-
1.
Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.
Kudoh, C, Arita, R, Honda, M, Kishi, T, Komatsu, Y, Asou, H, Mimura, M
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society. 2016;(2):85-92
Abstract
BACKGROUND Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.
-
2.
Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer's disease patients and control subjects.
Varrone, A, Oikonen, V, Forsberg, A, Joutsa, J, Takano, A, Solin, O, Haaparanta-Solin, M, Nag, S, Nakao, R, Al-Tawil, N, et al
European journal of nuclear medicine and molecular imaging. 2015;(3):438-46
Abstract
PURPOSE Imaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer's disease (AD). [(18)F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [(18)F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [(18)F]FEMPA binding in AD patients than in controls could be detected in vivo. METHODS Ten AD patients (five men, five women; age 66.9 ± 7.3 years; MMSE score 25.5 ± 2.5) and seven controls (three men, four women; age 63.7 ± 7.2 years, MMSE score 29.3 ± 1.0) were studied using [(18)F]FEMPA at Turku (13 subjects) and at Karolinska Institutet (4 subjects). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [(3)H]PK11195 in seven controls and eight AD patients. Cortical and subcortical regions of interest were examined. Quantification was performed using a two-tissue compartment model (2TCM) and Logan graphical analysis (GA). The outcome measure was the total distribution volume (V T). Repeated measures analysis of variance was used to assess the effect of group and TSPO binding status on V T. RESULTS Five AD patients and four controls were high-affinity binders (HABs). Three AD patients and three controls were mixed-affinity binders. V T estimated with Logan GA was significantly correlated with V T estimated with the 2TCM in both controls (r = 0.97) and AD patients (r = 0.98) and was selected for the final analysis. Significantly higher V T was found in the medial temporal cortex in AD patients than in controls (p = 0.044) if the TSPO binding status was entered as a covariate. If only HABs were included, significantly higher V T was found in the medial and lateral temporal cortex, posterior cingulate, caudate, putamen, thalamus and cerebellum in AD patients than in controls (p < 0.05). CONCLUSION [(18)F]FEMPA seems to be a suitable radioligand for detecting increased TSPO binding in AD patients if their binding status is taken into account.
-
3.
The influence of nutritional supplement drinks on providing adequate calorie and protein intake in older adults with dementia.
Allen, V, Methven, L, Gosney, M
The journal of nutrition, health & aging. 2013;(9):752-5
-
-
Free full text
-
Abstract
OBJECTIVES Investigate the impact of the provision of ONS on protein and energy intake from food and ability to meet protein and calorie requirements in people with dementia. DESIGN After consent by proxy was obtained, participants took part in a cross over study comparing oral intake on an intervention day to an adjacent control day. SETTING The study occurred in Nursing homes and hospitalised settings. PARTICIPANTS Older adults with dementia over the age of 65 were recruited. 26 participants (aged 83.9+/-8.4years, MMSE 13.08+/-8.13) took part. Intervention (if any): On the intervention day nutritional supplement drinks were provided three times. Each drink provided 283.3+/-41.8 Kcal of energy and 13.8+/-4.7g of protein. Supplements were removed approximately 1 hour before meals were served and weighed waste (g) was obtained. MEASUREMENTS Intake of food consumed was determined on intervention and control days using the quartile method (none, quarter, half, three quarters, all) for each meal component. RESULTS More people achieved their energy and protein requirements with the supplement drink intervention with no sufficient impact on habitual food consumption. CONCLUSION Findings from these 26 participants with dementia indicate that supplement drinks may be beneficial in reducing the prevalence of malnutrition within the group as more people meet their nutritional requirements. As the provision of supplement drinks is also demonstrated to have an additive effect to consumption of habitual foods these can be used alongside other measures to also improve oral intake.
-
4.
The effect of HMG-CoA reductase inhibitors on cognition in patients with Alzheimer's dementia: a prospective withdrawal and rechallenge pilot study.
Padala, KP, Padala, PR, McNeilly, DP, Geske, JA, Sullivan, DH, Potter, JF
The American journal of geriatric pharmacotherapy. 2012;(5):296-302
Abstract
BACKGROUND Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. OBJECTIVE The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline. METHODS A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. RESULTS At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. CONCLUSIONS This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.
-
5.
[Effect of compound Polygonum multiflorum extract on Alzheimer's disease].
Chen, L, Huang, J, Xue, L
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2010;(6):612-5
Abstract
OBJECTIVE To observe the clinical effect of compound Polygonum multiflorum extract on Alzheimer's disease (AD). METHODS We collected 209 AD patients, among whom 120 were treated with compound Polygonum multiflorum extract as a treatment group, 60 were treated with Polygonum multiflorum extract as a Chinese herb control group, and 29 were treated with Naofukang as a western medicine control group. The scores for the Mini-Mental State Examination (MMSE), Ability of Daily Living Scale (ADL) and the therapeutic effect were assessed and compared before and after the 12 week treatment. RESULTS After the treatment the scores for MMSE and ADL were improved in all groups. The scores of MMSE and ADL in the compound Polygonum multiflorum extract treatment group were significantly improved compared with the Chinese herb control group and the western medicine control group (P < 0.01). The total effective rate of 93.33% in the compound Polygonum multiflorum extract treatment group was better than 73.33% in the Chinese herb control group and 68.97% in the western medicine control group (P < 0.01). CONCLUSION Compound Polygonum multiflorum extract has effect on AD, and it is superior to Polygonum multiflorum extractor Naofukang.
-
6.
Weight loss, nutritional status and physical activity in patients with Alzheimer's disease. A controlled study.
Wang, PN, Yang, CL, Lin, KN, Chen, WT, Chwang, LC, Liu, HC
Journal of neurology. 2004;(3):314-20
Abstract
The etiology of weight loss in Alzheimer's disease (AD) patients is still uncertain. This study was designed to investigate the possible factors that might contribute to weight change of AD patients. From July 1999 to June 2001, we recruited 51 AD patients and 27 non-demented controls. Demographic data, neuropsychological tests, Geriatric Depression Scale-Short Form, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. More than half of our AD patients developed body weight loss, and overall, the AD patients were significantly thinner than the non-demented subjects. Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients. The AD patients had fewer daily physical activities. More AD patients had the problem of poor appetite. However, daily calorie intake was not significantly different between the two groups. The AD patients, especially those who presented with body weight loss, even consumed more calories per body weight kilogram (kg) per day. In the food composition analysis, AD patients took more carbohydrate than controls. Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss. We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients, and that these changes contribute to the weight loss.
-
7.
Folic acid supplementation in dementia: a preliminary report.
Sommer, BR, Hoff, AL, Costa, M
Journal of geriatric psychiatry and neurology. 2003;(3):156-9
Abstract
Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia.
-
8.
Reduced glutamate neurotransmission in patients with Alzheimer's disease -- an in vivo (13)C magnetic resonance spectroscopy study.
Lin, AP, Shic, F, Enriquez, C, Ross, BD
Magma (New York, N.Y.). 2003;(1):29-42
Abstract
Cognitive impairment in Alzheimer's disease (AD) is not fully explained. PET indicates reduced cerebral metabolic rate for glucose. Since glutamate neurotransmission (GNT) consumes more than 80% of the ATP generated from metabolism, a pilot study was carried out to determine the neuronal tricarboxylic acid cycle (TCA) based on the hypothesis that reduced GNT could contribute to cognitive impairment in AD. Three AD patients with cognitive impairment (mini-mental state exam: 24 vs 30, P<0.05) and significant reduction in both N-acetyl aspartate (NAA)/Creatine (Cr) ( P<0.009) and NAA/myo-inositol (mI) ratio ( P<0.01), and three age-matched controls each received 0.014-0.016 g/kg/min 99%1-13C glucose IV. Quantitative (1)H and proton-decoupled (13)C MR brain spectra were acquired from combined posterior-parietal white matter and posterior-cingulate gray matter every 5 min for 140 min.(13)C magnetic resonance spectroscopy (MRS) measures of glucose oxidation and neuronal TCA rate, including prolonged time to (13)C enrichment of glutamate (Glu2) ( P<0.004) and bicarbonate (HCO(3)) ( P<0.03) as well as reduced relative enrichment of Glu(2)/Glu(4) between 60 and 100 min ( P<0.04), were significantly different in AD patients vs. controls. (13)C measures of GNT, glutamine (Gln)(2)/Glu(2) ( P<0.02) and rates of glutamate enrichment (Glu(2)/glucose: 0.34 vs 0.86, P=ns and Glu(4)/glucose 0.26 vs 0.83, P=ns), were also reduced.(13)C MRS measures of neuronal TCA cycle, glucose oxidation and GNT were significantly correlated with measures of neuronal integrity: NAA/Cr, [NAA] and mI/NAA as determined by (1)H MRS ( R(2)=0.73-0.95; P<0.05-0.01), suggesting that impairment of GNT may be a contributing factor in the cognitive impairment characteristic of AD.
-
9.
Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin.
Muresanu, DF, Rainer, M, Moessler, H
Journal of neural transmission. Supplementum. 2002;(62):277-85
Abstract
BACKGROUND Cerebrolysin (Cere) is a peptidergic, neurotrophic drug which has been shown to improve cognitive performance and global function of Alzheimer's disease (AD) patients in earlier trials. In this study, we have attempted to replicate this findings with particular emphasis on functional improvement of the patients. PATIENTS AND METHODS Patients received infusions of 30 ml Cere or placebo five days/week for six consecutive weeks. Patients had to have a diagnosis of AD and a MMSE score of 14-25 inclusive. Effects on cognition, global function, and activities of daily living were evaluated 3, 6, and 18 weeks after the beginning of the infusions. RESULTS Significant improvement of cognitive function, clinical global impression and activities of daily living were seen after the end of the therapy. The effects were most pronounced in the DAD score, a measure for the capability to perform activities of daily living. Interestingly, and in line with the findings of earlier studies, the treatment effect of Cere was maintained after cessation of treatment up to the week 18 assessment. CONCLUSION The data confirm the findings of earlier trials and clearly demonstrates that Cere leads to functional improvement of patients with AD. The sustained treatment effect of Cere after withdrawal has been confirmed.
-
10.
Senile plaques do not induce susceptibility effects in T2*-weighted MR microscopic images.
Dhenain, M, Privat, N, Duyckaerts, C, Jacobs, RE
NMR in biomedicine. 2002;(3):197-203
Abstract
Senile plaques are the hallmarks of Alzheimer's disease. They typically range from 16 to 150 microm in size with most less than 25 microm. Mechanisms by which they might affect MR contrast and thus be made visible in this imaging modality are still unknown. Plausibility studies suggested that they might have a different magnetic susceptibility than surrounding tissue. A large difference would cause the plaque and a relatively large volume of adjacent tissue to be hypo-intense in T2*-weighted MRI scans, thus causing them to appear larger than their actual sizes and perhaps visible even when their size is below the nominal resolution limit of the imaging experiment. To evaluate this hypothesis, formalin-fixed superior temporal gyrus samples obtained from two Alzheimer's disease and two control subjects were imaged using magnetic resonance microscopy at 11.7 T. Three dimensional T2*-weighted gradient echo images were recorded with an isotropic resolution of 23.4 microm. The imaging protocol was especially sensitive to susceptibility effects. Samples were then stained for amyloid and/or iron deposits. Hypo- and hyper-intense structures were clearly visible in MR images from all samples. Hyper-intense structures reflected fixative penetration within the vascular system. Almost all the hypo-intense structures were blood vessels. Their hypo-intense profile was probably caused by iron deposits associated with the cell aggregates that they contained. Only one hypo-intense spot could be matched with a plaque and this was one of the largest plaques in our samples. The remainder of the several hundred plaques were not visible in MR images. In histological slices the senile plaques were often larger than small blood vessels that were visible in the MR images. This suggests that susceptibility effects are not associated with senile plaques and do not provide a mechanism to differentiate them from surrounding tissue.