[Examination of the effect of immunosuppressive therapy on acquired hemophilia A in elderly patients with bloodstream infections].

AIM: Acquired hemophilia A (AHA) is an acquired autoantibody (inhibitor) against blood coagulation factor VIII (FVIII) that significantly reduces FVIII activity and causes a bleeding tendency. Immune acquired coagulation factor deficiency. The peak age of onset is in the 70s. In Japan, which has an aging society, the number of reports has recently been increasing, and it should be noted that AHA is a bleeding disease that can occur in the elderly. Examined 5 cases of AHA that were experienced in our hospital. The FVIII inhibitor level, APTT, underlying disease, treatment history, and outcome were retrospectively examined using medical records. RESULTS: The age of onset was 76-93 years. At the time of diagnosis, the Hb (mg/dL) value was 6.1-10.3, the APTT was 75.6-203.2 seconds, the FVIII inhibitor value (BU/mL) was 18-686, and the platelet count was within the normal range in all cases. Bleeding control was possible using a bypass hemostatic agent in 4 patients. All patients underwent immunosuppressive therapy. Two patients were discharged alive and 3 patients died. The cause of death was infectious disease in all cases. The total prednisolone-equivalent dose of the deceased patients was 1,240-3,206 mg; one patient was treated with cyclophosphamide and was treated with dexamethasone. CONCLUSION: Long-term immunosuppressive therapy is expected to increase the risk of infection in elderly patients. The risk assessment of AHA treatment-related bloodstream infections is insufficient, and it will be necessary to accumulate data and consider appropriate assessments and countermeasures.

Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Although frailty is closely linked to dementia, particularly Alzheimer's disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty. METHODS: A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.7±6.3 years) who underwent both magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) were enrolled in this study. Frailty was determined in accordance with the Obu study Health Promotion for the Elderly. We compared numbers of small infarctions in the subcortical gray and white matter and severity of white matter abnormalities (periventricular hyperintensity [PVH] and deep white matter hyperintensity [DWMH]) on MRI, and regional cerebral blood flow (rCBF) changes on SPECT between AD with and without frailty. RESULTS: The prevalence of frailty was 43.4% in patients with AD. PVH and DWMH scores were significantly higher in AD with frailty compared to those without frailty. AD with frailty had a trend of decreased rCBF in the bilateral anterior cingulate gyrus, whereas those without frailty tend to have decreased rCBF in the left dominant parietal lobe and precuneus. CONCLUSION: Our MRI and SPECT imaging studies suggest different underlying pathophysiology in the brain between AD with frailty and without frailty.

Caregivers' education decreases depression symptoms and burden in caregivers of patients with dementia.

OBJECTIVE: To determine whether providing education to caregivers of patients with dementia decreases their depression symptoms and burden. METHODS: Eighty-three outpatients with dementia being treated at the Memory Clinic of Tokyo Medical University Hospital and their caregivers were enrolled. Forty-seven caregivers were enrolled in the caregivers' education (EDU) group and 36 were enrolled in the control (CTL) group. Caregivers were assessed for depression, burden, and quality of life (QoL). Patients were assessed for cognition, psychological symptoms, and QoL. Assessments were carried out at baseline and at 3 months (3M). Caregivers in the EDU group received lectures on symptoms and progression of dementia, management of symptoms, use of social resources etc. RESULTS: At 3M, prevalence of depression symptoms in the EDU group significantly decreased from 36% to 17%, whereas it significantly increased from 22% to 50% in the CTL group. Depression and burden were significantly improved at 3M in the EDU group, whereas they significantly worsened in the CTL group. Psychological symptoms showed a lower tendency at 3M for the EDU group. No significant changes in QoL of caregivers and patients were found in either group. CONCLUSIONS: Providing education to caregivers of patients with dementia improves their depression symptoms and sense of burden, and tends to improve the behaviour and psychological symptoms of dementia in the patients. Providing education to caregivers of dementia patients may hence result in beneficial effects for both the patients and their caregivers, and should be widely used in dementia care.

Comparison of diagnostic utility of semi-quantitative analysis for DAT-SPECT for distinguishing DLB from AD.

PURPOSE: It is widely known that there is low striatal 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). However, a consistent quantitative evaluation method for DAT-SPECT has not yet been established. There are two semi-quantitative software packages for DAT-SPECT available in Japan, namely, DaTView and DaTQUANT. The aim of this study was to identify which of these is superior for distinguishing DLB from AD. Moreover, we aimed to identify which region of the striatum is more suitable for distinguishing DLB from AD. METHODS: Patients with Alzheimer's disease (AD) (n=95) and patients with DLB (n=133) who underwent DAT-SPECT were enrolled. DaTView and DaTQUANT were used as semi-quantitative analysis tools for DAT-SPECT. RESULTS: There were significant correlations in DAT uptake between DaTView and entire regions by DaTQUANT. There was no significant difference in diagnostic accuracy between DaTView and DaTQUANT except in the posterior putamen by DaTQUANT. CONCLUSIONS: For distinguishing DLB from AD, both of DaTView and DaTQUANT software are useful. Moreover, assessing the DAT uptake in entire striatum by DaTView might be sufficient for distinguishing DLB from AD.

Correlation between clinical symptoms and striatal DAT uptake in patients with DLB.

OBJECTIVE: It is widely known that there is low striatal 123I-FP-CIT dopamine transporter-single photon emission tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). We assessed the correlation between symptom and regional low DAT uptake in the striatum. METHODS: Patients with Alzheimer's disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled. We examined the correlation between symptoms [cognitive function decline, fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD)] and regional striatal DAT uptake in the patients with DLB. RESULTS: When comparing the DLB patients with or without fluctuations, visual hallucinations, or RBD, there were no significant differences in DAT uptake in any regions of the striatum. DLB patients with parkinsonism had significantly lower DAT uptake in entire striatum, entire putamen, and anterior putamen compared to DLB patients without parkinsonism. Moreover, there was weak but significant correlation between severity of parkinsonism and DAT uptake in entire regions of the striatum in patients with DLB. There was no significant correlation between cognitive function and DAT uptake in any regions of the striatum in patients with DLB. CONCLUSIONS: In patients with DLB, only parkinsonism is associated with a reduction in striatal DAT uptake.

Oxidative stress and inflammation are associated with physical frailty in patients with Alzheimer's disease.

AIMS: Dementia is closely connected with frailty, and these two conditions are common in older adults. However, the biological mechanism that causes frailty in patients with Alzheimer's disease (AD) is not fully understood. We determined whether oxidative stress and inflammatory mechanisms could be associated with physical frailty in patients with AD. METHODS: We studied 140 elderly outpatients with mild-to-moderate AD. Frailty status was determined according to the presence of the following five measurable characteristics: weight loss, exhaustion, low physical activity, slowness and weakness. We measured oxidative stress markers, including plasma levels of diacron reactive oxygen metabolite and biological anti-oxidant potential, endogenous plasma anti-oxidants, such as albumin, bilirubin and uric acid, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epiPGF2α (8-isoprostane), and inflammatory markers, including interleukin-6 and tumor necrosis factor-α. RESULTS: Among patients, 44 (31%) were non-frail, 62 (44%) were prefrail and 34 (24%) were frail. Frail and prefrail patients were older, more likely to be women and had more comorbid medical conditions than non-frail patients. Frail or prefrail patients showed significantly higher diacron reactive oxygen metabolite and lower biological anti-oxidant potential levels, a significant decrease in bilirubin, a significant increase in urinary 8-OHdG and 8-isoprostane levels, and a significantly higher interleukin-6 level, in contrast to non-frail patients. CONCLUSIONS: Physical frailty is common in old and female AD patients with comorbid medical diseases. The present results strongly suggest that oxidative stress and inflammation are involved in the pathophysiology of frailty status in individuals with AD. Geriatr Gerontol Int 2017; 17: 913-918.

Geriatric problems correlated with cognitive decline using a screening test named "Dr. SUPERMAN" for comprehensive geriatric assessment in elderly inpatients.

AIM: We have recently developed and validated a screening test for comprehensive geriatric assessment (CGA). We investigated the prevalence of geriatric problems in elderly inpatients using CGA, and determined the relationship between geriatric problems and cognitive decline. METHODS: We enrolled consecutive elderly inpatients aged >65 years who were admitted to all of the hospital departments at Tokyo Medical University Hospital, Tokyo, Japan, between July and December 2013. We investigated the prevalence of specific geriatric problems or situations in elderly inpatients using a screening test for CGA named "Dr. SUPERMAN." We examined 3969 elderly inpatients (2211 men and 1758 women; mean age 75.5 ± 6.7 years) using CGA. Inpatients were divided into three groups by age, namely, 65-74 years, 75-84 years and ≥85 years. Inpatients were divided into the two groups of "internal medicine" and "other departments." RESULTS: Geriatric problems were more frequently found in patients who were aged ≥85 years and admitted to "internal medicine" departments. Furthermore, multiple regression analysis found cognitive decline significantly correlated with ADL decline, age, poor medication adherence, upper and lower extremity function disorder, visual/auditory disorder, and urinary disorder. In particular, cognitive decline strongly correlated with a decline in activities of daily living. CONCLUSIONS: CGA should be considered for the treatment of elderly inpatients, particularly those with cognitive decline and admitted to "internal medicine" departments. Geriatr Gerontol Int 2017; 17: 1252-1256.

Neuroimaging for diagnosing dementia with Lewy bodies: What is the best neuroimaging technique in discriminating dementia with Lewy bodies from Alzheimer's disease?

AIM: We compared the diagnostic value of four neuroimaging techniques, namely, 123 I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT), magnetic resonance imaging, perfusion SPECT and 123 I-metaiodobenzyl-guanidine myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: A total of 32 patients with probable AD and 32 patients with probable DLB were enrolled in the present study. For the comparison study, we used the specific binding ratio for DAT-SPECT, the heart-to-mediastinum ratio in the delay phase for 123 I-metaiodobenzyl-guanidine myocardial scintigraphy, z-scores in the medial occipital lobe for perfusion SPECT and z-scores of hippocampal atrophy using a voxel-based specific regional analysis system for AD for magnetic resonance imaging. RESULTS: DAT-SPECT enabled more accurate differentiation of DLB from AD than other methods. 123 I-metaiodobenzyl-guanidine myocardial scintigraphy enabled more accurate differentiation of DLB from AD than magnetic resonance imaging and perfusion SPECT. CONCLUSIONS: In agreement with the recent consensus clinical diagnostic criteria for DLB, we confirmed that the diagnostic accuracy of DAT-SPECT imaging is significantly higher than other neuroimaging techniques. Geriatr Gerontol Int 2017; 17: 819-824.

Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer's disease.

PURPOSE: (123)I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer's disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD. METHODS: Patients with AD (n = 57) and patients with DLB (n = 76) who underwent both DAT SPECT and MIBG myocardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were associated with the patterns of the abnormalities displayed on DAT SPECT and MIBG myocardial scintigraphy. RESULTS: The sensitivity and specificity of differentiating DLB from AD were 72.4 and 94.4 % by the heart to mediastinum ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding ratio on DAT SPECT, and 96.1 and 90.7 % by their combination, respectively. The combined use of DAT SPECT and MIBG myocardial scintigraphy enabled more accurate differentiation between DLB and AD compared with either DAT SPECT or MIBG myocardial scintigraphy alone. There was a significantly higher frequency of parkinsonism in the abnormal DAT SPECT group than the normal DAT SPECT group. On the other hand, there was a higher frequency of the appearance of rapid eye movement (REM) sleep behavior disorder in the abnormal MIBG uptake group than the normal MIBG uptake group. CONCLUSION: These results suggested that using a combination of these scintigraphic methods is a useful and practical approach to differentiate DLB from AD.

Comprehensive geriatric assessment in elderly patients with dementia.

AIM: We have recently developed and validated a screening test for comprehensive geriatric assessment (CGA) named "Dr. SUPERMAN". We compared the results obtained by the CGA of patients with Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies (DLB), and determined the relationship between functional deficits and clinical characteristics in each type of dementia. METHODS: We used Dr. SUPERMAN to examine patients with AD (24 men and 53 women, mean age 83.0 ± 5.1 years), VaD (10 men and 12 women, mean age 80.4 ± 5.0 years) and DLB (28 men and 20 women, mean age 81.2 ± 5.5 years). RESULTS: Patients with DLB or VaD had functional deficits more frequently than those with AD in many fields. Significant correlations between functional impairments and clinical characteristics, such as age, sex and Mini-Mental State Examination scores, in the non-AD group (including DLB and VaD) were found in more extensive fields than those in the AD group. CONCLUSIONS: Patients with dementia, particularly DLB, have several geriatric problems. Correlations between functional deficits and clinical characteristics differ between the AD group and the non-AD group. Non-AD patients of older age who are male and have advanced dementia are more likely have several functional deficits. In addition to age and severity of dementia, the type of dementia should be considered in the treatments and interventions of elderly patients with dementia.