Correlation between cerebral blood flow and olfactory function in mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: Olfactory dysfunction is common in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We sought to elucidate brain regions associated with olfactory dysfunction in patients with MCI and early AD by using 123I-IMP-SPECT to detect regional cerebral blood flow (CBF). METHODS: We included 218 patients diagnosed with AD or MCI, who underwent a comprehensive battery of neuropsychiatric and neuropsychological tests, Alzheimer's Disease Assessment Scale-Cognitive Part (ADAS-Cog), and forward- and backward-digit span. Olfactory function was assessed using T&T olfactometry of five odors; patients stated whether they experienced any smell (detection test) and identified the odor (identification test). The association between single-photon emission computerized tomography based regional CBF and olfactory function was examined by voxel-by-voxel multiple regression analysis, considering sex, age, and education as covariate parameters. RESULTS: Of the 218 patients, 78 had mildly impaired olfactory detection and 15 had olfactory detection loss; additionally, 213 had mild olfactory identification impairment. The odor detection score correlated significantly with the ADAS-Cog word recall score (r = 0.193, p = 0.004). The odor identification score correlated significantly with the ADAS memory (r = 0.408, p < 0.001) and ADAS orientation (r = 0.292, p < 0.001) scores. The odor identification score correlated negatively with CBF in the left temporal pole, entorhinal area, and bilateral frontal poles (p < 0.001). CONCLUSION: Olfactory identification dysfunction in patients with MCI and AD is attributable to reduced CBF of the left temporal pole, entorhinal area, and bilateral frontal pole.

Dual genetic absence of STAT6 and IL-10 does not abrogate anti-hyperglycemic effects of Schistosoma mansoni in streptozotocin-treated diabetic mice.

Schistosoma mansoni (Sm) is known to exert protective effects against various allergic and autoimmune disorders. It has been reported that this parasite protects NOD mice from spontaneous type 1 diabetes (T1D) and ameliorates streptozotocin (STZ)-induced T1D in wild-type mice. Here, we tried to clarify the anti-diabetic mechanisms of Sm in the latter model. Sm infection partially prevented the degradation of pancreatic islets and hyperglycemia in multiple low-dose (MLD) STZ-treated mice. Neither Treg cell depletion nor genetic absences of IL-10 and/or STAT6 abrogated the anti-hyperglycemic effects of Sm. Among M2 macrophage markers, Arg-1 and Ym1, but not Retnla, remained up-regulated in the pancreatic lymph nodes and in the spleens of STAT6/IL-10 double deficient (DKO) mice. Collectively, it is suggested that Sm exerts anti-diabetic effects on this experimental T1D model via Treg/IL-4/IL-13/IL-10-independent mechanisms. Augmented expressions of Arg-1 and Ym1 in the lymphoid organs adjacent to pancreas may be relevant to the anti-diabetic effects of Sm.

The creation and dissemination of downloadable information on dementia and driving from a social health perspective.

BACKGROUND: Driving cessation is a likely consequence of progressive dementia. Patients and families can benefit from support through this transition, both to safeguard the patient and public and to help preserve healthy social activity of the patient. METHODS: To provide appropriate supportive information, we developed a 35-page manual ('Supporting family caregivers of older drivers with dementia') available as a free download from our department website. We then informed municipal governments of its availability, tracked website access metrics, and followed up 7 months later with a postal survey to the heads of each municipal government's department of welfare for older citizens. RESULTS: From February to September 2010, the manual was accessed 33 494 times. Of the 1750 municipalities sent surveys, we received 1067 responses (61%). The responses showed that 943 professionals (94.6%) were able to obtain information they needed from the manual, 247 (23%) had used the manual to help residents during the 7 months, and 89% of those who used the manual used it to provide relevant advice to family caregivers. The responses also showed that significantly more use occurred in towns and villages as opposed to cities, consistent with the limited public transportation options in smaller municipalities (P = 0.002). CONCLUSIONS: We anticipate that use of this manual will raise general awareness of this social health issue and facilitate collaborations to provide more social support for those with dementia and their family members.

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid.

A novel method for the synthesis of trisubstituted oxazoles via a one-pot oxazole synthesis/Suzuki-Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki-Miyaura coupling with boronic acids provided the corresponding 2,4,5-trisubstituted oxazoles in good yields.

Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

BACKGROUND: Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). METHODS: The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. RESULTS: Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P < 0.01). CONCLUSIONS: Patients with FTLD were more likely to show dangerous driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage.

Improvement in gait velocity variability after cerebrospinal fluid elimination and its relationship to clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. METHODS: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG-CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini-Mental State Examination and the Frontal Assessment Battery. RESULTS: The TUG, TUG-CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre-CSF elimination results showed that the TUG-CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini-Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini-Mental State Examination results were significant predictors of the TUG-CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG-CV. CONCLUSIONS: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693-699.

Predictors of probable attention deficit hyperactivity disorder in elderly patients with mild cognitive impairment visiting a memory clinic.

Aim: Characteristics of attention deficit hyperactivity disorder (ADHD) that persist into old age are often confused with symptoms of mild cognitive impairment (MCI), and the actual rate of probable ADHD in people with MCI is unknown. This study estimated the proportion of MCI patients with probable ADHD and investigated the factors to identify MCI patients with probable ADHD. Methods: We recruited 36 elderly patients (11 males, 25 females, mean age 72.4 ± 7.6 years) who met the MCI criteria. The MCI patients were classified as those with [MCI/ADHD (+)] and without [MCI/ADHD (-)] probable ADHD, according to the Wender Utah Rating Scale scores. The autism features, inattention, and hyperactivity features during childhood and current periods, estimated intelligence quotient, and demographic data were compared between the groups. Multiple logistic regression analysis was performed to identify factors of MCI/ADHD (+) patients. Results: Nine (25.0%) and 27 patients were added into the MCI/ADHD (+) and MCI/ADHD (-) groups, respectively. The MCI/ADHD (+) group mostly comprised men, those who visited the clinic at a younger age, had more years of schooling, and had strong autism spectrum disorder tendencies. Multiple logistic regression analysis indicated male sex and current hyperactivity as significant predictors of probable ADHD in MCI patients. Conclusion: A quarter of the patients with MCI had probable ADHD. Male sex and hyperactivity at the time of MCI diagnosis might help in predicting probable ADHD in MCI patients. However, these results were obtained from a single-center, small-case study and should be confirmed via longitudinal studies with a large number of cases.

Influences of donepezil on cardiovascular system--possible therapeutic benefits for heart failure--donepezil cardiac test registry (DOCTER) study.

To study prospectively influences of donepezil, an acetylcholinesterase inhibitor against Alzheimer disease, on cardiovascular system, we evaluated cardiovascular changes occurring during new initialized treatment with donepezil in 49 dementia patients over 6 months. No patient suffered from cardiovascular events. In clinical changes between baseline and the first evaluation after donepezil treatment, heart rate and plasma brain natriuretic peptide (BNP) levels as a marker for heart failure did not change (BNP: 59.62 ± 62.71 pg/mL at baseline to 53.18 ± 42.34 pg/mL at first evaluation; P = 0.262). We further examined plasma BNP levels in 2 groups into which the patients were divided at baseline according to the cut-off plasma BNP level of 60 pg/mL. In patients with high level of BNP, the BNP levels decreased after administration of donepezil (116.39 ± 76.58 pg/mL at baseline to 82.24 ± 46.64 pg/mL at first evaluation; P = 0.011) with the tendency to be reduced in the follow-up period. BNP did not change in patients with low level of BNP. Donepezil seemed to be safe in patients with dementia without symptomatic heart disease and significantly decreased plasma BNP levels in patients with subclinical chronic heart failure.

Association of right precuneus compression with apathy in idiopathic normal pressure hydrocephalus: a pilot study.

Apathy is frequently observed in idiopathic normal pressure hydrocephalus (iNPH) and worsens cognitive impairment and gait disturbance. In this study, we evaluated the regions associated with apathy in iNPH using statistical imaging analysis on the whole brain, both in terms of cerebral blood flow and gray matter volume. Twenty-seven patients with iNPH were assigned to two groups based on their scores on the neuropsychiatric inventory items related to apathy; 18 patients were assigned to the group with apathy (iNPH + APA) and 9 to the group without apathy (iNPH - APA). The magnetic resonance images and cerebral blood flow single-photon emission computed tomography data of the two groups were compared using statistical parametric mapping 12. The regional gray matter volume of the right precuneus was significantly larger in the iNPH + APA group than in the iNPH - APA group, but the regional cerebral blood flow in any region of the brain was not significantly different between the two groups. These results suggested that the larger gray matter volume, which is thought to reflect gray matter compression, in the precuneus might be involved in apathy in iNPH.

Family psychoeducation for major depression: randomised controlled trial.

BACKGROUND: The value of family psychoeducation for schizophrenia has been well established, and indications for its use have recently expanded to include bipolar affective disorder. However, no study to date has adequately examined its use in depression. AIMS: To examine family psychoeducation in the maintenance treatment of depression and to investigate the influence of the family's expressed emotion (EE) on its effectiveness. METHOD: Of 103 patients diagnosed with major depression and their primary family members, 57 pairs provided written informed consent. The pairs were randomly allocated to the intervention (n = 25) or control (n = 32). One family in the intervention group and two in the control group withdrew their consent after randomisation. The intervention group underwent four psychoeducation sessions consisting of didactic lectures about depression and group problem-solving focusing on how to cope in high-EE situations. Patients did not attend these sessions. Patients in both the intervention and control groups received treatment as usual. The families' EE levels were evaluated through Five-Minute Speech Samples. The primary outcome was relapse. RESULTS: Time to relapse was statistically significantly longer in the psychoeducation group than in the control group (Kaplan-Meier survival analysis, P = 0.002). The relapse rates up to the 9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI 0.04-0.66; number needed to treat 2.4, 95% CI 1.6-4.9). In Cox proportional hazard analysis, baseline EE did not moderate the effectiveness of the intervention. CONCLUSIONS: Family psychoeducation is effective in the prevention of relapse in adult patients with major depression.

Clinical profiles of people with dementia exhibiting with neuropsychiatric symptoms admitted to mental hospitals: A multicenter prospective survey in Japan.

AIMS: Patients with severe behavioral and psychological symptoms of dementia (BPSD) are often admitted to mental hospitals, while, inpatient care could also lead to prolonged hospital stay. The present study aims to survey clinical profiles of patients who required inpatient treatment for BPSD, and then establish the criteria for introducing inpatient treatment through assessment by certified psychiatrists. METHODS: We performed a prospective survey about clinical characteristics of people with dementia who required treatment of BPSD at 12 mental medical institutions. All patients were assessed by certified psychiatrists to determine the optimal treatment settings: outpatient or inpatient. The multivariate logistic regression analysis was performed to specify factors contributed to the judgement of clinicians. Subsequently, the receiver operating characteristic curve analysis was conducted to explore a score derived from the Neuropsychiatric Inventory to divide patients into outpatient or inpatient groups. RESULTS: The present study included 386 patients, of which 242 were admitted to mental hospitals. BPSD were classified into four domains, and aggressive BPSD was significantly associated with assessment for inpatient treatment; the adjusted odds ratio was approximately 2 regardless of dementia severity. Furthermore, the composite score of agitation, irritability and aberrant behavior showed the highest area under the curve value (=0.706), which differentiated inpatients from outpatients with a sensitivity of 76% and a specificity of 54%. CONCLUSIONS: Aggressive BPSD was the risk factor for inpatient treatment. The composite score of the Neuropsychiatric Inventory subdomain-related aggressive BPSD could be a screening tool to introduce inpatient treatment for BPSD. Geriatr Gerontol Int 2021; 21: 825-829.

Correlation between regional brain volume and olfactory function in very mild amnestic patients.

BACKGROUND & AIMS: We aimed to determine neural correlates of olfactory detection and identification and analyze associations between cognitive function and olfactory identification or detection in very mild amnestic patients. METHODS: We recruited 70 patients with chief complaints of memory impairment diagnosed as amnestic mild cognitive impairment (MCI) or Alzheimer's disease (AD) with a clinical dementia rating of 0.5. Olfactory detection and identification were assessed using T&T olfactometry. A voxel-wise correlation analysis of gray matter volume and olfactometry scores was performed. We also analyzed correlations between neuropsychological results and olfactometry scores. RESULTS: A significant negative correlation was observed between detection scores and nucleus accumbens and left parahippocampal gyrus volumes and between identification scores and orbitofrontal, right frontal, and right anterior temporal cortex volumes (p < .001). No significant correlation existed between detection and cognitive assessment scores. Identification score was significantly correlated with the Alzheimer's Disease Assessment Scale-Cognitive Part word recall score (r = 0.305, p = .01). CONCLUSIONS: Olfactory detection and identification dysfunction were attributable to impairments in different regions in MCI and very early AD; the former was attributed to the olfactory circuit, while the latter to neocortices. The dysfunction of identification of olfactory information was associated with episodic memory in those patients.

Structural variation in the glycogen synthase kinase 3ß and brain-derived neurotrophic factor genes in Japanese patients with bipolar disorders.

BACKGROUND: Lithium is the first-line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3ß and brain-derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium. METHOD: Fifty patients with BDs and 50 healthy subjects (mean age 55.0 ± 15.0 years; M/F 19/31) participated. We examined structural variation of the GSK3ß and BDNF genes by real-time PCR. We examined the influence of structural variation of these genes on the therapeutic responses to lithium and the occurrence of antidepressant-emergent affective switch (AEAS). The efficacy of lithium was assessed using the Alda scale, and AEAS was evaluated using Young Mania Rating Scale. RESULTS: Although we examined structural variations within intron II and VII of the GSK3® gene and from the end of exon IV to intron IV and within exon IX of the BDNF gene, no structural variation was found in BDs. Whereas 5 of 50 patients exhibited three copies of the genomic region within exon IV of the BDNF gene, all healthy subjects had two copies. No difference in the therapeutic efficacy of lithium was found between patients with three and two copies. No difference in the occurrence of AEAS was found between the two groups. CONCLUSION: The amplification of the BDNF gene influenced neither the therapeutic responses to lithium nor the occurrence of AEAS.

Musical deficits and cortical thickness in people with schizophrenia.

Investigation of acquired amusia caused by brain damage suggested that cortical lesions of the right hemisphere contributed to musical deficits. We previously reported reduced musical ability in schizophrenia; these deficits were correlated with clinical manifestations such as cognitive dysfunction and negative symptoms. However, the neural substrate underlying the musical disability in schizophrenia remains unclear. We investigated the relationship between musical deficits and cortical thickness in patients with schizophrenia using structural MRI. We recruited 24 patients (13 males; age mean=45.9years old), and 22 controls (14 males, age mean=43.5years old). Musical ability was assessed with the Montreal Battery for Evaluation of Amusia (MBEA), cognitive function with the Brief Assessment of Cognition in Schizophrenia (BACS) and clinical features of illness with the Positive and Negative Syndrome Scale (PANSS). MRI Images were acquired and processed using FreeSurfer. Surface-based analysis showed that thinner cortex in left temporal and inferior frontal region was associated with lower musical ability in schizophrenia. In contrast, in controls thicker cortex in the left supramarginal region was correlated with lower musical ability. These results shed light on the clinical pathology underlying the associations of musical ability, cognitive dysfunction and negative symptoms in patients with schizophrenia.

Violation of Laws in Frontotemporal Dementia: A Multicenter Study in Japan.

Although violations of laws, such as shoplifting, are considered to be common in frontotemporal dementia (FTD) patients, there have been few studies on this subject and the frequencies and types of such violations have not been clarified. The objective of this study was to conduct a retrospective investigation of FTD patients in the psychiatry departments of multiple institutions to determine the types and frequencies of any law violations and compare them with those of AD patients. All patients were examined between January 2011 and December 2015 at the specialized dementia outpatient clinics of 10 facilities (5 psychiatry departments of university hospitals, 5 psychiatric hospitals). According to diagnostic criteria, 73 behavior variant FTD (bvFTD) patients, 84 semantic variant of primary progressive aphasia (svPPA) patients, and 255 age- and sex-matched AD subjects as the control group were selected. The findings revealed a higher rate of law violations in the bvFTD and svPPA patients before the initial consultation as compared to the AD group (bvFTD: 33%, svPPA: 21%, AD: 6%) and that many patients had been referred due to such violations. Laws had been broken 4 times or 5 or more times in several cases in the FTD group before the initial consultation. Regarding rates for different types of violation, in bvFTD subjects, the highest rate was for theft, followed by nuisance acts and hit and run. In svPPA, theft had the highest rate, followed by ignoring road signs. There was no gender difference in law violations but they were more frequent when the disease was severe at the initial consultation in the FTD group. As the rates of law violations after the initial consultation were lower than before it, interventions were considered to have been effective. These findings may be useful for future prevention as well as to the legal system.

Callosal Disconnection Syndrome Associated with Relapsing Polychondritis.

Relapsing polychondritis (RP) is a rare inflammatory disorder of the cartilagenous structures, and it sometimes involves the central nervous system. Encephalitis associated with RP causes a wide variety of symptoms according to the affected sites. We herein report the first case of 72-year-old right-handed man who developed acute meningoencephalitis associated with RP involving the corpus callous. After immunosuppressive therapy, his symptoms dramatically improved, but difficulty in performing bimanual movements with occasional diagonistic dyspraxia in his right hand remained. Because callosal signs are easily missed, especially in acute settings, it would be useful to know that RP can sometimes cause callosal disconnection syndrome.

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions.

BACKGROUND: Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test. METHODS: The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer's disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs. RESULTS: The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%. CONCLUSIONS: Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

[Dementia and driving: present status of drivers with dementia and response of their family's care in Japan].

As a result of the growing proportion of drivers aged 65 years and older, it is estimated that the number of elderly drivers with dementia is increasing in Japan. Since June 2002, if a driver is found to be "demented", his/her driving license shall be revoked in Japan. However, there are no consensus guidelines for demented drivers. Between September 1995 and September 2001, we evaluated 30 drivers with dementia (19 males and 11 females, mean age of 69.4 years) in out patients clinic of the Kochi Medical School Hospital and related hospitals. Clinical Diagnosis was Alzheimer's disease in 20, vascular dementia in 3, mixed type dementia in 2, frontotemporal lobar degeneration in 4, other type dementia in 1. We analyzed their driving behavior and family's attitude. Seventy-three point three percent of 30 drivers with dementia continued to drive after diagnosis. In follow-up periods, number of drivers continuing driving was decreased to 13 (43.3%), while six drivers (27.3%) had a traffic accident or violation. Our study suggests that several important medical and social factors should be considered for the management of drivers with dementia. A consensus medical guideline for demented drivers has to be established.

Relationship between Dementia Severity and Behavioral and Psychological Symptoms of Dementia in Dementia with Lewy Bodies and Alzheimer's Disease Patients.

BACKGROUND/AIMS: Behavioral and psychological symptoms of dementia (BPSD) are common in the clinical manifestation of dementia. Although most patients with dementia exhibit some BPSD during the course of the illness, the association of BPSD with the stage of dementia remains unclear. It was the aim of this study to evaluate the impact of severity of dementia on the expression of BPSD in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Ninety-seven patients with DLB and 393 patients with AD were recruited from 8 dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric Inventory (NPI). A relationship between BPSD and dementia stage classified by the Clinical Dementia Rating (CDR) in each type of dementia was assessed. RESULTS: No significant difference was seen in NPI total score across CDR staging in the DLB group. On the other hand, the NPI total score significantly increased with dementia stage in the AD group. CONCLUSION: The relationship of dementia stage with the expression of BPSD was different according to the type of dementia. BPSD and dementia stage were correlated in AD subjects, in whom psychiatric symptoms increase as the disease progresses, but not in DLB subjects.