This essay was submitted by Eva Sharma for the 2019 NxG Science Communicator Competition.
Today, dementia is increasingly being recognized as one of the most important medical problems in older people and Alzheimer’s disease is the most common form of dementia (60% – 80%). This has led to an enormous increase in research related to the disease. Despite all the efforts, at the moment there are very few effective therapeutic options for prevention and treatment of Alzheimer’s disease. It can be a public health crisis as the continuing increase in life expectancy has led to more people being diagnosed with Alzheimer’s. It has been estimated that 47 million people live with Alzheimer’s disease (AD) and other forms of dementia worldwide.
What is Alzheimer’s disease (AD)?
Alzheimer’s is a disease that slowly and progressively destroys the brain. Alzheimer’s disease was first described by Dr. Alois Alzheimer in 1906 during autopsy on the brain of a 55-year-old woman. An Alzheimer’s patient mainly suffers from dementia which includes memory loss, confusion, difficulty problem-solving, ability to perform everyday activities like reading, writing, speaking, planning etc. Alzheimer’s disease typically has three general stages -mild, moderate and severe. It is a complex disease because it can be influenced by a range of genetic and environmental factors. Genetic causes involve amyloid precursor protein (APP), presenilin-1(PS-1) and presenilin-2(PS-2) genes. The e4 form of the apolipoprotein E gene increases the risk of developing Alzheimer’s. Research and studies over the years have shown that the chances of having Alzheimer’s can be attributed to lifestyle as well. These risks are obesity, diabetes, heart problems, smoking, alcohol, aging and brain injuries.
Progress in tackling the disease
Initially, researchers found that the levels of neurotransmitter-acetylcholine are much lower in the brains of patients with Alzheimer’s. Drugs-Donepezil, Rivastigmine, and Galantamine were approved as they inhibit enzymes that destroy acetylcholine. Another approved drug-Memantine works by regulating a substance called glutamate, as excess amounts of glutamate can kill nerve cells. After this, the “amyloid cascade hypothesis” was accepted which states that AD results from accumulation of amyloid plaques collected between neurons which then disrupts cell function. The beta-amyloid protein is made from the amyloid precursor protein (APP) through splitting of protein. This has driven research into studying compounds that could prevent splitting and accumulation. The “tau hypothesis” proposes that tangles form in the brain, made from a protein called tau, which kills nerve cells.
Combination therapy uses a combination of different drugs which targets multiple pathogenic pathways to slow down the progression of Alzheimer’s. Monoclonal antibodies which involve laboratory produced antibodies that imitate immune response are used. Roche (Pharmaceutical Company) right now has two stage 3 projects. One is crenezumab and the other is gantenerumab, both focusing on beta-amyloid with monoclonal antibodies. A medication called BAN2401 has been found to lessen amyloid in the brain of 81% of patients and moderate cognitive decrease in the brain of 30%. A cholesterol control drug, Gemfibrozil, has been found to reduce amyloid levels and brain inflammation in mice. In Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), therapy in people with genetic risk of AD was designed to help remove excess beta-amyloid in the brain. The Alzheimer’s Prevention Initiative (API) tests therapies in people who have a high risk for Alzheimer’s but are without symptoms.
Some treatments have been unsuccessful in showing results while dozens are undergoing clinical trials. Neuropsychological tests were developed to evaluate decreased intellectual ability. Brain imaging using CT scans or MRI is used to indicate a reduction in the size of the brain. PET scans measure amyloid plaques and tau proteins in the brain. Patients also suffer from common behavioural symptoms like sleeplessness, agitation, anxiety, aggression and depression. These are managed by drugs like antidepressants and antipsychotics. Non-pharmacological therapies are often used for maintaining the cognitive abilities. Studies suggest that being socially and mentally active throughout life can possibly reduce the risk of Alzheimer’s. For example, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), found that lifestyle and vascular risk factors together led to beneficial effects in elderly individuals at a high risk for cognitive decline.
My vision towards progress
With a higher number of associations spreading awareness, Alzheimer’s disease has now become a global priority. There is still a large part of the older population not being diagnosed due to negligence because we may see symptoms of dementia as a part of the normal ageing process. Care is provided by family but there is an increase in trained caregivers. Caregivers are provided with skills and resources to continue helping patients. There will be a need for greater understanding of disease development before focusing on the making of drugs as different sources of the disease are coming forward. Alzheimer’s disease is thought to begin years before symptoms arise. Therefore, there will be more research done in understanding how various treatments are applicable to different stages of the disease. There will be more attention towards discovering biomarkers in the brain for better diagnosis of the disease. Biomarkers also will be critical to keep an eye on the effects of treatment. Many drugs for Alzheimer’s have entered Phase 3 trials meaning there will be more options of drugs in the market. Currently there are no treatments that can reverse the memory loss associated with Alzheimer’s disease so there will be more focus on improving behavioural symptoms and promoting a healthy lifestyle to prevent the disease. The main emphasis in the future will be towards the diagnosis, prevention, treatments, providing quality social life to the patients and family caregivers.
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