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A program of exercise, brain training, and lecture to prevent cognitive decline.
Kouzuki, M, Kato, T, Wada-Isoe, K, Takeda, S, Tamura, A, Takanashi, Y, Azumi, S, Kojima, Y, Maruyama, C, Hayashi, M, et al
Annals of clinical and translational neurology. 2020;(3):318-328
Abstract
OBJECTIVE We examined the benefits of a community-based program combining physical exercise, cognitive training, and education on dementia and lifestyle habits. METHODS This crossover open-label trial included 141 community-dwelling elderly people with suspected mild cognitive decline (MCD). Subjects were assigned to a 6-month intervention-first/6-month observation-second (INT-OBS) group or an OBS-INT group. The 6-month intervention consisted of 2 h of physical exercise, cognitive training, and classroom study or rest once weekly. Primary outcome was change in Touch Panel-type Dementia Assessment Scale (TDAS) score. RESULTS TDAS score improved significantly during the intervention period compared with the observation period for all subjects (P < 0.05). Some physical functions also improved significantly during the intervention period compared with the observation period in the OBS-INT group (P < 0.05). INTERPRETATION This community-based program improved both cognitive and physical function in elderly people with suspected MCD.
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Mid-life serum Vitamin D concentrations were associated with incident dementia but not late-life neuropsychological performance in the Atherosclerosis Risk in Communities (ARIC) Study.
Fashanu, OE, Zhao, D, Schneider, ALC, Rawlings, AM, Sharrett, AR, Lutsey, PL, Gottesman, RF, Gross, AL, Guallar, E, Alonso, A, et al
BMC neurology. 2019;(1):244
Abstract
BACKGROUND Activated Vitamin D has anti-inflammatory properties and adequate 25-hydroxyvitamin D [25(OH)D] concentrations may be important for neurocognitive function and protection against neurologic injury. We examined whether mid-life 25(OH) D concentrations were associated with later-life performance on neuropsychological testing, functional ability, depressive symptoms, and incident dementia. METHODS We studied 13,039 white and black ARIC participants who had serum 25(OH) D measured mid-life at visit 2 (1990-1992). Over the next ~ 20 years through visit 5 (2011-2013), participants underwent 3 additional in-person visits, annual telephone calls, and hospitalization surveillance. An extensive battery of neuropsychological outcomes were assessed at visit 5 using standardized protocols. Incident dementia was ascertained through a formal algorithm that included data from in-person cognitive testing, telephone interviews, hospital discharge codes, and death certificate codes. Diagnoses of dementia were adjudicated by expert clinician committee. For the primary cognitive analyses, we imputed for missing covariates and outcomes and used linear regression to evaluate non-concurrent cross-sectional associations of mid-life 25(OH) D (visit 2) with late-life neuropsychological outcomes (visit 5). We also used Cox regression models to examine associations of mid-life 25(OH) D and incident dementia. RESULTS In mid-life, the mean (SD) age of participants was 57 (6) years, 57% were women, and 24% black. Mean (SD) 25(OH) D was 24.3 (8.6) ng/mL; 33% had deficient (< 20 ng/mL), 44% intermediate (20- < 30 ng/mL), and 23% sufficient (≥30 ng/mL) 25(OH) D concentrations. Association between mid-life 25(OH) D and late-life performance on neuropsychological testing were mostly null. There was no significant association with functional ability or depressive symptoms. Results were similar in a sensitivity analysis using complete-case data (no imputation). However, after a median follow-up of 20 years, low 25(OH) D concentrations were associated with increased risk for incident dementia (p = 0.01 for trend across categories), with HR of 1.26 (95% CI 1.06, 1.49) for participants with deficient 25(OH) D, compared to sufficient concentrations. CONCLUSION In this community cohort, mid-life serum 25(OH) D concentrations were associated with incident dementia but not with performance on neuropsychological testing, functional ability, or depressive symptoms, 20 years later. Whether serum 25(OH) D concentrations are causally related to dementia or confounded by poorer health status remains uncertain. TRIAL REGISTRATION Registered on clinicaltrials.gov NCT00005131 .
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Sodium benzoate for the treatment of behavioral and psychological symptoms of dementia (BPSD): A randomized, double-blind, placebo-controlled, 6-week trial.
Lin, CH, Chen, PK, Wang, SH, Lane, HY
Journal of psychopharmacology (Oxford, England). 2019;(8):1030-1033
Abstract
OBJECTIVE Sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, improved cognitive function of early-phase Alzheimer's disease (AD) after 24-week treatment. This study examined benzoate treatment for behavioral and psychological symptoms of dementia (BPSD). METHODS In a double-blind, 6-week trial, 97 patients with BPSD were randomized to receive placebo or benzoate (mean dose: 622.0 mg/day). The primary outcomes were ADAS-cog and BEHAVE-AD. RESULTS Two treatments showed similar safety and primary and secondary outcomes. CONCLUSIONS Compared to antecedent 24-week, higher-dose treatment for early-phase AD, benzoate appeared ineffective in this 6-week trial. Longer-duration, higher-dose trials are warranted to clarify its efficacy for BPSD.
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Diagnostic impact of [18F]flutemetamol PET in early-onset dementia.
Zwan, MD, Bouwman, FH, Konijnenberg, E, van der Flier, WM, Lammertsma, AA, Verhey, FR, Aalten, P, van Berckel, BN, Scheltens, P
Alzheimer's research & therapy. 2017;(1):2
Abstract
BACKGROUND Early-onset dementia patients often present with atypical clinical symptoms, hampering an accurate clinical diagnosis. The purpose of the present study was to assess the diagnostic impact of the amyloid-positron emission tomography (PET) imaging agent [18F]flutemetamol in early-onset dementia patients, in terms of change in (confidence in) diagnosis and patient management plan. METHODS This prospective bi-center study included 211 patients suspected of early-onset dementia who visited a tertiary memory clinic. Patients were eligible with Mini Mental State Examination ≥ 18 and age at diagnosis ≤ 70 years and in whom the diagnostic confidence was <90% after routine diagnostic work-up. All patients underwent [18F]flutemetamol PET, which was interpreted as amyloid-negative or amyloid-positive based on visual rating. Before and after disclosing the PET results, we assessed the diagnostic confidence (using a visual analog scale of 0-100%) and clinical diagnosis. The impact of [18F]flutemetamol PET on the patient management plan was also evaluated. RESULTS [18F]flutemetamol PET scans were positive in 133 out of 211 (63%) patients, of whom 110 out of 144 (76%) patients had a pre-PET Alzheimer's disease (AD) diagnosis and 23 out of 67 (34%) patients had a non-AD diagnosis. After disclosure of PET results, 41/211 (19%) diagnoses changed. Overall, diagnostic confidence increased from 69 ± 12% to 88 ± 15% after disclosing PET results (P < 0.001; in 87% of patients). In 79 (37%) patients, PET results led to a change in patient management and predominantly the initiation of AD medication when PET showed evidence for amyloid pathology. CONCLUSIONS [18F]flutemetamol PET changed clinical diagnosis, increased overall diagnostic confidence, and altered the patient management plan. Our results suggest that amyloid PET may have added value over the standardized diagnostic work-up in early-onset dementia patients with uncertain clinical diagnosis. This study provides evidence for the recommendations put forward in the appropriate use criteria for amyloid PET in clinical practice. TRIAL REGISTRATION Nederlands Trial Register NTR3743 . Registered 7 December 2012.
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Effect of Rikkunshi-to on appetite loss found in elderly dementia patients: a preliminary study.
Utumi, Y, Iseki, E, Murayama, N, Nozawa, M, Kumagai, R, Matsubara, Y, Ichimiya, Y, Arai, H
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society. 2011;(1):34-9
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Abstract
BACKGROUND Functional gastrointestinal symptoms are frequently found in elderly dementia patients. In such a case, we attempt treatment by the administration of antidepressants or second-generation antipsychotics. However, these medications have a risk of side-effects. In the present study, we carried out oral administration of Rikkunshi-to to elderly dementia patients with appetite loss, and examined its effects on food intake. METHODS Six elderly dementia patients were recruited from inpatients. They showed appetite loss, but no organic abnormalities of the gastrointestinal organs. These patients were given Rikkunshi-to, at 7.5 g per day, t.i.d. for 4 weeks. We examined the food intake, weight, total protein, albumin and potassium in plasma before administration and for 4 weeks after administration. In statistical analyses, the percentage of food consumed for 4 weeks was analyzed by anova. We also examined the side-effects of Rikkunshi-to. RESULTS In patient 3, we stopped investigation after 3 weeks because of the development of cholecystitis. The values of 4 weeks in patient 3 were calculated as the mean values of 4 weeks in the other five patients. anova and Tukey's multiple comparison showed a marginally significant difference in weight between before Rikkunshi-to was given and 4 weeks after. In change of food intake, there were no significant differences between before Rikkunshi-to was given and 1 day after, 1 day and 2 days after, 2 days and 3 days after, 3 days and 1 week after, and 1 week and 2 weeks after; however, there were significant increases in food intake between other times. With regard to the side-effects, mild lower limb oedema appeared in the two patients. CONCLUSION In the present study, we showed the effect of Rikkunshi-to in improving appetite loss in elderly dementia patients. The present study suggests that Rikkunshi-to might be useful in improving functional appetite loss in elderly dementia patients, because there are no serious side-effects.
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Homocysteine but not neopterin declines in demented patients on B vitamins.
Frick, B, Gruber, B, Schroecksnadel, K, Leblhuber, F, Fuchs, D
Journal of neural transmission (Vienna, Austria : 1996). 2006;(11):1815-9
Abstract
Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Hyperhomocysteinemia is common in various forms of dementia, and a significant relationship was found between concentrations of homocysteine and immune activation marker neopterin. B vitamin supplementation is able to slow-down homocysteine formation in patients. In an open-label study, effects of B vitamin supplementation (Beneuran compositum ) on concentrations of homocysteine and neopterin were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16). In all groups of patients, a significant percentage of patients presented with homocysteine concentrations >15 micromol/L and with elevated concentrations of immune activation marker neopterin. Decline of homocysteine concentrations was observed after one month of B vitamin supplementation (all p<0.01; paired Kruskal-Wallisn-test). By contrast, neopterin concentrations remained unchanged (all p>0.05). B vitamin supplementation in patients with various forms of dementia did not influence neopterin concentrations, which indicates that the degree of immune activation and inflammation remained unchanged. The question remains, if lowering of homocysteine by folate supplementation alone could have any beneficial effect to modulate the course of dementia development and if longer period of supplementation would also ameliorate immune system activation status.
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[Effect of huannao yicong capsule on senile mild cognitive impairment].
Li, H, Liu, F, Xu, LR
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2004;(8):689-93
Abstract
OBJECTIVE To observe the effect of Huannao Yicong capsule (HYC) on senile mild cognitive impairment. METHODS Sixty-two patients were randomly divided into two groups, the 31 patients in the treated group were treated with HYC 3 capsules, 3 times daily, and the 31 in the control group with Hydergin 3 tablets, 3 times daily. Treatment for two successive months was a therapeutic course. The changes of cognitive effect index (CEI), integral of measuring scale (CCSE, FQA and MMSE), TCM Syndrome scoring, quality of life (QOL), cerebral arterial blood flow (CBF) and hemorrheologic parameters in the two groups were observed. RESULTS The total effective rate of treatment in improving cognition in the 30 patients of the treated group (with one case lost) was 83.33%, while that in the 29 patients of the control group (with two cases lost) was 48.28%, the difference between them was significant (u = 2.36, P < 0.05). Intent-to-treat analysis, namely, the case lost in the treated marked as ineffective and those in the control group as effective, showed the total effective rate in the two groups was 80.65% and 51.61% respectively, which also showed significant difference (u = 2.02, P < 0.05). In the treated group after treatment, the integrals of CCSE, FAQ and MMSE significantly increased (P < 0.05 or P < 0.01), the TCM Syndrome scoring decreased (P < 0.01), the scoring of QOL significantly improved, the mean BBF increased (P < 0.05 or P < 0.01), and the cerebral arterial resistance index improved significantly. All these improvements in the treated group were significantly higher than those in the control group respectively (P < 0.05). Besides, the hemorrheologic parameters in the treated group were improved, most of them were better than those in the control group (P < 0.05 or P < 0.01). CONCLUSION HYC has good therapeutic effect on senile mild cognitive impairment, it is safe without any adverse reaction.
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Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial.
Kanowski, S, Hoerr, R
Pharmacopsychiatry. 2003;(6):297-303
Abstract
In 1996, Kanowski et al. reported about the beneficial effects of ginkgo biloba special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) of mild to moderate severity. The comparison of the results of this double-blind, placebo-controlled, randomized, multi-center study with other dementia studies is hampered by the fact that only the responder analysis of the per-protocol (PP) population, which was pre-specified in the protocol as confirmatory analysis, has been published in detail so far. Moreover, cognitive functioning was measured using the Syndrom-Kurztest (SKT), whereas results of other studies are based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Therefore, the conventional intention-to-treat (ITT) analysis of this study is provided with an estimation of ADAS-cog scores based on measured SKT scores. After 24 weeks of treatment, the ITT analysis of the SKT and estimated ADAS-cog scores revealed a mean decrease in the total score by -2.1 (95 % CI: -2.7; -1.5) points and -2.7 (95 % CI: -3.5; -1.9) points, respectively, for the EGb 761 group, which indicates an improvement in cognitive function. On the contrary, the placebo group exhibited only a minimal change of -1.0 (95 % CI: -1.6; -0.3) and -1.3 (95 % CI: -2.0; -0.4) points, respectively. The changes from baseline differed significantly between treatment groups by 1.1 (SKT) and 1.4 (estimated ADAS-cog) points, respectively (P = 0.01). The Clinical Global Impression of Change (CGI, Item 2) favored the EGb 761 group with a mean difference of 0.4 points (P = 0.007). Changes in the rating related to activities of daily living (Nürnberger-Alters-Beobachtungs-Skala, NAB) showed a favorable trend for EGb 761R. A subgroup analysis regarding patients with DAT yielded comparable results. Using a decrease of at least 4 points on the estimated ADAS-cog scores as cutoff criterion for treatment response, 35 % of EGb 761-treated patients were considered responders versus only 19 % for the placebo group (P = 0.01). The results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementia. The therapeutic effect is in line with the outcome of another EGb 761 study conducted in the U.S.
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Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial.
van Dongen, M, van Rossum, E, Kessels, A, Sielhorst, H, Knipschild, P
Journal of clinical epidemiology. 2003;(4):367-76
Abstract
Preparations based on special extracts of the Ginkgo biloba tree are popular in various European countries. Previous studies have suggested the clinical efficacy of Ginkgo in patients with dementia, cerebral insufficiency, or related cognitive decline. However, most of these studies did not fulfill the current methodologic requirements. We assessed the efficacy of the G. biloba special extract EGb 761 in patients with dementia and age-associated memory impairment in relation to dose and duration of treatment. Our study was a 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Study participants were elderly patients with dementia (Alzheimer disease or vascular dementia) or age-associated memory impairment (AAMI). A total of 214 participants, recruited from 39 homes for the elderly in the Netherlands, were randomly allocated to Ginkgo (either 240 mg/d or 160 mg/d) or placebo (0 mg/d). After 12 weeks, the subjects in the two Ginkgo groups were randomized to continued Ginkgo treatment or placebo treatment. Primary outcome measures in this study were the Syndrome Kurz Test (SKT; psychometric functioning), the Clinical Global Impression of change (CGI-2; psychopathology, assessed by nursing staff), and the Nuremberg Gerontopsychological Rating Scale for Activities of Daily Living (NAI-NAA; behavioral functioning). One hundred twenty-three patients received Ginkgo (n=79, 240 and 160 mg/d combined) or placebo (n=44) during the 24-week intervention period. We found no statistically significant differences in mean change of scores between Ginkgo and placebo. The differences were SKT: +0.4 (90% confidence interval [CI] -0.9-1.7); CGI-2: +0.1 (90% CI -0.3-0.4), and NAI-NAA: -0.4 (90% CI -1.9-1.2). A positive difference is in favor of Ginkgo. Neither the dementia subgroup (n=36) nor the AAMI subgroup (n=87) experienced a significant effect of Ginkgo treatment. There was no dose-effect relationship and no effect of prolonged Ginkgo treatment. The trial results do not support the view that Ginkgo is beneficial for patients with dementia or age-associated memory impairment.
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Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia.
Clarke, R, Harrison, G, Richards, S, ,
Journal of internal medicine. 2003;(1):67-75
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OBJECTIVES To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia. SUBJECTS People with dementia or mild cognitive impairment. DESIGN AND INTERVENTION In a 2 x 2 x 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment. MAIN OUTCOME MEASURES At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B2) and reactive oxygen species (8-epi-PGF2 alpha). RESULTS Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected. CONCLUSIONS Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.