scholarly journals Neuromodulation for Apathy in Alzheimer’s Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study

2020 ◽  
Vol 77 (4) ◽  
pp. 1483-1493
Author(s):  
Prasad R. Padala ◽  
Eugenia M. Boozer ◽  
Shelly Y. Lensing ◽  
Christopher M. Parkes ◽  
Cassandra R. Hunter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Primary Objective ◽  
Secondary Outcome ◽  
Rapid Progression ◽  
Double Blind ◽  
Sham Treatment ◽  
State Examination

Background: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer’s disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. Objective: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. Methods: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. Results: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (–10.1 (–15.9 to –4.3); t (16)  = –3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15)  = 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16)  = 3.29; p = 0.005), and CGI-I (–2.56 (–3.5 to –1.6), t (17)  = –5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. Conclusion: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.

scholarly journals Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial

2021 ◽  
pp. 1-8
Author(s):  
M.M. Gonzales ◽  
V.R. Garbarino ◽  
E. Marques Zilli ◽  
R.C. Petersen ◽  
J.L. Kirkland ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Early Stage ◽  
Primary Objective ◽  
Secondary Outcome ◽  
Protein Accumulation ◽  
Open Label ◽  
Double Blind ◽  
Organ Systems

Preclinical studies indicate an age-associated accumulation of senescent cells across multiple organ systems. Emerging evidence suggests that tau protein accumulation, which closely correlates with cognitive decline in Alzheimer’s disease and other tauopathies, drives cellular senescence in the brain. Pharmacologically clearing senescent cells in mouse models of tauopathy reduced brain pathogenesis. Compared to vehicle treated mice, intermittent senolytic administration reduced tau accumulation and neuroinflammation, preserved neuronal and synaptic density, restored aberrant cerebral blood flow, and reduced ventricular enlargement. Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated conditions. With these data, we proposed and herein describe the objectives and methods for a clinical vanguard study. This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage Alzheimer’s disease. The primary objective is to evaluate the central nervous system penetration of dasatinib and quercetin through analysis of cerebrospinal fluid collected at baseline and after 12 weeks of treatment. Further, through a series of secondary outcome measures to assess target engagement of the senolytic compounds and Alzheimer’s disease-relevant cognitive, functional, and physical outcomes, we will collect preliminary data on safety, feasibility, and efficacy. The results of this study will be used to inform the development of a randomized, double-blind, placebo-controlled multicenter phase II trial to further explore of the safety, feasibility, and efficacy of senolytics for modulating the progression of Alzheimer’s disease. Clinicaltrials.gov registration number and date: NCT04063124 (08/21/2019).

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

scholarly journals Assessing the Progression of Alzheimer’s Disease in Real-World Settings in Three European Countries

2021 ◽  
Vol 80 (2) ◽  
pp. 749-759
Author(s):  
Albert Lladó ◽  
Lutz Froelich ◽  
Rezaul K. Khandker ◽  
Montserrat Roset ◽  
Christopher M. Black ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mixed Model ◽  
Primary Objective ◽  
Community Dwelling ◽  
Behavioral Changes ◽  
The Uk ◽  
State Examination ◽  
Study Inclusion

Background: There exists considerable variation in disease progression rates among patients with Alzheimer’s disease (AD). Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. Results: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, ‘not reached’) years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. Conclusion: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.

Mirtazapine does not improve sleep disorders in Alzheimer's disease: results from a double-blind, placebo-controlled pilot study

2016 ◽  
Vol 17 (2) ◽  
pp. 89-96 ◽  
Author(s):  
Francisca M. Scoralick ◽  
Luciana L. Louzada ◽  
Juliana L. Quintas ◽  
Janeth O.S. Naves ◽  
Einstein F. Camargos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Sleep Disorders ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals RE-PERG in early-onset Alzheimer’s disease: A double-blind, electrophysiological pilot study

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0236568
Author(s):  
Alberto Mavilio ◽  
Dario Sisto ◽  
Florenza Prete ◽  
Viviana Guadalupi ◽  
Rosanna Dammacco ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Early Onset ◽  
Double Blind ◽  
Early Onset Alzheimer’S Disease

P2-408: A double-blind, placebo-controlled, 18-month pilot study of the PPAR-gamma agonist pioglitazone in Alzheimer's disease

2006 ◽  
Vol 2 ◽  
pp. S366-S366 ◽  
Author(s):  
David S. Geldmacher ◽  
Thomas Fritsch ◽  
McKee J. McClendon ◽  
Alan J. Lerner ◽  
Gary E. Landreth
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Ppar Gamma ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Ppar Gamma Agonist

scholarly journals Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Letizia Leocani ◽  
Gloria Dalla Costa ◽  
Elisabetta Coppi ◽  
Roberto Santangelo ◽  
Marco Pisa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcranial Magnetic Stimulation ◽  
Cognitive Rehabilitation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Study ◽  
Transient Effects ◽  
Double Blind ◽  
Over Time

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of −1.01 points at the ADAS-Cog scale score per time point (95% CIs −0.02 to −3.13, p &lt; 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04562506.

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