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Background: Participant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials., Objective: To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial., Methods: In this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N., Results: Plasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p < 0.001). Age, sex, and APOE ɛ4 carrier status did not the diagnostic performance of plasma Aβ42/Aβ40 to predict amyloid PET positivity in A4 Study participants., Conclusion: Plasma Aβ42/Aβ40 may serve as a potential biomarker for predicting elevated amyloid in the brain. Utilizing blood testing over PET imaging may improve screening efficiency into clinical trials.

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial., Objective: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function., Methods: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses., Results: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75-48.2, p < 0.001)., Conclusion: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study.

Background: With increasingly aging societies, a comprehensive strategy for dementia research is important. The Organized Registration for the Assessment of dementia by the Nationwide General consortium toward Effective treatment (ORANGE) Registry is the first longitudinal multicenter prospective trial-ready cohort in Japan., Objective: To establish a large cohort for use in clinical trials and research in Japan., Methods: This registry, based on communities, hospitals, and nursing homes, covers three dementia stages (preclinical, mild cognitive impairment [MCI], and advanced dementia), and includes more than 30 hospitals. We analyzed enrollment and 1-year follow-up data for disease progression., Results: There were 1450 registered patients (649 men, 801 women; mean age, 77.92±6.70 years; mean Mini-Mental State Examination [MMSE] score, 25.19±2.76). The conversion rates from MCI to dementia and MCI to normal were 14.3% and 1.1%, respectively. High Clinical Dementia Rating score (odds ratio [OR] = 11.085, 95% confidence interval [CI]:1.619-75.913, p = 0.014), low MMSE score (OR = 0.835, 95% CI: 0.761-0.917, p < 0.001), high Geriatric Depression Scale score (OR = 1.093, 95% CI: 1.005-1.189, p = 0.038), and low body mass index (OR = 0.895, 95% CI: 0.829-0.967, p = 0.005) at enrollment were significant factors for conversion., Conclusion: The ORANGE MCI Registry is an established registry that facilitates creation of trial-ready cohorts to accelerate promotion of clinical trials with low reversion rates as it originates from a hospital. One-year follow-up analysis suggested assessing various factors for conversion risk. Further analyses will be possible in future with registry expansion. We will continue to refine this registry, including how it can be used more efficiently.

Importance: Blood-based tests for brain amyloid-β (Aβ) pathology are needed for widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening and monitoring of treatment responses in clinical trials., Objective: To compare the performance of plasma Aβ42/40 measured using 8 different Aβ assays when detecting abnormal brain Aβ status in patients with early AD., Design, Setting, and Participants: This study included 182 cognitively unimpaired participants and 104 patients with mild cognitive impairment from the BioFINDER cohort who were enrolled at 3 different hospitals in Sweden and underwent Aβ positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) and plasma collection from 2010 to 2014. Plasma Aβ42/40 was measured using an immunoprecipitation-coupled mass spectrometry developed at Washington University (IP-MS-WashU), antibody-free liquid chromatography MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma Aβ42/40 was also measured using an IP-MS-based method from Shimadzu in 200 participants (IP-MS-Shim) and an IP-MS-based method from the University of Gothenburg (IP-MS-UGOT) and another immunoassay from Quanterix (IA-Quan) among 227 participants. For validation, 122 participants (51 cognitively normal, 51 with mild cognitive impairment, and 20 with AD dementia) were included from the Alzheimer Disease Neuroimaging Initiative who underwent Aβ-PET and plasma Aβ assessments using IP-MS-WashU, IP-MS-Shim, IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays., Main Outcomes and Measures: Discriminative accuracy of plasma Aβ42/40 quantified using 8 different assays for abnormal CSF Aβ42/40 and Aβ-PET status., Results: A total of 408 participants were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF Aβ42/40 in the whole cohort, plasma IP-MS-WashU Aβ42/40 showed significantly higher accuracy (area under the receiver operating characteristic curve [AUC], 0.86; 95% CI, 0.81-0.90) than LC-MS-Arc Aβ42/40, IA-Elc Aβ42/40, IA-EI Aβ42/40, and IA-N4PE Aβ42/40 (AUC range, 0.69-0.78; P < .05). Plasma IP-MS-WashU Aβ42/40 performed significantly better than IP-MS-UGOT Aβ42/40 and IA-Quan Aβ42/40 (AUC, 0.84 vs 0.68 and 0.64, respectively; P < .001), while there was no difference in the AUCs between IP-MS-WashU Aβ42/40 and IP-MS-Shim Aβ42/40 (0.87 vs 0.83; P = .16) in the 2 subcohorts where these biomarkers were available. The results were similar when using Aβ-PET as outcome. Plasma IPMS-WashU Aβ42/40 and IPMS-Shim Aβ42/40 showed highest coefficients for correlations with CSF Aβ42/40 (r range, 0.56-0.65). The BioFINDER results were replicated in the Alzheimer Disease Neuroimaging Initiative cohort (mean [SD] age, 72.4 [5.4] years; 43.4% women), where the IP-MS-WashU assay performed significantly better than the IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays but not the IP-MS-Shim assay., Conclusions and Relevance: The results from 2 independent cohorts indicate that certain MS-based methods performed better than most of the immunoassays for plasma Aβ42/40 when detecting brain Aβ pathology.

Background: There is a dearth of longitudinal data on body composition, function, and physical performance in persons with Alzheimer's disease (AD)., Objectives: The aim was to describe the trajectories of function, body composition, and physical performance in older adults with AD., Methods: In this retrospective cohort study, data were collected from older adults (n=1402) diagnosed with AD (mean age: 78.1 y old, women: 69.3%). Cognitive function was assessed using the mini-mental state examination. Proxy-reported instrumental and basic activities of daily living were assessed using the Lawton and Barthel indexes. Body composition was assessed using bioelectrical impedance analysis. Physical performance was assessed using the timed up and go test and grip strength., Results: Median (interquartile range) of follow-up time was 2.2 (1.2 to 3.6) years. Participants' mini-mental state examination score, Barthel index, and Lawton index declined over time. Skeletal muscle mass index and physical performance (timed up and go test and grip strength) decreased, while fat mass index increased with time. No significant changes or slight decline in weight and body mass index was observed., Conclusions: Muscle mass and physical performance are likely to decline in older adults with AD. Clinicians should assess muscle mass and physical performance trajectories regularly in these patients and intervene appropriately., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

We examined the nutritional status and its association with behavioral psychiatric symptoms of dementia (BPSD) among 741 memory clinic patients (normal cognition (NC), 152; mild cognitive impairment (MCI), 271; early-stage Alzheimer disease (AD), 318). Nutritional status and BPSD were assessed using the Mini Nutritional Assessment Short-Form (MNA-SF) and the Dementia Behavior Disturbance Scale (DBD), respectively. Compared to subjects with NC, more subjects with MCI and early-stage AD were at risk of malnutrition (MNA-SF, 8-11: NC, 34.2%; MCI, 47.5%; early-stage AD, 53.8%) and were malnourished (MNA-SF, 0-7: NC, 4.6%; MCI, 5.9%; early-stage AD, 8.2%). Among patients with MCI or early-stage AD, those at risk of/with malnutrition showed higher DBD scores than those well-nourished (12.7 ± 9.0 vs. 9.5 ± 7.3; p < 0.001). Moreover, analysis of covariance adjusting for confounders showed that nutritional status was significantly associated with specific BPSD, including "verbal aggressiveness/emotional disinhibition" (F = 5.87, p = 0.016) and "apathy/memory impairment" (F = 15.38, p < 0.001), which were revealed by factor analysis of DBD. Our results suggest that malnutrition is common among older adults with mild cognitive decline, and possibility that nutritional problems are associated with individual BPSD.

Objective: The aim of this study was to clarify the association of physical frailty with behavioral and psychological symptoms of dementia (BPSD) and caregiver burden in patients with Alzheimer's disease (AD)., Methods: The subjects were 1,193 AD patients who presented to the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan during the period from October 2010 to February 2015 (mean ± SD age = 78.8 ± 6.3 years; female, 68.6%). AD was diagnosed based on the criteria of the National Institute on Aging and Alzheimer's Association workgroups. The Frailty Index (FI) was calculated as the ratio of actual to 38 potential deficits. BPSD and caregiver burden were assessed by using the Dementia Behavior Disturbance Scale (DBD) and the Japanese version of Zarit Burden Interview (J-ZBI). Multiple linear regression analyses and structural equation modeling (SEM) were performed to examine the relationship between the FI, DBD, and J-ZBI., Results: The subjects' mean FI score was 0.16 ± 0.10, with 663 (55.6%) and 198 (16.6%) subjects shown to be pre-frail (0.08 ≤ FI < 0.25) and frail (FI ≥ 0.25), respectively. Multiple linear regression analyses and SEM showed that the FI was independently associated with both DBD (β = 0.30, P < .001) and J-ZBI (β = 0.13, P < .001). Moreover, when the FI was considered as a categorical variable, even pre-frailty was associated with increased DBD score (β = 0.16, P < .001) and J-ZBI score (β = 0.09, P = .003)., Conclusions: The presence of not only physical frailty but also pre-frailty, as determined by the FI, could increase BPSD and caregiver burden in patients with AD., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objectives: We investigated the differences in the physical function test results across stages from normal cognition (NC) to moderate Alzheimer disease (AD) and how risk factors of physical function decline are correlated with the physical function test results., Design: A cross-sectional study of outpatients at the Memory Disorder Outpatient Center of Japan's National Center of Geriatrics and Gerontology., Participants: We enrolled 882 individuals aged ≥65 diagnosed with NC (n = 210), amnestic mild cognitive impairment (aMCI; n = 273), mild AD (n = 181) or moderate AD (n = 197)., Measurements: We measured the participants' results for functional reach (FR), the one-leg standing (OLS) test, the Timed Up and Go (TUG) test, tandem gait (TG), and grip strength (GS). A one-way analysis of covariance (ANCOVA) was used to identify significant differences among the groups' results on the physical function tests, controlling for age, sex, educational year, Mini-Nutritional Assessment, senior activity and exercise frequency, low-density lipoprotein, body mass index, free-fat mass index, and assistance for the TUG test. Multiple regression analysis was also used to investigate the correlation between these covariates and physical function tests results., Results: The ANCOVA showed that FR, OLS, and TG were significantly worse among the individuals with aMCI, mild AD, or moderate AD compared with NC. However, TUG was significantly worse only in the moderate AD group compared with the NC, aMCI, and mild AD group. Multiple regression analysis showed that aging was correlated with poorer scores on all physical function tests, women had poorer scores on FR and GS than men, and low frequency of senior activity was significantly correlated with poorer scores on FR, OLS, and TG., Conclusion: Postural impairment and instability on TG was seen in earlier AD stages compared with instability on TUG. As were the covariates of age and sex, senior activity frequency was significantly related to 2 or more physical function tests., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Instrumental activities of daily living (IADL) start to decline during the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). Cognitive and physical decline are involved in the loss of functional independence. However, little is known about AD-related neural change that leads to IADL impairment. The purpose of this study was to clarify the effects of regional white matter hyperintensity (WMH) on IADL impairment in persons with AD and aMCI., Methods: The participants were 347 female subjects aged 65-85 years diagnosed with AD (n = 227), aMCI (n = 44) or normal cognition (n = 76). IADL was assessed by the Lawton Index. Cognition, mood and mobility function were evaluated by comprehensive geriatric assessment batteries. WMH and brain atrophy were analyzed with brain magnetic resonance imaging, using an automatic segmentation program. Regional WMH was measured in the frontal, temporal, occipital and parietal lobes., Results: Ability to carry out IADL of shopping, food preparation, mode of transportation, responsibility for own medication, and ability to handle finances was obviously impaired in the early stage of AD. Frontal WMH was specifically associated with disability to do shopping and food preparation even after adjusting for several confounders including brain atrophy., Conclusions: IADL subcategories were differentially impaired along with cognitive status in persons with AD and aMCI. Frontal WMH was an important predictor of impaired ability to do shopping and food preparation. A preventive strategy for WMH might lead to suppression of IADL disability and slow the progression of AD.

Background: Urinary incontinence (UI) is frequently observed in patients with Alzheimer's disease (AD). Although previous works highlight the association between frontal lobe-related function and UI, causal relationship is unclear., Objects: To clarify the longitudinal association between frontal lobe function and the incidence of UI at 1 year in patients with AD., Methods: The subjects were 215 continent AD patients who attended the Memory Clinic of the National Center for Geriatrics and Gerontology of Japan during the period from March 2011 to December 2014. The absence or presence of UI was operationally assigned by the dementia behavior disturbance scale subscale, which was completed by the patients' caregivers. Frontal lobe function was assessed using the Frontal Assessment Battery (FAB). Other confounding factors including demographic data, cognitive status, vitality, mood, physical performance, and use of medication (cholinesterase inhibitors, calcium channel blockers [CCBs], diuretics, alpha blockers and anticholinergic drugs) were assessed., Results: During 1-year follow up (mean: 377.4±83.7 days), the incidence of UI was 12.1% (n = 26). Patients with UI had significantly lower FAB performance at baseline (no UI versus UI = 9.3±2.8 versus 7.8±2.7). In multivariate analysis, stepwise logistic regression analysis demonstrated that FAB (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.66-0.94) and the use of CCB (OR = 2.72, 95% CI = 1.09-6.77) were significantly associated with UI at 1 year., Conclusion: The results of study indicate that frontal lobe dysfunction is predictor for UI in patients with AD.

Aim: Lower urinary tract symptoms often limit activities of daily life and impair quality of life in the elderly. The purpose of the present study was to determine whether regional white matter hyperintensity (WMH) can predict lower urinary tract symptoms in elderly with amnestic mild cognitive impairment or Alzheimer's disease., Methods: The participants were 461 patients aged 65-85 years diagnosed with amnestic mild cognitive impairment or Alzheimer's disease. Patients and their caregivers were asked about symptoms of lower urinary tract symptoms (urinary difficulty, frequency and incontinence). Cognition, behavior and psychological symptoms of dementia and medication were evaluated. WMH and brain atrophy were analyzed using an automatic segmentation program. Regional WMH was evaluated in the frontal, parietal, temporal and occipital lobes., Results: Patients with urinary incontinence showed significantly greater volume of WMH. WMH increased with age, especially in the frontal lobe. WMH in the frontal lobe was closely associated with urinary incontinence after adjustment for brain atrophy and classical confounding factors., Conclusions: Frontal WMH was a predictive factor for urinary incontinence in older adults with amnestic mild cognitive impairment or Alzheimer's disease. Urinary incontinence in demented older adults is not an incidental event, and careful insight into regional WMH on brain magnetic resonance imaging might greatly help in diagnosing individuals with a higher risk of urinary incontinence., (© 2015 Japan Geriatrics Society.)

Background: To date, very little is known about the nature of sarcopenia in subjects with cognitive impairment. The aims of this study were firstly to clarify the prevalence of sarcopenia at various stages of cognitive impairment, and secondly to examine factors related to sarcopenia in men and women with cognitive impairment., Method: The subjects were 418 outpatients (normal cognition; NC: 35, amnestic mild cognitive impairment; aMCI: 40, Alzheimer disease; AD: 343) who attended the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan during the period from October 2010 to July 2014. Cognitive status, vitality, depressive mood, body mass index, hand grip strength, timed up and go test, skeletal muscle mass and serum levels of 25-hydroxyvitamin D, albumin and creatinine were assessed. Sarcopenia was defined as the presence of both poor muscle function (low physical performance or low muscle strength) and low muscle mass. We performed the univariate and multivariate logistic regression analyses to explore factors associated with sarcopenia., Results: The overall prevalence of sarcopenia was 21.1% (NC = 8.6%, aMCI = 12.5%, AD = 23.3%). In both sexes, factors associated with sarcopenia were age (P < .01), body mass index (P < .001) and vitality (P < .05). In women, serum level of 25-hydroxyvitamin D was associated with sarcopenia (P < .05)., Conclusion: Low vitality could be a dementia-specific risk factor for sarcopenia. Prevention of sarcopenia in patients with cognitive impairment should be approached from physical and psychologic points of view.

Background: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease., Methods: We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative., Results: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups., Conclusion: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.

Aim: The clinical management of diabetic elderly patients with Alzheimer's disease (AD) is hindered by several difficulties. The present study aimed to clarify the clinical characteristics and pathophysiological properties of AD in diabetic older adults., Methods: A total of 91 patients with type 2 diabetes mellitus and 161 non-diabetic individuals who were diagnosed with AD were recruited. Diabetic patients were classified into two groups with glycated hemoglobin (HbA1c) < 7.0% or ≥ 7.0%. The demographics, cognition, daily-life function, metabolic changes, treatment, and behavioral and psychological symptoms of dementia (BPSD), as well as brain pathophysiology, were compared among the three groups., Results: Patients with higher HbA1c had increased diabetic vascular complications and impaired activities of daily living with decreased levels of serum high-molecular-weight adiponectin and 25-hydroxyvitamin D. Although cognitive status was similar among the three groups, BPSD, including apathy, overeating and excessive daytime sleeping appeared to be increased in the patients with HbA1c ≥ 7.0%. The frequency of apolipoprotein E4 carriers and of posterior cerebral hypoperfusion (AD-pattern) on single-photon emission computed tomography in poorly controlled diabetic subjects was similar to that in non-diabetic AD patients, whereas diabetic patients with HbA1c <7.0% included fewer apolipoprotein E4 carriers and fewer patients with an AD pattern on single-photon emission computed tomography., Conclusion: Subtypes of older diabetic patients with AD were identified based on clinical features and brain pathophysiology. Physical and psychological complications of dementia are prevalent in patients with higher HbA1c. It seems likely that difficulties in the management of diabetes with AD are due not only to non-adherence to diabetes treatment, but also several symptoms and pathophysiological characteristics of dementia., (© 2014 Japan Geriatrics Society.)

Aim: To investigate factors associated with caregiver burden (CB) in persons caring for older adults with various cognitive stages of Alzheimer's disease (AD)., Methods: Participants were 1127 outpatients and their caregivers. Participants comprised 120 older adults with normal cognition (NC), 126 with amnestic mild cognitive impairment (aMCI) and 881 with AD. AD patients were subclassified into four groups by Mini-Mental State Examination (MMSE) score: AD29-24 (n = 117), AD23-18 (n = 423), AD17-12 (n = 254) and AD11-0 (n = 87). Participants and their caregivers underwent comprehensive geriatric assessment batteries including Zarit Burden Interview (ZBI) Barthel Index, Lawton Index, Dementia Behavior Disturbance Scale (DBD) to evaluate CB, Instrumental and Basic Activity of Daily Living (IADL/BADL), and Behavioral and Psychological Symptoms of Dementia (BPSD). The comorbidity of geriatric syndrome and the living situation of the patient/caregiver were also assessed., Results: ZBI score was higher in patients with lower MMSE score. Multivariate regression analysis identified that DBD was consistently associated with CB in all patients; symptoms related to memory deficit were related to CB in aMCI; differential IADL, such as inability to use a telephone, use transportation, manage finances, shop, cook and take responsibility for own medication, were related to CB in AD29-24, AD23-18 and AD17-12, and geriatric syndrome including falls and motor disturbance, sleep problems, urinary incontinence, and fatigue was related to CB in AD23-18 and AD17-12., Conclusions: Multiple factors including BPSD, impaired life function and geriatric syndrome were cognitive stage-dependently associated with CB. Preventive treatment of BPSD and comorbidity, and effective assistance for IADL deficits could contribute to alleviation of CB., (© 2014 Japan Geriatrics Society.)

Objectives: Preventive strategy for falls in demented elderly is a clinical challenge. From early-stage of Alzheimer's disease (AD), patients show impaired balance and gait. The purpose of this study is to determine whether regional white matter lesions (WMLs) can predict balance/gait disturbance and falls in elderly with amnestic mild cognitive impairment (aMCI) or AD., Design: Cross-sectional., Settings: Hospital out-patient clinic., Participants: One hundred sixty-three patients diagnosed with aMCI or AD were classified into groups having experienced falls (n = 63) or not (n = 100) in the previous year., Measurements: Cognition, depression, behavior and psychological symptoms of dementia, medication, and balance/gait function were evaluated. Regional WMLs were visually analyzed as periventricular hyperintensity in frontal caps, bands, and occipital caps, and as deep white matter hyperintensity in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalamus, and brain stem. Brain atrophy was linearly measured., Results: The fallers had a greater volume of WMLs and their posture/gait performance tended to be worse than nonfallers. Several WMLs in particular brain regions were closely associated with balance and gait impairment. Besides polypharmacy, periventricular hyperintensity in frontal caps and occipital WMLs were strong predictors for falls, even after potential risk factors for falls were considered., Conclusions: Regional white matter burden, independent of cognitive decline, correlates with balance/gait disturbance and predicts falls in elderly with aMCI and AD. Careful insight into regional WMLs on brain magnetic resonance may greatly help to diagnose demented elderly with a higher risk of falls., (Copyright © 2014 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is the most common and devastating dementia. Simple and practical biomarkers for AD are urgently required for accurate diagnosis and to facilitate the development of disease-modifying interventions. The subjects for the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB-positive (PiB+) individuals, including cognitively healthy controls (HC), and mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB-) HC participated. Employing our novel highly sensitive immunoprecipitation-mass spectrometry, we measured plasma amyloid β-proteins (Aβs; Aβ1-40 and Aβ1-42) and Aβ-approximate peptides (AβAPs), which were cleaved from amyloid precursor protein (APP). Among the AβAPs, APP669-711 appeared to be a good reference for deciphering pathological change of Aβ1-42. We evaluated the performance of the ratio of APP669-711 to Aβ1-42 (APP669-711/Aβ1-42) as a biomarker. APP669-711/Aβ1-42 significantly increased in the PiB+ groups. The sensitivity and specificity to discriminate PiB+ individuals from PiB- individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely surrogates cerebral amyloid deposition.

Objective: The aim of this study was to identify a useful neuropsychological instrument for making a differential clinical diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB)., Methods: We examined 402 AD and 38 DLB patients with neuropsychological tests that covered general cognition, frontal lobe cognitive function, non-verbal abstract reasoning, working memory and attention, and verbal memory. Discriminant analysis using a stepwise method was performed to identify the measures best able to discriminate between AD and DLB., Results: The AD patients performed significantly worse than the DLB patients on orientation to time, delayed recall subtests on the Mini-Mental State Examination, and logical memory subtests 1 and 2 of the Revised Wechsler Memory Scale. The DLB patients performed significantly worse than the AD patients on the attention, repetition, and pentagon copying subtests of the Mini-Mental State Examination, the constructional praxis subtests of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, the Frontal Assessment Battery total score, Raven's Coloured Progressive Matrices (RCPM) sets A, AB, and B, and backward digit span. Discriminant analyses between AD and DLB established the key variables as Logical Memory 1, Logical Memory 2, backward digit span, RCPM, and delayed recall on the Mini-Mental State Examination. We inferred the AD-DLB discriminant index from the following discriminant analyses: AD-DLB discriminant index = (Backward digit span score + RCPM set B score) - (Logical Memory 1 score + Logical Memory 2 score), which offered a highly favourable value for diagnostic utility., Conclusions: The AD-DLB discriminant index, consisting of backward digit span, RCPM set B, and logical memory 1 and 2, is useful to differentiate between AD and DLB., (© 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.)

Aim: The oral management of dementia patients is critical to prevent aspiration pneumonia and maintain patients' quality of life. However, the oral health status of these patients has not been adequately elucidated thus far, and it is not well understood how oral care is managed for mild dementia patients. To provide effective oral management for mild dementia patients, we investigated their oral health status and how their oral care was managed., Methods: We enrolled 10 outpatients aged 66 to 85 years old who regularly visited our neurology clinic. All of the patients had mild dementia. We conducted 2 questionnaire studies regarding oral hygiene and dentures and performed an oral examination to evaluate the changes in oral hygiene status over time. The questionnaire was designed to explore the understanding of oral hygiene methods. Oral care instructions were given to the patients and their caregivers. Three surveys of 2 questionnaires each were performed. The survey was conducted at the initial visit, and 3 months and 6 months later., Results: Although oral care instructions were given to the patients and their caregivers, neither their plaque index nor gingival index showed major improvement over time. Based on the results of these questionnaires, patient awareness of oral hygiene did not change over time., Conclusion: It is difficult for patients with mild dementia to perform oral care by themselves. It is important to make oral hygiene habits second nature in middle-aged patients, to introduce oral management to be performed by the caregivers and to promote early dental intervention to improve and maintain oral hygiene status in mild dementia patients.

Aim: The clinical guidelines for idiopathic normal pressure hydrocephalus (iNPH) in Japan recommend cerebrospinal fluid (CSF) drainage. The positive response rate of the diagnostic CSF drainage is not very high because brain MRI findings of Alzheimer disease (AD) are similar to those of iNPH. Therefore, we sought to determine simple, quantitative indexes of head MRI to differentiate iNPH from AD and to predict positive response of the CSF drainage in possible iNPH., Methods: Eighteen patients with the clinical criteria of possible iNPH who had undergone diagnostic CSF drainage were evaluated. Nineteen patients with the clinical criteria of probable AD were used as controls. VSRAD, Evans index, and previously reported indicators were measured on brain MRI in all patients. These parameters were compared between AD and iNPH, and between iNPH responders and non-responders., Results: VSRAD, Evans index, bifrontal index, width and height of the temporal horn, and the maximum height of the Sylvian fissure were higher in iNPH than AD. The cutoff value of the bifrontal index, width and height of the temporal horn, and maximum height of the Sylvian fissure were 0.31, 6.0 mm, 3.13 mm, and 7.6 mm, respectively. The minimum thickness of the medial temporal lobe was higher in the CSF drainage responders than the non-responders. The cutoff value of the minimum thickness of the medial temporal lobe was 11.0 mm., Conclusions: Our results suggest that simple image indexes of brain MRI could distinguish iNPH from AD and predict positive response to CSF drainage in iNPH.

Aim: To clarify the area in the brain related to responsible for vitality and volition., Methods: We studied 123 outpatients (39 men, 84 women, 77.7+/-6.7 years old) who visited the Center for comprehensive care on memory disorders in Kyorin University Hospital. No patients were prescribed with anti-depressants, anti-anxiety agents, psychomimetics, acetylcholinesterase inhibitors, Chinese herbal medicines or cerebrovascular circulation modifying drugs. Patients with frontotemporal dementia or depression were excluded. ADL-related vitality and volition was measured by a vitality index. Cerebral brain blood flow was measured by single photon emission computed tomography (99mTc-ECD SPECT). Relative blood flow changes were calculated by Statistical Parametric Mapping (SPM). Absolute blood flow changes were calculated by a three-dimensional stereotaxic ROI template on anatomically standardised 99mTc-ECD SPECT (3D SRT). Statistically significant correlations between semi-quantitatively measured scores of vitality index and blood flow changes in SPM and 3D-SRT were tested and displayed on a brain map., Results: Analysis of relative and absolute blood flow showed that the common responsible area in the brain related to vitality was the frontal lobe, fronto-cingulate gyrus, temporal lobe, basal ganglia (caudate nucleus) and thalamus. Blood flow changes in the orbital gyrus were strongly correlated with vitality index specially in the frontal lobe., Conclusion: ADL-related vitality is affected mainly by the blood flow in the frontal-subcortical circuit. However, deep white matter was also important to determine vitality and volition.

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are exhibited in most patients with Alzheimer disease (AD). Although white matter hyperintensity (WMH) is often observed with AD, the precise role of WMH in BPSD remains unclear. The current study aimed to identify the impact of regional WMH on specific features of BPSD in persons with mild to moderate AD and amnestic mild cognitive impairment (aMCI). Methods: A sample of 256 female outpatients with AD (n = 217) and aMCI (n = 39) were recruited. We assessed BPSD using the Dementia Behavior Disturbance Scale. WMH and brain atrophy were evaluated using an automatic segmentation program. Regional WMH was evaluated as periventricular hyperintensity (PVH) and deep WMH in frontal, temporal, occipital, and parietal lobes. Results: Whole-brain WMH was associated with verbal aggressiveness. In multivariate analysis, PVH in the frontal lobe was independently associated with verbal aggressiveness after adjustment for brain atrophy and clinical confounders. Conclusion: The current results indicated that PVH in the frontal lobe was independently associated with verbal aggressiveness. [ABSTRACT FROM AUTHOR]