. We measured D-AIB AT mRNA and protein expression using quantitative RT-PCR and Western blotting, and monitored its distribution using immunohistochemical staining. RESULTS: D-AIB AT was distributed throughout the brain, with high expression in the cortex and hippocampus. Immunohistochemical staining revealed that D-AIB AT was highly expressed in the retrosplenial cortex and in hippocampal neurons. CONCLUSION: Our results suggest that D-AIB AT is distributed in the examined- just the regions and may play an important role there.

Apathy correlates with prefrontal amyloid ß deposition in Alzheimer's disease.

OBJECTIVE: Neuropsychiatric symptoms affect many patients with Alzheimer's disease (AD). ((11)C)Pittsburgh Compound-B (PIB) positron emission tomography (PET) has enabled the in vivo visualisation of brain amyloid-ß (Aß) deposition. This study exploratively investigated the correlation between brain Aß deposition measured by ((11)C)PIB PET and neuropsychiatric symptoms in AD. METHODS: Participants were 28 patients (15 women, 13 men) with PIB-positive AD. Clinical assessments included Mini-Mental State Examination, Clinical Dementia Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All patients underwent three-dimensional T1-weighted MRI and ((11)C)PIB PET. The distribution volume ratio (DVR), an index of ((11)C)PIB retention and, thus, Aß deposition, was estimated voxel by voxel from ((11)C)PIB PET data with partial volume correction. Voxel-based correlation analysis was performed to assess the relationships between DVR and each NPI subscale. Additionally, voxel-based analysis of covariance (ANCOVA) of the DVR images was performed between Patients with AD with and without each neuropsychiatric symptom. Voxel-based morphometry analysis of MRI was also performed. RESULTS: Apathy subscale was correlated with ((11)C)PIB retention in the bilateral frontal and right anterior cingulate. ((11)C)PIB retention was greater in the bilateral frontal cortex of patients with AD with apathy than those of without apathy. Overlapping areas between the two analyses were the bilateral orbitofrontal gyrus and left superior frontal gyrus. Other NPI subscales were not correlated with ((11)C)PIB retention. Voxel-based morphometry analysis of MRI showed no significant cluster of correlation between grey matter volume and NPI subscales. CONCLUSIONS: This study revealed that prefrontal Aß deposition correlates with apathy.

Family history of frontotemporal lobar degeneration in Asia--an international multi-center research.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.

Comparison of the utility of everyday memory test and the Alzheimer's Disease Assessment Scale-Cognitive part for evaluation of mild cognitive impairment and very mild Alzheimer's disease.

AIM: The purpose of this study was to compare the utility of the Rivermead Behavioural Memory Test (RBMT) and the Alzheimer's Disease Assessment Scale-Cognitive part (ADAS-Cog) for the evaluation of mild cognitive impairment (MCI) or very mild Alzheimer's disease (AD). METHODS: The discriminative abilities of RBMT and ADAS-Cog were compared in the very early stage of AD or MCI patients. Furthermore, we evaluated the difference in both RBMT score and ADAS-Cog score between different severities. RESULTS: Evident superiority in the false negative rate was observed in RBMT over ADAS-Cog in MCI or very mild AD. In addition, 86.7% of the subjects overlooked by ADAS-Cog were correctly detected by RBMT profile score. However, the RBMT score falls in the very early stages and the range of the RBMT score is rather narrow. As a result, it is difficult to evaluate status and follow the progression in severer cases. In contrast to RBMT, the ADAS-Cog score has a wide range and can evaluate and follow the severity in more severe cases. CONCLUSION: RBMT is more useful than ADAS-Cog in evaluating patients with MCI or very mild AD.

[A case report of early-onset Alzheimer's disease with multiple psychotic symptoms, finally diagnosed as APPV717I mutation by genetic testing].

It is difficult to confirm a diagnosis of early-onset Alzheimer's disease (EOAD) because patients sometimes have non-specific cortical features, such as psychiatric symptoms, executive functional impairment, and pyramidal symptoms, along with typical symptoms, such as recent memory impairment and disorientation. We encountered a patient with multiple psychotic symptoms, finally diagnosed with EOAD on genetic testing. A right-handed sixty-year-old man, whose mother was suspected of having dementia, developed memory impairment at the age of fifty, disorientation at the age of fifty-six, and both visual hallucination and dressing apraxia at the age of fifty-nine. After admission to a psychiatric hospital for treatment, his symptoms disappeared with antipsychotic medication. However, his ADL were declining and so he was referred to our university hospital. He had frontal lobe symptoms, pyramidal signs, and extrapyramidal signs with severe dementia. Neuropsychological examinations were not possible because of sedation. On brain MRI, he showed diffuse atrophy of the cerebral cortex and hippocampus. HMPO-SPECT showed hypoperfusion of cerebral cortices diffusely. We decided to perform genetic testing because he had both family and alcohol abuse histories. He showed EOAD with V717I mutation of the amyloid precursor protein gene. After the discontinuation of antipsychotics, excessive sedation and extrapyramidal signs disappeared. A dose of 10 mg of donepezil was effective to improve motivation and activity, and his mini mental examination score was calculable after recovery. The case supports usefulness of applying genetic testing for Alzheimer's disease to patients with early onset dementia, even when they do not have a family history.

Association of auditory Charles Bonnet syndrome with increased blood flow in the nondominant Brodmann area 22.

Aim: Auditory Charles Bonnet syndrome (aCBS) is characterized by musical hallucinations (MHs) that accompany acquired hearing impairments. This hallucination is the acoustic perception of music, sounds, or songs in the absence of an outside stimulus, and it may be associated with hyperactivity of the superior temporal lobes. Some studies have reported the possibility of improving MH with antiepileptics. To elucidate in detail the brain regions responsible for aCBS, we analyzed the regions that changed functionally after treatment. Methods: Before and after treatment with carbamazepine (four cases), clonazepam (one case), and a hearing aid (one case), cerebral perfusion single-photon emission computed tomography (SPECT) and the Auditory Hallucination Rating Scale (AHRS) were applied to six patients with hearing-loss-associated MHs. Results: Cerebral blood flow analysis using SPECT revealed hyperperfusion in Brodmann area (BA) 22-the posterior region of the superior temporal gyrus-in the nondominant hemisphere in all six patients in the pretreatment phase. After treatment, the hyperperfusion region improved in all patients. The area percentages with hyperperfusion in the nondominant BA22 were strongly positively correlated with the AHRS score. Conclusion: The results suggest that aCBS, which was treatable with antiepileptics or hearing aids, was involved in hyperexcitement in BA22, and that MH strength was correlated with degree of excitement.

Phenotypical difference of amyloid precursor protein (APP) V717L mutation in Japanese family.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD. CASE PRESENTATION: In this study, we report a 275341 G > C (Val717Leu) mutation in the APP gene in a Japanese family with early onset AD by genetic screening. This mutation has previously been detected in European families. In the Japanese family we screened, the age at onset of AD was 47.1 ± 3.1 years old (n = 9; range, 42-52). The symptoms in the affected members included psychiatric vulnerability and focal signs such as pyramidal signs, epileptic seizures, and myoclonic discharges. An MR imaging study showed relatively mild atrophic changes in the bilateral hippocampus and cerebral cortices in all affected members compared with their clinical presentations. CONCLUSION: We conclude that the clinical features of Alzheimer's disease can be different even when caused by the same mutation in the APP gene. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes.

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine.

BACKGROUND: This multicentre open-label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies. METHODS: Sixty-three dementia with Lewy bodies patients with probable BPSD (M:W, 30:33; mean age, 78.2±5.8 years) were enrolled and treated with YKS for 4 weeks. RESULTS: Significant improvements in Neuropsychiatric Inventory scores (mean decrease, 12.5 points; P<0.001) and Zarit Burden Interview-Japanese edition tests (mean decrease, 3.6 points; P=0.024) were observed. In patients who consented to an assessment after 2 weeks of treatment, a time-dependent significant improvement was observed in the Neuropsychiatric Inventory score (n=23; mean decrease, 14.4; P<0.001), each subscale, including delusions and hallucinations, the Zarit Burden Interview-Japanese edition (n=22; mean decrease, 8.2; P<0.01) and the behavioural pathology in Alzheimer's disease insomnia subscale. The Mini-Mental State Examination and the Disability Assessment for Dementia (DAD) showed no significant change. Adverse events were observed in 11 (18%) patients. Three patients (5%) discontinued YKS due to adverse reactions, namely, spasticity and exacerbation of BPSD, edema, and nausea. Hypokalaemia (<3.5 mEq/L) was present in four patients (6%) at the study endpoint. Worsening of extrapyramidal symptoms was not observed. CONCLUSION: YKS improved BPSD in dementia with Lewy bodies patients and caregiver burden scores without deterioration in cognitive function. YKS is useful for the treatment of delusions and hallucinations in BPSD.

A case report: Clozapine-induced leukopenia and neutropenia after mRNA COVID-19 vaccination.

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia and is known to cause serious side effects, such as leukopenia and neutropenia. We encountered the case of a 44-year-old female patient with a good response to clozapine, who experienced inflammatory reaction and cytopenia after coronavirus disease 2019 (COVID-19) vaccination. Soon after clozapine discontinuation, the inflammatory reaction resolved, and cell counts recovered. There are only a few reports on the interaction between clozapine and COVID-19 vaccine. Our findings suggest that caution is required when a patient who is receiving clozapine scheduled for COVID-19 vaccination, owing to the possibility of cytopenia. Moreover, blood tests and the measurement of clozapine concentration should be performed before and after the inoculation to ensure patient safety.

Brain structural alterations and clinical features of cognitive frailty in Japanese community-dwelling older adults: the Arao study (JPSC-AD).

Cognitive frailty (CF) is a clinical condition defined by the presence of both mild cognitive impairment (MCI) and physical frailty (PF). Elderly with CF are at greater risk of dementia than those with MCI or PF alone, but there are few known clinical or neuroimaging features to reliably distinguish CF from PF or MCI. We therefore conducted a population-based cross-sectional study of community elderly combining physical, cognitive, neuropsychiatric, and multisequence magnetic resonance imaging (MRI) evaluations. The MRI evaluation parameters included white matter (WM) lesion volumes, perivascular and deep subcortical WM lesion grades, lacunar infarct prevalence, microbleed number, and regional medial temporal lobe (MTL) volumes. Participants were divided into 4 groups according to the presence or absence of MCI and PF-(1) no MCI, PF (n = 27); (2) no PF, MCI (n = 119); (3) CF (MCI + PF) (n = 21), (4) normal controls (n = 716). Unique features of CF included shorter one-leg standing time; severe depressive symptoms; and MRI signs of significantly more WM lesions, lacunar infarcts, small-vessel disease lesions, microbleeds, and reduced MTL volumes. These unique deficits suggest that interventions for CF prevention and treatment should focus on motor skills, depressive symptoms, and vascular disease risk factor control.