Alzheimer's disease recognized as a progressive multifarious neurodegenerative disorder is the leading cause of dementia among older age people. From the last two decades, advancement in the field of pathogenesis has encouraged the researchers for the examination of novel pharmacological therapeutics of this disease. Though the neuro-pathological characteristics of Alzheimer's disease are perceived but the complexities of the mechanism have not been clearly defined. This gap of understanding is the reason for the non-availability of effective therapeutic treatment for this disease. In this review, we will discuss current attempts to formulate an extensive Alzheimer's disease pathogenesis theory and its management. A better understanding of the pathophysiology of this disease could inform and impact the future development of Alzheimer's disease directed treatment strategies.
Alzheimer's disease is a very common cause of dementia and responsible for 50% - 60% of all of the cases. It damages the brain cells and nerves disrupting the transmitters which carry information in the brain, especially those responsible for storing memories [1]. The brain shrinks as gaps develop in the temporal lobe and hippocampus. First, describe by Alois Alzheimer in 1906. In the case of Alzheimer's disease, it affects people's ability to remember, speak, think and make decisions. Certain chemicals production in the brain, such as acetylcholine is also affected by Alzheimer's disease. It is unknown till date that what causes nerve cells to destroy but there are some characteristic appearances of the brain after the death [2, 3]. 'Tangles' and 'Plaques' made from protein fragments are identified under the microscopic view in damaged areas of the brain. This approves the diagnosis of Alzheimer's disease [4]. Generally, it is determined in people over 65 years, whereas the less-prevalent early onset of Alzheimer’s can be identified much earlier. Around the world, there were 9.9 million new cases of dementia in 2015; it means one Alzheimer's disease case in every 3 seconds. During 2010, there are 3.7 million Indians identified with dementia and total societal costs were about 14,700 crore for the same [5, 6]. The world’s population is speedily aging, and the number of people affected with dementia is expected to grow from 35 million today to 65 million by the year 2030. The increasing population of India (the world’s 2nd largest) is facing a crisis among the elderly and infirm [7]. According to the Dementia India 2010 report, the number of persons with dementia and families affected by dementia is set to increase rapidly. Alzheimer's disease suppose to affect 1 in 85 people globally by 2050.
Stages of Alzheimer’s disease:
1) Mild/Early Stage (lasts 2-4 yrs): constant memory loss, especially of recent conversations and events. Repeat questions, problems in expressing and understanding the language. It is difficult to writing and using objects, depression and apathy can occur. Require reminders for daily activities and difficulties with sequencing impact driving early in this stage [8, 9].
2) Moderate/Middle Stage (lasts 2-10 yrs): This is considered as a middle/moderate stage and the duration is 2-10 years. Symptoms like unusual reasoning, confusion about current events, time, and places. Possible to become lost in familiar relationships, sleep disturbances, and mood or behavioural symptoms accelerate. About to 80% of patients exhibit the emotional and behavioural problems which are provoked by the stress and change. Require structure, reminders, and assistance with activities of daily life style.
3) Severe/Late Stage (lasts 1-3+ yrs): This is considered as the severe stage and the duration is 1-3 years. Symptoms like confused about past and present. Unable to the identity of familiar peoples and places and care by itself. Intense problems with mood, behavioural problems, hallucinations, and delirium. Patients require total support and care, and at last die from infections or pneumonia
Causes of Alzheimer: Alzheimer’s disease is progressive brain cell death that happens over a series of times. The brain size shrinks with Alzheimer's disease; the tissue has constantly fewer nerve cells and connections. Plaques are begins between the dying cells in the brain from the buildup of a protein called beta-amyloid. The tangles are in the brain neurons from a disintegration of another protein, called tau [10]. Alzheimer's disease develops because of a complex series of events that appear in the brain over a long period of time. It is expected that the causes include genetic profile, environmental, and lifestyle factors [11, 12].
Non modifiable factors
· Age
· Family history
· ApoE4 allele
· Female sex
· Depression
· Head trauma
· Mutation on 1, 14, 21 chromosome
· Down’s syndrome
Modifiable factors
· Vascular disease
· Hypertension
· Diabetes
· Dyslipidaemia
· Nutritional deficiency
· Smoking
· Alcohol
· Obesity
· Diet
Diagnosis of Alzheimer's disease: People affected with Alzheimer's disease diagnosed clinically based on the presence of neurological and neuropsychological features and from the patient history, relative’s collateral history, & clinical observations [13]. Advance medical visualization with computed tomography (CT) and with single photon-emission computer tomography (SPECT). The diagnosis can be confirmed with a very high truthfulness post-mortem report when brain material is available.
Treatment for Alzheimer's disease: Although there is currently no approach to cure Alzheimer's disease or stop its progression, scientists are encouraging advances in Alzheimer's disease treatment, including via medicines and non-drug approach to improve symptom management. In India, the family members are the caregiver for Alzheimer's disease patients. A majority lack the basic understanding of the condition, there are deficient information, awareness and special services for such patients and even for families [14, 15]. Sometimes, it may become hard to even diagnose because patients, and the families are not forthright and ill-informed. Researchers promote to search for ways to better treat Alzheimer's disease and other progressive dementias. There are some examples of medicines used to treat Alzheimer's disease and its Symptoms like Aricept (delay or slow the symptoms of Alzheimer's disease), Celexa (Used to reduce depression and anxiety), Depakote (Used to treat severe aggression), Remeron (Used to reduce depression and anxiety) [16]. Having support systems and the benefits of non-pharmacologic behavioral interventions can better the quality of life for both people with dementia and their family and family members, this includes:
· Treatment of co-existing medical situations
· coordination of treatment through the health care professionals
· Participation in liveliness, which can improve mood
· Behavioral interventions
· Education about the disease
· Building a care team for support
Modern Treatments for Alzheimer's disease:
· To stop the debilitating symptoms of Alzheimer's disease, a molecule called a beta-secretase inhibitor designed by the researcher’s team. It prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. It has been shown to be safe in its first phase of clinical trials and to reduce biomarkers for the disease.
· Researchers at Mount Sinai School of Medicine have found that a compound called NIC5-15 might be a safe and effective treatment of Alzheimer's disease [17].
· Mefenamic acid, a common Non-Steroidal Anti Inflammatory Drug, is commonly used for period pain, researchers said. For the study, researchers led by David Brough from Manchester University, used transgenic mice that developed symptoms of Alzheimer's disease.
· Common herbs such as Brahmi, Ashwagandha may be used to treat Alzheimer's disease through the science of Ayurveda.
Living with Alzheimer’s disease is a journey that changes gradually over time. There are many steps that both patients and caregivers can take to make this journey easier. Treatments are available today that can help improve the symptoms of Alzheimer's disease as well as some of the moods or behaviours that can result from Alzheimer's disease. Treatments work best when begun early. The earlier a person can be diagnosed, the better. New treatments for Alzheimer's disease, and new ways to diagnose it early, are also in development. Life with Alzheimer's disease still has its ups and downs. But it doesn’t need to be overwhelming. With the help of your neurologist and the support of friends and family, it is possible for both patients with Alzheimer’s and their caregivers to enjoy what life has to offer.