Active clinical trials for "Alzheimer Disease"

In Alzheimer's disease (AD) an imbalance between the production and clearance of the ß-amyloid peptide is hypothesized as the driving event of the disease. The decreased clearance of Aß could be partly linked to a progressive dysfunction of the brain vasculature and of the blood brain barrier (BBB). Among many possible explanations for these failures of the multiple clinical trials evaluating innovative drugs in AD, one is the lack of target engagement, as none of these drugs is able to readily cross BBB. This barrier acts as a wall that actively and passively prevents the crossing of molecules between the blood and the brain parenchyma compartments. Only 0.3% of intravenously injected anti-Aß immunoglobulins reach the brain despite a half-life of 15-20 days. Low intensity Focal ultrasound associated to microbubble injection can open the BBB in a non invasive way. These openings are reversible in 2 hours to 2 days depending on the intensity of the ultrasound. Ultrasound opening of the BBB was initially used in a transgenic mouse model of AD to increase the brain delivery of an anti-Aß antibody. In this article, the Aß load was reduced in ultrasound treated brain region. Surprisingly it was then demonstrated that the simple opening of the BBB without any adjunct anti-Aß treatment was able to drive the same Aß clearance effects. This is probably linked to endogenous antibodies that are able to penetrate the brain parenchyma and target Aß plaques. Four opening sessions elicited positive promnesic effects in these mice. Our group conceived and developed a mean to easily, reproductively and innocuously open the BBB. A unique extra-dural ultrasound emitter (sonoCloud®) is surgically implanted in the skull under local anesthesia. It emits low intensity contact ultrasound (LICU) that are not deterred by bone and thus are able to open the BBB.Preclinical studies show the SonoCloud® device is safe and efficient as it allowed reproducible and repeatable opening of the BBB in rabbits, dogs and non human primates. Drugs up to 2000 Kilo Daltons (kDa) are able to cross the BBB to reach the brain parenchyma in which the concentration of Carboplatin was increased by 700% in the BBB opened region. No adverse event was evidenced both clinically, by EEG, Evoked potential, MRI, 18 Fluorodeoxyglucose (FDG) PET and histology in the primates after 7 bi-monthly sessions of LICU BBB opening. SonoCloud® and its external generator have been certified by the academic start-up CarThéra (APHP, UPMC). Our multidisciplinary skills (neurology, neurosurgery, neuroimaging, basic science departments in the same University hospital setting) and our previous experience of BBB opening in Man give us the unique opportunity to translate this procedure from neuro-oncology to AD which could 1) Have a positive effect on brain lesion load and symptoms by itself and 2) allow anti-AD (or more broadly, central nervous system) drugs to engage their targe

The aim of this study is to evaluate the effect of a 3-month walking program on brain energy metabolism in patient with mild Alzheimer's disease (AD). Two groups of sedentary patients with mild AD are followed and compared over a 3-month period of time: Control (non-active) and walking (from 15 to 45 minutes of exercise on a treadmill, 3 times a week for 12 weeks) groups. All the participants are evaluated on their cognition, brain volumes (MRI) and brain fuel consumption (PET scan with 18-FDG and 11C-AcAc) at the beginning and at the end of the study.

This study evaluates the safety and efficacy of AADvac1 in the treatment of patients with mild Alzheimer's disease. 60% of participants will receive AADvac1 and 40% of participants will receive placebo.

An experimental study designed to test the effectiveness of a psychological intervention based on group therapy for the caregivers of Alzheimer's disease patients. The intervention consists of 16 sessions of a cognitive-behavioral psychological group therapy. This study aims to demonstrate that Alzheimer's patients' caregivers can decrease the feelings of burden after been involved in a group therapy.

This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage.

Alzheimer's disease (AD) is commonly associated with behavioural changes such as agitation. Severe agitation is important to treat because it not only increases progression of AD and physical health problems (increased falls and weight loss), but it also decreases quality of life and increases caregiver stress. Currently prescribed treatments (i.e., antipsychotics) for agitation in AD do not work in everybody and when they do work the effect is small and they increase the risk of harmful side effects, including death. As a result, there is an urgent need for safer medication options. The cannabinoid nabilone can now be prescribed in capsule form for appetite and pain killing effects. Nabilone's calming effects may benefit those with agitation, and help the weight loss and untreated pain frequently associated with agitation. Through a clinical trial, the investigators hope identify the benefits of nabilone in the treatment of agitation in AD. The investigators objective is to determine whether nabilone is an efficacious and safe treatment for agitation, as well as having benefits for pain, weight and behavioural symptoms. This will be a 14 week clinical trial (participants take nabilone for 6 weeks, placebo for 6 weeks (order randomized) with 1 week between treatments). The investigators will assess and compare agitation, weight, pain, memory, behaviour and safety. Nabilone is a new class of medication that may be a safe and effective treatment for agitation in AD, with added benefits on appetite and pain. Reducing these symptoms would increase quality-of-life and reduce caregiver stress.

Rivastigmine, an acetylcholinesterase inhibitor which has been approved by FDA & HSA, is authorized for use in the treatment of mild to moderate dementia of the Alzheimer's type. In this trial, the investigators will be studying the effectiveness of Rivastigmine in subjects with AD and cerebrovascular disease.

This randomized controlled trial (RCT) will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention on cognition and hippocampal volume in AD with three aims: Determine the immediate effect of the cycling intervention on cognition in AD. Examine if the cycling intervention slows cognitive decline in AD from baseline to 12 months. Assess the effect of aerobic exercise on hippocampal volume in AD over 12 months using MRI. The investigators will randomize 90 participants to the 6-month cycling or stretching/range of motion exercise (20-50-minute, 3 times a week). Participants will then be followed for another 6 months. Cognition will be assessed at baseline, 3, 6, 9, and 12 months and hippocampal volume will be measured using magnetic resonance imaging (MRI) at baseline, 6, and 12 months.

To establish efficacy of idalopirdine as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-to-moderate Alzheimer's disease (AD).

Remembering how to travel from one location to another is critical in everyday life, yet this vital ability declines with normal aging and can be further affected by conditions that disproportionately affect the elderly, such as vision loss or progressive dementia. Human and animal research has shown that two distinct memory systems interact during navigation. The first, referred to as allocentric navigation, is very flexible and uses spatial knowledge of key features or landmarks to develop and use a mental map of the environment. This approach involves brain regions that are critical for new learning and memory but that decline with age. The second, referred to as egocentric navigation, is inflexible and relies on "habit" memories that link specific features with specific directions. This approach relies on brain regions that are critical for "automatic" responses and that are relatively unaffected by age. The main problem is that allocentric navigation declines with age and is accompanied increased dependence on egocentric navigation. This change increases the risk of becoming disoriented or "lost" when traveling in unfamiliar areas or even when traveling new routes in familiar areas. Therefore, the main goal of this project is to examine whether non-invasive brain stimulation, specifically transcranial direct current stimulation, can improve allocentric navigation in healthy older adults and patients with mild cognitive impairment. Participants will complete two functional magnetic resonance imaging sessions while learning new environments. Before one of these sessions, participants will receive active brain stimulation over the parietal cortex. Before the other session, participants will receive sham brain stimulation over the parietal cortex. The effects of this stimulation will be evaluated using both an allocentric and an egocentric memory test. Physiologic effects will be evaluated using both task-based and resting-state MRI.