Tuesday, 28 May 2013

Alzheimer's Disease, what is it, what causes it, how is it treated and how can one prevent oneself from getting it?

Alzheimer's disease (AD), what is it, what causes it, how is it treated and how can we prevent ourselves from getting it? Alzheimer's disease is the most common form of dementia, which are a collection of diseases characterised by an abnormally rapid (beyond what can be explained by the normal process of aging) decline in cognitive functions (memory, learning, problem solving, etc.) particularly memory. While it usually effects the elderly (>65 years of age is usually when the disease begins) it can effect the middle-aged. Risk for AD doubles every five years. In the 60-64 year old cohort around 1% are afflicted by AD whereas in the 85-89 year old cohort around 40% have Alzheimer's disease. (Kumar, 2005)

It is caused by a selective (i.e. other brain regions are largely unaffected) destruction of the cerebral cortex and hippocampus due to, or so we believe, the build up of the proteins amyloid beta (AB) and tau proteins. The hippocampus is a structure of the brain that appears to play a key role in the formation of long-term memories (memories that last years or even indefinitely) from short-term memories and our ability to process the 3D spatial nature of the world we live in. Whereas the cerebral cortex is the grey matter of the brain, the outer layers of the brain where all the information processing occurs. Amyloid beta is a protein that is cleaved by enzymes in the brain from amyloid precursor protein (APP) which is a protein that plays a key role in the formation of synapses and neuronal (electrically signalling brain cells) survival. Tau proteins play key roles in brain development and maintenance. Patients with AD also have evidence of an inflammatory response playing a key role in their conditions. It has also been discovered that those with mutations in the genes that encode apolipoproteins, proteins involved in the breakdown of AB, that end up decreasing their efficiency have an increased risk for AD. Additionally the AB genes are found on chromosome 21, the very chromosome that is repeated in patients with Down's syndrome (DS) and it's been discovered that virtually every patient with DS develops AD before or during their 40s. Most cases of AD cannot be traced to genetics. On average around 5-10% of AD cases can be traced to genetics (Kumar, 2005).

AD is an incurable and relentlessly progressive disease. The usual life expectancy for AD patients is 5-15 years. The usual cause of death in AD patients is pneumonia or dehydration due to the fact that, given sufficient time, patients with AD become immobile, mute and basically empty shells waiting to die leaving pneumonia and dehydration to finish them off.

AD is usually treated by means of drugs and psychotherapy. Psychotherapy usually attempts to help patients and their families cope with the condition better and perhaps attempt to help them deal with some problems that AD can cause such as psychoses (hallucinations, delusions and thought disorders) and depression. Drugs on the other hand tend to include the following:

  • Acetylcholinesterase inhibitors
  • NMDA antagonists 

Acetylcholinesterase (AChE) inhibitors work by inhibiting the enzyme acetylcholinesterase that catalyses the breakdown of the neurotransmitter acetylcholine (ACh). Acetylcholine is a neurotransmitter that plays a wide range of roles in the body. In the brain it is involved in memory and learning, problem-solving, mood, nausea and vomiting regulation, wakefulness and a few other functions whereas in the rest of the body it is involved in our voluntary movements. Nicotine works by activating one set of receptors that respond to acetylcholine whereas the atypical hallucinogen, muscarine, that's found in the mushroom, amanita muscaria (fly amanita) activates the other set of acetylcholine receptors (NOTE: MOST PSYCHEDELIC MUSHROOMS CONTAIN PSILOCYBIN, NOT MUSCARINE, AS THEIR ACTIVE INGREDIENTS. ONLY THIS MUSHROOM CONTAINS SIGNIFICANT QUANTITIES OF MUSCARINE). These sets of acetylcholine receptors are the nicotinic and muscarinic acetylcholine receptors respectively. AChE inhibition in turns leads to an increase in nicotinic and muscarinic acetylcholine receptor activity. Many of the brain cells damaged by AD used acetylcholine for much of their signalling and hence it was theorised that drugs that elevate ACh would reduce the symptoms of AD and while this is true there is a limit as to how much symptomatic relief can be achieved before the inherit toxicity of AChE inhibitors enters the picture. See nerve gases also work via AChE inhibition and hence it should be clear to us that AChE inhibitors are certainly not without their dangers. Examples of AChE inhibitors in clinical practice include:

  • Donepezil (Aricept)
  • Galantamine (Razadyne; derived from a wide range of plants)
  • Physostigmine (antilirium; derived from the calabar bean of tropical Africa)
  • Rivastigmine (Exelon)

NMDA antagonists, unlike AChE inhibitors, are designed to be disease-modifying treatments, that is treatments designed to modify (and in this case slow) the clinical course of AD instead of just improving the symptoms temporarily. We have reason to believe that excitotoxicity, that is neuronal injury due to excess activity of said neuron, plays a key role in the damaging effects of AD on neurons. Since NMDA receptors play a key role in excitotoxicity it was proposed that a NMDA antagonist, such as say, memantine, may act to minimise this damage. It is normally prescribed in moderate-severe AD cases. (Memantine Hydrochloride, n.d.)

Epidemiological (spread/distribution of disease) studies have demonstrated that those that consume coffee and wine regularly, but in moderation, regularly undertake physical and mental exercise, take low doses of non-steroidal anti-inflammatory drugs like ibuprofen and aspirin regularly and have a higher degree of education are less likely to develop AD. High blood pressure, high blood cholesterol, diabetes mellitus and smoking are all risk factors for AD (Lindsay, 2002). There is some evidence to suggest that the regular consumption of antioxidants (e.g. vitamin C, E, green & black teas) (Frank, 2005) and vitamin D can prevent AD. (Lu'o'ng, 2013)

Reference List:

  1. Frank, B., Gupta, S. (2005). A review of antioxidants and Alzheimer's disease. Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 17(4), 269-286. doi: 10.1080/10401230500296428.
  2. Kumar, V., Abbas, A. K., Fausto, N. (2005). Robbins and Cotran Pathologic Basis of Disease 7th Edition. Philadelphia, Pennsylvania: Elsevier.
  3. Lindsay J, Laurin D, Verreault R, H├ębert R, Helliwell B, Hill GB, McDowell I. (2002). Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. The American Journal of Epidemiology. 156(5), 445-453. doi: 10.1093/aje/kwf074.
  4. Lu'o'ng KV, Nguyen LT. (2013). The role of vitamin D in Alzheimer's disease: possible genetic and cell signaling mechanisms. The American Journal of Alzheimer's disease and other Dementias. 28(2), 126-136. doi: 10.1177/1533317512473196.
  5. Memantine Hydrochloride (n.d.). Retrieved May 28 2013 from DrugPoint Summary (Micromedex) for Memantine Hydrochloride.*
*I know I should put the website down but it's utterly useless for my purposes since it requires you to have access to JCU's databases. 

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