A LITERATURE REVIEW OF METHODOLOGIES USED IN RANDOMIZED CLINICAL TRIALS OF AGITATION IN ALZHEIMER’S DISEASE

2018 ◽  
pp. 1-14
Author(s):  
S. Dubé ◽  
J.T. Megerian ◽  
R. Malamut
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Literature Review ◽  
Randomized Clinical Trials ◽  
Cognitive Status ◽  
Pharmacological Intervention ◽  
Significant Heterogeneity ◽  
Open Label ◽  
End Points

Agitation is a common and burdensome symptom associated with Alzheimer’s disease (AD). This is a narrative literature review of the designs and methods used in randomized clinical trials of agitation in patients with AD; sources range from published, to completed but not published, to ongoing studies in the past 10 years. Selection for review included blinded, randomized trials conducted to assess the effect of a pharmacological intervention for which agitation in patients with AD was among the prespecified end points. Key criteria for exclusion included open-label studies, trials of dementia not specific to AD, or mixed populations of AD and unspecified dementia. A search of PubMed and clinicaltrials.gov databases identified 36 trials for which agitation was among the prespecified end points: 18 were published trials and 18 were completed but not published or ongoing. There was significant heterogeneity among AD studies in terms of diagnostic criteria, assessment of severity of disease and agitation, sample size and powering assumptions, treatment duration, patient age and cognitive status, and outcomes measurements. Few studies used a mitigation strategy for placebo response. Accumulating evidence suggests that it is important to consider the following in trial design: thresholds for baseline severity of agitation and AD; use of prespecified accepted criteria to define agitation; and use of standardized, validated tools to measure treatment effects during a trial. Adoption of these design strategies might help improve signal detection and bring us closer to identifying the most appropriate, effective, and safe treatments for agitation in patients with AD.

Dance for People with Alzheimer’s Disease: A Systematic Review

2019 ◽  
Vol 16 (10) ◽  
pp. 919-933 ◽  
Author(s):  
Alicia Ruiz-Muelle ◽  
María Mar López-Rodríguez
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Dance Therapy ◽  
Randomized Clinical Trials ◽  
Future Research

Background: In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews regarding the effect of this therapy exclusively on patients diagnosed with Alzheimer’s disease have not been found. Objective: The purpose of this study is to review the available literature describing clinical trials which explore the effects of dancing on psychological and physical outcomes, functionality, cognitive function, and quality of life in patients diagnosed with Alzheimer’s disease. In addition, this review aims to assess the quality of studies that perform dance therapy interventions in these patients. Methods: This study is a systematic review of randomized and non-randomized clinical trials regarding the effect of intervention including a dancing activity in people diagnosed with Alzheimer's disease. Results: In total, the evidence for this review rests on 12 studies with a total of 349 participants. The findings of this mini-review confirm the positive effect of dance therapy on physical and cognitive function, functionality, psychological outcomes, and quality of life in people with Alzheimer's disease. Conclusion: Most of the studies implementing dance as part of the therapeutic treatment has shown to improve or slow the worsening in the quality of life of patients with Alzheimer's disease and their caregivers. Future research focused on these patients should use a more exhaustive methodology and make a more detailed description of these kind of interventions.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of Low–Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3678 ◽  
Author(s):  
Sujin Kim ◽  
Yunkwon Nam ◽  
Chanyang Kim ◽  
Hyewon Lee ◽  
Seojin Hong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Ionizing Radiation ◽  
Pharmacological Intervention ◽  
Therapeutic Effects ◽  
Moderate Dose ◽  
Short Term ◽  
Anti Inflammatory ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects.

BACE1: a key regulator in Alzheimer’s disease progression and current development of its inhibitors

2021 ◽  
Vol 19 ◽  
Author(s):  
Smith Patel ◽  
Ankush Vardhaman Bansoad ◽  
Rakesh Singh ◽  
Gopal L. Khatik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Status ◽  
Current Development ◽  
Quality Work ◽  
Rate Limiting Step ◽  
Disease Modifying Treatment ◽  
Rate Limiting

Background: Alzheimer’s disease (AD) is a chronic neurodegenerative disease where no specific disease-modifying treatment is currently available. β-secretase (BACE1) is considered the potential and rationale target because it is involved in the rate-limiting step, which produces toxic Aβ42 peptides leading to deposits in the form of amyloid plaques extracellularly leading to AD. Objective: The role and implications of BACE1 and its inhibitors in the management of AD are discussed. Methods: We have searched and collected the relevant quality work from PubMed using the following keywords “BACE1”, BACE2”, “inhibitors”, and “Alzheimer’s disease”. In addition, we included the work which discusses the role of BACE1 in AD and the recent work on its inhibitors. Results: In this review, we have discussed the importance of BACE1 in regulating AD progression and the current development of BACE1 inhibitors. However, the development of a BACE1 inhibitor is very challenging due to the large active site of BACE1. Nevertheless, some of the BACE1 inhibitors have managed to enter advanced phases of clinical trials, such as MK-8931 (Verubecestat), E2609 (Elenbecestat), AZD3293 (Lanabecestat), and JNJ-54861911 (Atabecestat). This review also sheds light on the prospect of BACE1 inhibitors as the most effective therapeutic approach in delaying or preventing AD progression. Conclusion: BACE1 is involved in the progression of AD. The current ongoing or failed clinical trials may help understand the role of BACE1 inhibition in regulating the Aβ load and cognitive status of AD patients.

scholarly journals Physical therapy in patients with Alzheimer’s disease: a systematic review of randomized controlled clinical trials

2019 ◽  
Vol 26 (3) ◽  
pp. 311-321 ◽  
Author(s):  
Carlos Leonardo Sacomani Marques ◽  
Maria Helena Borgato ◽  
Eduardo de Moura Neto ◽  
Rodrigo Bazan ◽  
Gustavo José Luvizutto
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Physical Therapy ◽  
Functional Capacity ◽  
Randomized Clinical Trials ◽  
Disease Assessment ◽  
Clock Drawing Test ◽  
Significant Difference

ABSTRACT The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer’s Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer’s Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence.

Adults with Down syndrome in randomized clinical trials targeting prevention of Alzheimer's disease

2021 ◽  
Author(s):  
Wayne Silverman ◽  
Sharon J. Krinsky‐McHale ◽  
Warren B. Zigman ◽  
Nicole Schupf ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Down Syndrome ◽  
Randomized Clinical Trials
Sign in / Sign up

Export Citation Format

Share Document