Alzheimer’s disease

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Alzheimer's Disease

Alzheimer’s disease is a progressive form of dementia. Dementia is a broader term for conditions caused by brain injuries or diseases that negatively affect memory, thinking, and behavior. These changes interfere with daily living.
According to the Alzheimer’s Association, Alzheimer’s disease accounts for 60 to 80 percent of dementia cases. Most people with the disease get a diagnosis after age 65. If it’s diagnosed before then, it’s generally referred to as early onset Alzheimer’s disease.

Alzheimer's Disease Causes

The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is the most widely discussed and researched hypothesis about the cause of Alzheimer's disease. The strongest data supporting the amyloid cascade hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease. Mutations associated with Alzheimer's disease have been found in about half of the patients with early-onset disease. In all of these patients, the mutation leads to excess production in the brain of a specific form of a small protein fragment called ABeta (Aβ). Many scientists believe that in the majority of sporadic (for example, non-inherited) cases of Alzheimer's disease (these make up the vast majority of all cases of Alzheimer's disease) there is too little removal of this Aβ protein rather than too much production. In any case, much of the research in finding ways to prevent or slow down Alzheimer's disease has focused on ways to decrease the amount of Aβ in the brain.

Symptoms of Alzheimer's

Everyone has episodes of forgetfulness from time to time. But people with Alzheimer’s disease display certain ongoing behaviors and symptoms that worsen over time. These can include:
  • memory loss affecting daily activities, such as an ability to keep appointments
  • trouble with familiar tasks, such as using a microwave
  • difficulties with problem-solving
  • trouble with speech or writing
  • becoming disoriented about times or places
  • decreased judgment
  • decreased personal hygiene
  • mood and personality changes
  • withdrawal from friends, family, and community
The symptoms of Alzheimer’s disease will change according to the stage of the disease.

Alzheimer’s Treatment

There’s no known cure for Alzheimer’s disease, available treatments offer relatively small symptomatic benefit but remain palliative in nature.
The treatment of Alzheimer's disease consists of medication based and non-medication based. Two different classes of pharmaceuticals are approved by the FDA for treating Alzheimer's disease: cholinesterase inhibitors and partial glutamate antagonists. Neither class of drugs has been proven to slow the rate of progression of Alzheimer's disease. Nonetheless, many clinical trials suggest that these medications are superior to placebos (sugar pills) in relieving some symptoms.
Medication Based Treatment
▪ Cholinesterase inhibitors (ChEIs)
In patients with Alzheimer's disease there is a relative lack of a brain chemical neurotransmitter called acetylcholine. Substantial research has demonstrated that acetylcholine is important in the ability to form new memories. The cholinesterase inhibitors (ChEIs) block the breakdown of acetylcholine. As a result, more acetylcholine is available in the brain, and it may become easier to form new memories.
Four ChEIs have been approved by the FDA, but only donepezil hydrochloride (Aricept), rivastigmine (Exelon), and galantamine (Razadyne - previously called Reminyl) are used by most physicians because the fourth drug, tacrine (Cognex) has more undesirable side effects than the other three. Most experts in Alzheimer's disease do not believe there is an important difference in the effectiveness of these three drugs. Several studies suggest that the progression of symptoms of patients on these drugs seems to plateau for six to 12 months, but inevitably progression then begins again.
Of the three widely used ChEIs, rivastigmine and galantamine are only approved by the FDA for mild to moderate Alzheimer's disease, whereas donepezil is approved for mild, moderate, and severe Alzheimer's disease. It is not known whether rivastigmine and galantamine are also effective in severe Alzheimer's disease, although there does not appear to be any good reason why they shouldn't.
The principal side effects of ChEIs involve the gastrointestinal system and include nausea, vomiting, cramping, and diarrhea. Usually these side effects can be controlled with change in size or timing of the dose or administering the medications with a small amount of food. A majority of patients will tolerate therapeutic doses of ChEIs.
▪ Partial glutamate antagonists
Glutamate is the major excitatory neurotransmitter in the brain. One theory suggests that too much glutamate may be bad for the brain and cause deterioration of nerve cells. Memantine (Namenda) works by partially decreasing the effect of glutamate to activate nerve cells. Studies have demonstrated that some patients on memantine can care for themselves better than patients on sugar pills (placebos). Memantine is approved for treatment of moderate and severe dementia, and studies did not show it was helpful in mild dementia. It is also possible to treat patients with both AchEs and memantine without loss of effectiveness of either medication or an increase in side effects.
Besides, many studies shows that J147, CAD-31, CMS 121, etc drugs would be effective for Alzheimer's disease in the mouse models of accelerated aging. J147 is an experimental drug with reported effects against both Alzheimer's disease and ageing in mouse models of accelerated aging. And enhanced neurogenic activity over J147 in human neural precursor cells has its derivative called CAD-31.
Non-medication based treatment
In addition to medication, lifestyle changes may help alzheimer's disease patient
manage their condition, such as reading books (but not newspapers), playing board games, completing crossword puzzles, playing musical instruments, or regular social interaction show a reduced risk for Alzheimer's disease.

Reference:

  1. Matthews, K. A., Xu, W., Gaglioti, A. H., Holt, J. B., Croft, J. B., Mack, D., & McGuire, L. C. (2018). Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged≥ 65 years. Alzheimer’s & Dementia. https://doi.org/10.1016/j.jalz.2018.06.3063external icon
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  3. Alzheimer's disease - Causes (NHS)
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  7. "Experimental drug targeting Alzheimer's disease shows anti-aging effects" (Press release). Salk Institute. 12 November 2015. Retrieved November 13, 2015