ABSTRACT
AIM: Yokukansan (YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia (BPSD). The present study is the first double-blind, randomized, placebo-controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer's disease (AD). METHODS: A total of 22 sites consisting of clinics, hospitals and nursing homes participated. A total of 145 patients with AD were randomized. Active YKS (7.5 g/day) and placebo were supplied to 75 and 70 participants, respectively. The primary outcome measure was the 4-week change in total score of the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q), an instrument that evaluates BPSD. Secondary outcome measures included 12-week changes in NPI-Q scores, changes in NPI-Q subcategory scores and total scores of the Mini-Mental-State Examination. RESULTS: Four-week changes in NPI-Q total scores did not differ significantly between the treatment and placebo groups. There were also no significant differences between groups in 12-week changes in total NPI-Q scores, NPI-Q subcategory scores or total Mini-Mental-State Examination scores. However, a subgroup with fewer than 20 points on the Mini-Mental-State Examination at baseline showed a greater decrease in "agitation/aggression" score in the YKS group than in the placebo group (P = 0.007). No serious adverse effects were observed during the study. CONCLUSIONS: Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.
Subject(s)
Alzheimer Disease/psychology , Behavioral Symptoms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Mental Disorders/drug therapy , Phytotherapy , Aged , Aged, 80 and over , Behavioral Symptoms/etiology , Double-Blind Method , Female , Humans , Male , Mental Disorders/etiology , Neuropsychological TestsABSTRACT
Adiponectin (APN) is protective in animal models of neurodegenerative diseases, but the role of APN in human brain has not been established. Using an enzyme-linked immunosorbent assay, we found that APN was significantly decreased in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), compared to those in patients with mild cognitive impairment (MCI) and in normal controls (NC), despite elevation of APN in serum of patients with MCI and AD compared to that in NC. The discrepancy of CSF APN from serum APN in AD may suggest some critical actions of APN in the pathogenesis of AD. Indeed, it was histologically observed that APN was co-localized with tau in neurofibrillary tangles and immunoblot analysis showed that the functional trimers of APN were significantly decreased in AD compared to those in NC. Collectively, a loss of function of APN may be involved in the pathogenesis of AD.
Subject(s)
Adiponectin/cerebrospinal fluid , Alzheimer Disease/etiology , Adiponectin/analysis , Adiponectin/blood , Adiponectin/deficiency , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/pathology , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brain/pathology , Brain Chemistry , Case-Control Studies , Cognitive Dysfunction/blood , Cognitive Dysfunction/cerebrospinal fluid , Enzyme-Linked Immunosorbent Assay , Female , Humans , MaleSubject(s)
Cognitive Dysfunction/epidemiology , Disasters , Earthquakes , Housing , Aged , Aged, 80 and over , Dementia/prevention & control , Female , Geriatric Assessment , Humans , Japan/epidemiology , Male , Transients and MigrantsABSTRACT
AIM: Although diabetes mellitus (DM) is considered to be one of the most consistent risks for developing dementia, it is not known if the pathology in dementia patients with DM is similar to or distinct from typical pathological features of Alzheimer's disease (AD). To discover the mechanism of developing dementia in AD patients with DM in a living state, we studied the distribution of amyloid ß (Αß) protein of diabetic AD patients. METHODS: To evaluate the accumulation of Aß, we examined 14 normal controls, four diabetic patients with AD and 11 non-diabetic patients with AD by positron emission tomography (PET) using BF-227, a currently developed Aß tracer. RESULTS: The analysis of PET images among the three groups showed an abundant aggregated Aß accumulation in the cerebral cortex of both AD patients with and without DM. The extent and distributions of BF-227 accumulation in diabetic AD patients were not significantly different from these of non-diabetic AD patients. CONCLUSION: These results suggest that the degree and extent of Aß deposition is not significantly different between AD with DM and AD alone.
Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Diabetes Complications/diagnostic imaging , Diabetes Complications/metabolism , Positron-Emission Tomography , Aged , Benzoxazoles , Brain/diagnostic imaging , Brain/metabolism , Case-Control Studies , Female , Humans , Male , Middle Aged , ThiazolesSubject(s)
Alzheimer Disease/complications , Cholinesterase Inhibitors/administration & dosage , Deglutition Disorders/drug therapy , Deglutition Disorders/etiology , Phenylcarbamates/administration & dosage , Aged, 80 and over , Female , Humans , Rivastigmine , Severity of Illness Index , Transdermal PatchSubject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cognition/drug effects , Dementia/prevention & control , Hypertension/drug therapy , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Blood-Brain Barrier/physiology , Dementia/epidemiology , Dementia/etiology , Female , Humans , Hypertension/complications , Hypertension/metabolism , Incidence , Male , Risk FactorsSubject(s)
Aged/psychology , Caregivers/psychology , Homicide , Aged, 80 and over , Female , Humans , Independent Living , Japan , MaleABSTRACT
BACKGROUND: The down-regulation of the cough reflex in patients with aspiration pneumonia can involve both cortical facilitatory pathways for cough and medullary reflex pathways. In order to study the possible involvement of the supramedullary system in the down-regulation of cough reflex, we evaluated the urge-to-cough in patients with aspiration pneumonia. METHODS: Cough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least a history of aspiration pneumonia and age-matched healthy elderly people. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough scores at the concentration of C2 and C5, and at the concentration of two times dilution of C2 (C2/2) and C5 (C5/2) were estimated for each subject. RESULTS: Both C2 and C5 in the control subjects were significantly greater than those for patients with aspiration pneumonia. There were no significant differences in the urge-to-cough at C2 and C5 between control subjects and patients with aspiration pneumonia. However, the urge-to-cough scores at both C2/2 and C5/2 in patients with aspiration pneumonia were significantly lower than those in control subjects. The number of coughs at C5/2 was significantly greater in the control subjects than those in the patients with aspiration pneumonia whereas the number of coughs at C2/2 did not show a significant difference between the control subjects and the patients with aspiration pneumonia. CONCLUSION: The study suggests the involvement of supramedullary dysfunction in the etiology of aspiration pneumonia in the elderly. Therefore, restoration of the cough motivation system could be a new strategy to prevent aspiration pneumonia in the elderly.
