Alzheimer's Clinical Trials

Alzheimer’s disease (AD) is a type of chronic neurodegenerative disorder that normally starts slowly and progresses over time, first affecting the overall mental health of an individual followed by gradually worsening physical symptoms. The cause is poorly understood, however could be due to several genetic and environmental factors.

It affects about 6% of people 65 or older, although 4-5% of cases are ‘early-onset’. Around 5.5 million people above 65 years old are affected by Alzheimer across the globe and around 200,000 others below the age of 65 are also affected by this disease [6]. Since AD shows a great impact on the mental abilities of an individual, it results in a significant decline on the overall lifestyle of this individual, to the point where they must usually be cared for by others as they can no complete basic tasks on their own.

Alzheimer’s disease is always associated with amyloid plaques and neurofibrillary tangles that could result in neuronal loss. AD is responsible for damaging synapses and neurons, which could cause cognitive-related symptoms. The e4 allele gene for apolipoprotein E (ApoE) could also be responsible for some of the function in the expression of Alzheimer's disease as it is seen in 60% of the affected individuals [3].

Beta amyloid is a fragment of a protein found in the brain. However, on a healthy brain these fragments are broken down and eliminated. AD decreases the capability of the brain to remove these protein fragments which could result in accumulation of insoluble plaques – which is proven to be toxic [4].

Neurofibrillary tangles are a complex network of fibers found in the brain cells, which consists of tau proteins. Those are a part of microtubules, who are responsible for the transport of nutrients across different nerve cells. A patient with Alzheimer has the microtubule's structure collapsed due to an abnormality in the tau protein. It should be noted that the number of neurofibrillary tangles shows a relationship with the degree of dementia [2].

Alzheimer's disease accounts for around 60% of dementia cases [4]. Dementia is a group of symptoms associated with memory loss and compromised thinking capability. Initially the symptoms include mild loss of memory with certain mental health issues. However, at later stages, the functions and structure of the brain desiccates to an extent that decreases the capability to perform many skills includes analyzing, decision making and performing familiar functions, such as difficulty speaking one's native language. It could also have adverse effects on mental health such as anxiety and depression. Those could result in personality changes as well as behavior changes of affected individuals. Other symptoms associated with AD may include hallucinations, agitation and delusion [1].

Supportive Care

Proper care can play a great role in the management of Alzheimer’s Disease as there are no proper medications that are proven as an effective cure. The caregivers should be instructed in the mechanism of action of the disease, safety, and overall treatment goals [3].

Cholinesterase inhibitors

Medications including rivastigmine, galantamine and donepezil could be used to improve cholinergic transmission to delay the degradation process of acetylcholine, which is responsible for producing cognitive and non-cognitive symptoms caused by Alzheimer's disease. Another class of drugs used for controlling the manifested symptoms include N-methyl-D-aspartate (NMDA) antagonist having medium affinity [1].

Antidepressants

Antidepressants such as citalopram and sertraline could be used to manage correlated mental health issues, such as anxiety or depression. Antipsychotic medication such as olanzapine and quetiapine could be used to control agitation [3].

Research is being established to attempt and modify the nature of Alzheimer’s disease. Certain compounds could be used in order to prevent the aggregation of plaques. Anti-aggregation agents includes glycosaminoglycan 3-amino-1-propaneosulfonic acid and colostrinin. Drugs interfering with tau deposition could also be used for that purpose. Vaccination that targets tau protein could be developed and used as a preventive measure [1].

In the future, techniques of therapeutic cloning may be used to treat Alzheimer's disease. The neurons derived from ntESC (nuclear transfer Embryonic Stem Cells) could come to be effective in the treatment of AD, since it is a neurodegenerative disorder.

REFERENCES

The cause of Alzheimer's disease is poorly understood. About 70% of the risk is believed to be inherited from a person's parents with many genes usually involved. Other risk factors include a history of head injuries, depression, and hypertension. The disease process is associated with plaques and neurofibrillary tangles in the brain. A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood tests to rule out other possible causes. Initial symptoms are often mistaken for normal ageing. Examination of brain tissue is needed for a definite diagnosis. Mental and physical exercise, and avoiding obesity may decrease the risk of AD; however, evidence to support these recommendations is weak. There are no medications or supplements that have been shown to decrease risk.

No treatments stop or reverse its progression, though some may temporarily improve symptoms. Affected people increasingly rely on others for assistance, often placing a burden on the caregiver. The pressures can include social, psychological, physical, and economic elements. Exercise programs may be beneficial with respect to activities of daily living and can potentially improve outcomes. Behavioural problems or psychosis due to dementia are often treated with antipsychotics, but this is not usually recommended, as there is little benefit with an increased risk of early death.

In 2015, there were approximately 29.8 million people worldwide with AD. It most often begins in people over 65 years of age, although 4–5% of cases are early-onset Alzheimer's. It affects about 6% of people 65 years and older. In 2015, dementia resulted in about 1.9 million deaths. It was first described by, and later named after, German psychiatrist and pathologist Alois Alzheimer in 1906. In developed countries, AD is one of the most financially costly diseases.

There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.

Current Treatment Options