About Alzheimer's & Dementia
New treatment strategies
Music and memory program decreases the use of antipsychotic and anti-anxiety medications and improves dementia symptoms
A new study found personalized music and memory therapy helped decrease antipsychotic and anti-anxiety medication use, as well as improve dementia symptoms, in people living with Alzheimer’s disease (AD) and related dementias (ADRD).
“Results from this study offer the first evidence that the M&M [Music and Memory] individualized music program may be associated with reductions in antipsychotic and anxiolytic [to reduce anxiety] medication use as well as improvement in behavioral and psychological symptoms of dementia among nursing home residents with ADRD,” Kali Thomas, PhD, the lead researcher said.
To evaluate the benefits of M&M, researchers compared six-month outcomes in 12,905 long-term residents of 98 nursing homes that participated in the program, against the outcomes of 12,811 residents of another 98 facilities that did not participate in the program. They found that the proportion of residents who discontinued antipsychotic medications increased from 17.6% to 20.1% in care facilities that used personalized music while it remained stable in those facilities that did not use music.
A similar trend was observed in the use of anti-anxiety medications as well. The facilities using M & M program also report increased rate of reduction in behaviours (from 50.9% to 56.5% versus comparison facilities where the rate remained stable over a 6 month period.
Music and memory therapy was found to have the potential to replace the effects of antipsychotics and other psychoactive medications used to treat dementia, with the added benefit of not having secondary risks.
Source: Alzheimer's News Today
Researchers explore new ways to deliver memory loss treatment to the brain
A treatment that uses microscopic droplets of fat – called nanoliposomes – to carry drugs to the brain has been used effectively to target cancer cells. Now the technique has shown promise in restoring memory loss in mice models of Alzheimer’s disease, according to a new study funded by the Alzheimer’s Society.
The study, “Retro-Inverso Peptide Inhibitor Nanoparticles As Potent Inhibitors Of Aggregation Of The Alzheimer’s Aβ Peptide,” was published in the journal Nanomedicine: Nanotechnology, Biology and Medicine. The hallmark of Alzheimer’s disease is the toxic accumulation of the beta-amyloid protein, which blocks the proper functioning of neurons. This new treatment delivers nanoliposomes decorated with protein particles that can stop the accumulation of the beta-amyloid protein. The fat molecules that the nanoliposomes are made of fuse with the cell’s envelope, delivering the protein fragments into neurons.
Researchers observed that, even in low amounts, the protein particles rescued cultured neurons from the toxic effect of accumulated beta-amyloid. They also observed that injecting the nanoliposomes containing the protein fragments in mice with Alzheimer’s disease for three weeks provided protection against memory loss.
Source: Alzheimer’s News Today
Potential Alzheimer’s treatments in growing number of phase 2, and phase 3 trials
The number of clinical trials evaluating possible treatments for Alzheimer’s disease is on the increase, according to a recent analysis conducted by ResearchersAgainstAlzheimer’s(RA2), a global network of Alzheimer’s researchers that is part of a non-profit organization promoting the study and treatment of this disease, called UsAgainstAlzheimer’s.
The results were recently presented at this year’s UsAgainstAlzheimer’s National Alzheimer’s Summit, held in Washington’s, D.C., under the title “Where are We on the Path to 2025.” To date, there are 57 Phase 2 and 23 Phase 3 ongoing clinical trials to test potential Alzheimer’s medications, and 19 such drugs are estimated to come onto the market in the next five years. The analysis not only showed that the science behind Alzheimer’s is moving forward, but also that clinical trials are keeping up with drug development and research investigating new ways to combat the disease.
Alzheimer’s and Diabetes Exhibit Same Neuronal Damaging Process
Researchers at the Scintillon Institute for Biomedical and Bioenergy Research, San Diego, have discovered that the high blood sugar levels that mark type 2 diabetes and the plaque-forming β-amyloid protein found in Alzheimer’s disease (AD) cause the same alterations in several brain enzymes. The findings explain the association long observed between AD and diabetes.
Researchers found that both high blood sugar and Beta amyloid increase the level of nitric oxide and other free radicals. These free radicals induce some enzymatic changes- namely S-nitrosylation of multiple enzymes which in turn leads to decreased degradation and hence accumulation of insulin and beta amyloid. The enzymatic changes also damage neuronal connections called synapses in the brain. While both high blood sugar and Beta amyloid can independently cause damage to synaptic connections, the combination causes the greatest loss of neuronal connections. This explains why high blood sugar worsens memory loss in individuals with AD.
The findings also introduce a new risk for people with metabolic syndrome and known to be at risk for diabetes — the possible development of AD.
Source:Kegel, M. (2016, Jan. 12). Alzheimer’s and Diabetes Exhibit Same Neuronal Damaging Process. Alzheimer News Today. Retrieved from: http://alzheimersnewstoday.com/2016/01/12/link-between-alzheimers-disease-and-diabetes-discovered/
Trials of anti-amyloid vaccines and drugs
The human polyclonal IgG antibody preparation known as Intravenous Immunoglobulin (IVIG) has been under study as a potential treatment for Alzheimer's disease (AD) since 2002. In early stage AD clinical trials, IVIG was found to reduce cognitive decline and increase brain glucose metabolism. Unfortunately, IVIG failed to meet primary outcome objectives in the North American Phase 3 clinical trial in mild to moderate AD. However, biomarker studies revealed dose dependent increases in plasma and CSF immunoglobulins and decreases in beta amyloid-42 levels. In addition, IVIG treatment was generally safe and well-tolerated. These findings suggest that naturally occurring human anti-amyloid antibodies may play a physiologic role in the clearance of aggregated amyloid proteins.
Next generation of trials focuses on testing anti-beta amyloid vaccines in cognitively healthy people with PET scan evidence of senile plaques (A4 trial) and testing anti-beta amyloid vaccines or drugs in presymptomatic disease mutation carriers. Studies are also ongoing using BACE inhibitors in the above mentioned group of population.
Anti-depressant Citalopram shows promise as a future anti- amyloid agent
A single dose of the SSRI citalopram, marketed under the brand name Celexa, cut Aβ production by a third in the cerebrospinal fluid (CSF) of healthy volunteers. Future studies may reveal whether chronic dosing produces the same effect, and if this would lessen amyloid buildup in the brain. If there is a sustained benefit, then SSRIs may join immunotherapy and BACE inhibitors as another possible route to curb amyloid pathology. Many SSRIs have been approved by the FDA and they have acceptable safety profiles.
Other researchers called the findings promising, while noting that the road to a potential therapy remains long. The big question is, whether this can translate into a clinically preventative or therapeutic effect.
Source: An antidepressant decreases CSF Amyloid Beta production in healthy volunteers and in transgenic AD mice- by Sheline YI, West T, Yarasheki K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak MV, Chott R, Bateman RJ, Morris JC, Mintun MA, Lee JM, Cirrito JR, Sci Transl Med. 2014 May 14; 6(236) PubMed.
Corplex Donepezil skin patch therapy moves to phase 1 trial
A once-weekly transdermal patch delivers the most commonly prescribed treatment for Alzheimer’s disease in a way that is biologically equivalent to taking the medication orally, according to preliminary pilot study results.
Corium International conducted the bioequivalence (BE) pilot study on its lead product, Corplex, which delivers donepezil — the same active ingredient found in the orally administrated Aricept (donepezil hydrochloride) — through skin absorption. Corium’s Corplex system was designed to enable efficient delivery across the skin (transdermal) of small therapeutic molecules. These transdermal patches can adhere to either wet or dry surfaces for an extended period of time.
To confirm this new therapy could deliver the therapeutic active compound as efficiently as Aricept, the company conducted a BE pilot study where they tested two Corplex Donepezil transdermal patches that differed only in size. Patients treated with Corplex Donepezil presented similar concentrations of the drug in their blood as those reported in patients treated with Aricept. The smaller patch formulation achieved the FDA’s established endpoint.
With no significant skin safety or gastrointestinal side effects reported, the results indicated that Corplex Donepezil has a similar safety and drug delivery profile to Aricept. Notably, the incidence of nausea in patients treated with the smaller patch was more than four times lower than that reported for Aricept.
Source: Alzheimer's News Today, May 12 2017
Axsome’s therapy for agitation granted fast track designation by FDA
Axsome Therapeutics’ investigational drug AXS-05 was recently granted fast track designation by the U.S. Food and Drug Administration (FDA) for the treatment of agitation in patients with Alzheimer’s disease. The designation intends to speed up the development and regulatory handling of the drug, which is currently in the planning stage for a Phase 2/3 clinical trial.
“Agitation is reported in nearly half of individuals living with Alzheimer’s disease, results in distress to patients and caregivers, and has significant consequences, including early nursing home placement and increased mortality,” Herriot Tabuteau, MD, the CEO of Axsome, said in a press release. Symptoms come in the form of irritability, aggressive behaviors, emotional distress, and uninhibited behaviors.
The symptoms are also linked to lower functional capacity, increasing the burden on caregivers and often leading to earlier placement in a nursing home. Treatments aimed at specific symptoms that might improve the quality of life of patients are increasingly important, especially with the recent failings in the development of drugs to treat or prevent Alzheimer’s.
AXS-05 is a combination of the two drugs bupropion and dextromethorphan. Both have extensive actions on brain neurotransmission. In addition to these effects, bupropion also increases the concentration of dextromethorphan in the body after dosing.
Source: Alzheimer's News Today, May 10 2017
Transcranial magnetic stimulation for AD boasts clinical success in Phase 3 trials
In Alzheimer’s disease, synaptic activity goes haywire and brain networks gradually falter. This has made some researchers wonder if externally stimulating brain activity could help people with the disease function better for a while. The answer appears to be a tentative yes.
At the 13th International Conference on Alzheimer’s and Parkinson’s Diseases, held March 29 to April 2 in Vienna, Babak Tousi of the Cleveland Clinic Lou Ruvo Center for Brain Health in Lakewood, Ohio, reported positive results from a short Phase 3 trial of neuroAD, a therapy system developed by the Israeli medical technology company Neuronix. Classed as a medical device, neuroAD combines repetitive transcranial magnetic stimulation (rTMS) of several brain areas with cognitive training tailored to strengthen those same regions.
Participants with mild AD who received the intervention for six weeks maintained stable cognitive abilities six weeks later, whereas cognition continued to decline in those who received sham stimulation, Tousi said. Though the effects were small, they met prespecified outcomes and were consistent with previous reports of efficacy from smaller studies. The system is already approved for use with AD in Europe, and Neuronix is now applying for marketing clearance from the U.S. Food and Drug Administration.
The next step is to conduct more studies to come up with the right dose and to see how long the results are sustained.
Source: Alzheimer News Today
Latest clinical data on Namenda confirms beneficial effects for patients with Alzheimer’s Disease.
Results from four recent studies confirmed the beneficial clinical effects of Namenda (memantine), an FDA-approved Alzheimer’s therapy, to treat the disease’s behavioral and functional symptoms in people with moderate to severe disease.
Namenda blocks the activity of specific brain receptors that are believed to be associated with Alzheimer’s symptoms. Used to treat moderate to severe dementia, the drug is also suggested to have the potential to improve memory, awareness, and the ability to perform certain daily functions.
Detailed analysis of data pooled from three Phase 3 trials, which included data on 1,140 Alzheimer’s patients, showed that combined Aricept and Namenda therapy could reduce agitation and other behavioral problems. This effect was also found to be beneficial to caregivers, reducing their burden related to these Alzheimer’s symptoms.
Source: Alzheimers News Today