NERVE DEGENERATIVE DISORDERS-PART-III

ALZHEIMER'S DISEASE

Alzheimer's Disease is a cognitive and memory disorder that usually occurs at the age of 60 and above. The onset of the disease is slow but with a definite progression. It may take 10 to 15 years to attain the fully developed stage at which the patient lost short and distant memories, inability to recognize anything, and become immobile with physical sufferings by infections. Death usually resulted in the cause of pneumonia or pulmonary embolism.

Pathophysiology 

The major pathophysiology is the atrophy and damages of the cerebral cortex and subcortical neurons. Unlike PD, in AD, there are no much damages at the midbrain and hence there are no postural and extrapyramidal irregularities.

In the process of aging, there is a synthesis of neurons are progressed at the cerebral cortex usually in the grey matter. During the process, by-products are formed as plaques and deposited at the grey matter.

These deposits are larger in number and are mainly made of beta-amyloid. These plaques are neurotoxic and cause further degenerations of neurons in the cortex results in Alzheimer's Disease(AD). 

Although small numbers of senile plaques and neurofibrillary tangles are common in normal individuals they are far more abundant in AD and the abundance is directly proportional to the cognitive impairment.

Unlike Parkinson's Disease in which the main pathophysiology is the loss of dopaminergic neurons in the midbrain but in Alzheimer's Disease, there is a major loss of cholinergic neurons with a hefty insufficiency of acetylcholine input at the cerebral cortex particularly at the basal forebrain that provide cholinergic innervation to the whole cerebral cortex. Also unlike in PD in AD, there is far more loss of neurotransmitter networks such as serotonin, glutamate, and neuropeptides to make it more complicated.

Treatments

One of the major basics of the treatment of the AD is to restore or normalize the acetylcholine input and to normalize the cholinergic innervation of the cortex. The approach with acetylcholine precursors such as choline chloride and lecithin was found with no expected benefits.

Direct injection of cholinergic agonists such as bethanechol into the intracerebroventricular region yield some benefits. But this is complicated with the need for surgical implantation of a reservoir connecting to the subarachnoid space(the space between the arachnoid mater and the pia mater ).

Later on, there are some more easy and improved methods such as the use of acetylcholinesterase inhibitors such as physostigmine a reversible inhibitor are developed. The use of physostigmine is limited because of its short half-life and side effects like a cholinergic crisis in therapeutic doses.

Recently the American FDA has approved a drug known as tacrine an acridine derivative for the treatment of AD. It is a potent centrally acting inhibitor of the enzyme AchEsterase.An I.V.injection of tacrine is tried with major flaws

Laer on oral tacrine combined with lecithin is tried successfully.

Side effects of oral tacrine

1.Abdominal cramp

2.Nausea and vomiting

3.Diarrhea

4.Liver toxicity(elevation of serum transaminases)

but liver enzymes rapidly subsided by withdrawing the medicine.