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Tuesday, 29 October 2013

Dementia Treatments of Alzheimer's disease and Diminished quality of acetylcholine In conventional Medicine Perspective

Dementia
About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability that is severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people. American typical diet contains high amount of saturated and trans fat, artificial ingredients with less fruits and vegetable which can lead to dementia and other kind of diseases.

Treatments
Depending to the causes of disease, most medication are to control the symptoms 
A. Alzheimer's disease and Diminished quality of acetylcholine
A.1. Treatments of mild and moderate Alzheimer's disease and Diminished quality of acetylcholine
1. Cholinesterase inhibitors 
a. Cholinesterase inhibitors are the primary treatment, including tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) for the cognitive symptoms of Alzheimer disease (AD). Dr. Trinh NH and the research team at the Massachusetts General Hospital, showed that for neuropsychiatric outcomes, 10 trials included the ADAS-noncog and 6 included the NPI. Compared with placebo, patients randomized to cholinesterase inhibitors improved 1.72 points on the NPI (95% confidence interval [CI], 0.87-2.57 points), and 0.03 points on the ADAS-noncog (95% CI, 0.00-0.05 points). For functional outcomes, 14 trials used ADL and 13 trials used IADL scales. Compared with placebo, patients randomized to cholinesterase inhibitors improved 0.1 SDs on ADL scales (95% CI, 0.00-0.19 SDs), and 0.09 SDs on IADL scales (95% CI, 0.01 to 0.17 SDs). There was no difference in efficacy among various cholinesterase inhibitors(1). Some researchers suggested that Persistent drug treatment had a positive impact on AD progression assessed by multiple cognitive, functional, and global outcome measures. The magnitude of the treatment effect was clinically significant. Positive treatment effects were even found in those with advanced disease(2). Some researchers suggested that if there is a decrease in the level of acetylcholine, a chemical messenger that assists memory, thought and judgment, then cholinesterase inhibitors may eventually lose their effect. In the article, Cholinesterase Inhibitors, posted in the Minister of health, the author(s) wrote that Cholinesterase inhibitors were developed to improve the effectiveness of acetylcholine either by increasing the levels in the brain or by strengthening the way nerve cells respond to it. Increased concentrations of acetylcholine in the brain lead to increase communication between nerve cells and may temporarily improve or stabilize the symptoms of Alzheimer's disease. These drugs appear to work best in the early and moderate stages of Alzheimer's Disease(3).

b. Side effects are not limit to
b.1. Nausea    
b.2. Diarrhea    
b.3. Vomiting    
b.4. Indigestion.     
b.5. Abdominal pain    
b.6. Loss of appetite
b.7. Fatigue
b.8. Weight loss
b.9. Etc.

A.2. Treatment of moderate and Severe Alzheimer's disease and Diminished quality of acetylcholine
a. Namenda® (memantine), an N-methyl D-aspartate (NMDA) antagonist are the most common medication used to moderate and Severe Alzheimer's disease.Scientists at the Brigham and Women's Hospital, Harvard Medical School, indicated that The key to memantine's therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine's tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects(7). Others suggested that Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine but not those in vascular dementia(8).

b. Side effects are not limit to
b.1. Confusion,
b.2. Dizziness
b.3. Drowsiness
b.4. Headache
b.5. Insomnia,
b.6. Agitation
b.7. Vomiting
b.8. Anxiety
b.9. Etc.
  
A.3. Other medication
3.1. Anticonvulsants
a. Anticonvulsants are a diverse group of pharmaceuticals used in the treatment of seizures, the clinical syndrome of Alzheimer's disease by suppressing the rapid and excessive firing of neurons that start a seizure. Some research suggested that Seizure pathophysiology may relate to increased amyloid beta-peptide production, structural alterations in neurones related to cytoskeletal dysfunction, cerebrovascular changes, neurotransmitter dysfunction or combinations thereof. Through modification of these pathophysiological pathways, there may be possible roles for anti-epileptic drugs such as sodium valproate and lacosamide in the treatment of Alzheimer's disease(4)

b. Side effects are not limit to
b.1. Dizziness
b.2. Drowsiness
b.3. Unsteadiness
b.4. Nausea
b.5. Vomiting
b.6. Skin rashes
b.7. Etc.

3.2. Sedatives
a. A sedative or tranquilizer is a drug that calms a patient, reducing irritability and excitement by by modulating signals within the central nervous system.The medication are highly addictive. Researchers at the Weill Cornell Medical College showed that antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time(5).
 
b. Side effects are not limit to
b.1. Stomach upset
b.2. Blurred vision
b.3. Headache
b.4. Impaired coordination
b.5. Depression
b.6. Memory loss
b.7. Drowsiness
b.8. Etc.

3.3. Antidepressants
a. Antidepressant is a type of psychiatric medication used to treat depression, including mood disorder, dysthymia and anxiety disorders.In the study to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription, Dr. Arbus C, and the team at the Purpan-Casselardit Hospital, suggested that Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression(6).

b. Side effects are not limit to
b.1. Dry mouth, 
b.2. Blurred vision
b.5. Drowsiness, 
b.4. Dizziness
b.5. Tremors
b.6. Sexual problems
b.7. Etc. 
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Sources

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/12517232
(2) http://www.ncbi.nlm.nih.gov/pubmed/19845950
(3) http://www.health.gov.bc.ca/pharmacare/adti/clinician/cholinesterase.html

(4) http://www.ncbi.nlm.nih.gov/pubmed/19557550
(5) http://www.ncbi.nlm.nih.gov/pubmed/20980585
(6) http://www.ncbi.nlm.nih.gov/pubmed/19735591
(7) http://www.ncbi.nlm.nih.gov/pubmed/21875407
(8) http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003154.pub4/abstract;jsessionid=81B82BC5B10FAB9959A92CF39D439C21.d02t02