Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

ObjectiveOur study aimed to assess the effect of a 12-month vitamin D supplementation on cognitive function and amyloid beta (Aβ)-related biomarkers in subjects with Alzheimer’s disease (AD).Methods This was a randomised, double-blind, placebo-controlled trial. 210 AD patients were randomly divided into intervention and control groups. Participants received 12-month 800 IU/day of vitamin D or starch granules as placebo. Tests of cognitive performance and Aβ-related biomarkers were measured at baseline, 6 months and 12 months.Results Repeated-measures analysis of variance showed significant improvements in plasma Aβ42, APP, BACE1, APPmRNA, BACE1mRNA (p<0.001) levels and information, arithmetic, digit span, vocabulary, block design and picture arrange scores (p<0.05) in the intervention group over the control group. According to mixed-model analysis, vitamin D group had significant increase in full scale IQ during follow-up period (p<0.001).ConclusionsDaily oral vitamin D supplementation (800 IU/day) for 12 months may improve cognitive function and decrease Aβ-related biomarkers in elderly patients with AD. Larger scale longer term randomised trials of vitamin D are needed.Trial registration numberChiCTR-IIR-16009549.

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Virtual Reality-Based Cognitive Stimulation on People with Mild to Moderate Dementia due to Alzheimer’s Disease: A Pilot Randomized Controlled Trial

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18105290 ◽

2021 ◽

Vol 18 (10) ◽

pp. 5290

Author(s):

Jorge Oliveira ◽

Pedro Gamito ◽

Teresa Souto ◽

Rita Conde ◽

Maria Ferreira ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Randomized Controlled Trial ◽

Virtual Reality ◽

Cognitive Function ◽

Controlled Trial ◽

Cognitive Stimulation ◽

Randomized Controlled ◽

Moderate Dementia ◽

Pilot Randomized Controlled Trial

The use of ecologically oriented approaches with virtual reality (VR) depicting instrumental activities of daily living (IADL) is a promising approach for interventions on acquired brain injuries. However, the results of such an approach on dementia caused by Alzheimer’s disease (AD) are still lacking. This research reports on a pilot randomized controlled trial that aimed to explore the effect of a cognitive stimulation reproducing several IADL in VR on people with mild-to-moderate dementia caused by AD. Patients were recruited from residential care homes of Santa Casa da Misericórdia da Amadora (SCMA), which is a relevant nonprofit social and healthcare provider in Portugal. This intervention lasted two months, with a total of 10 sessions (two sessions/week). A neuropsychological assessment was carried out at the baseline and follow-up using established neuropsychological instruments for assessing memory, attention, and executive functions. The sample consisted of 17 patients of both genders randomly assigned to the experimental and control groups. The preliminary results suggested an improvement in overall cognitive function in the experimental group, with an effect size corresponding to a large effect in global cognition, which suggests that this approach is effective for neurocognitive stimulation in older adults with dementia, contributing to maintaining cognitive function in AD.

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Brief psychotherapy in Alzheimer's disease

The British Journal of Psychiatry ◽

10.1192/bjp.187.2.143 ◽

2005 ◽

Vol 187 (2) ◽

pp. 143-147 ◽

Cited By ~ 40

Author(s):

Alistair Burns ◽

Else Guthrie ◽

Federica Marino-Francis ◽

Charlotte Busby ◽

Julie Morris ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Controlled Trial ◽

Well Being ◽

Good Evidence ◽

Psychotherapeutic Intervention ◽

Interpersonal Therapy ◽

Treatment As Usual ◽

Affective Symptoms

BackgroundAlthough there is good evidence that interventions for carers of people with Alzheimer's disease can reduce stress, no systematic studies have investigated psychotherapeutic intervention for patients themselves. This may be important in the earlier stages of Alzheimer's disease, where insight is often preserved.AimsThe aim was to assess, in a randomised controlled trial, whether psychotherapeutic intervention could benefit cognitive function, affective symptoms and global well-being.MethodIndividuals were randomised to receive six sessions of psychodynamic interpersonal therapy or treatment as usual; cognitive function, activities of daily living, a global measure of change, and carer stress and coping were assessed prior to and after the intervention.ResultsNo improvement was found on the majority of outcome measures. There was a suggestion that therapy had improved the carers' reactions to some of the symptoms.ConclusionsThere is no evidence to support the widespread introduction of brief psychotherapeutic approaches for those with Alzheimer's disease. However, the technique was acceptable and helpful individually.

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A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00795-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Shifu Xiao ◽

Piu Chan ◽

Tao Wang ◽

Zhen Hong ◽

Shuzhen Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trial ◽

Controlled Trial ◽

Drug Effects ◽

Disease Assessment ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer’s disease: a pilot randomized double-blind-controlled trial

International Psychogeriatrics ◽

10.1017/s1041610220003518 ◽

2020 ◽

pp. 1-13

Author(s):

Sanjeev Kumar ◽

Reza Zomorrodi ◽

Zaid Ghazala ◽

Michelle S. Goodman ◽

Daniel M. Blumberger ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Brain Plasticity ◽

Controlled Trial ◽

Memory Performance ◽

Double Blind ◽

Paired Associative Stimulation ◽

Post Hoc ◽

The Impact

ABSTRACT Design: Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation. Objectives: To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD). Methods: Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG. Results: There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling. Conclusions: This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

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A Randomized, Controlled Trial of Linopirdine in the Treatment of Alzheimer's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710002148x ◽

1997 ◽

Vol 24 (2) ◽

pp. 140-145 ◽

Cited By ~ 31

Author(s):

Kenneth Rockwood ◽

B. Lynn Beattie ◽

M. Robin Eastwood ◽

Howard Feldman ◽

Erich Mohr ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Controlled Trial ◽

Small Degree ◽

Disease Assessment ◽

Double Blind ◽

Cognitive Subscale ◽

Parallel Group ◽

Treatment Dose ◽

Age Range

ABSTRACT:Objectives:We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.Methods:A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.Results:No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.Conclusions:This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

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