Truth About Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia in western countries. AD is caused to lack of acetylecholine in brain. Approximately 10% above 70 years have significant memory loss and at least more than half of this is due to Alzheimer’s disease. AD most commonly presents as subtle loss of memory and it is followed by slowly progressive memory loss, and that has a course of several years (8-10 years). AD can occur at any time during adult life. Cost of treatment in USA is nearly $ 75,000 per year, which is a staggering sum of money, which also extracts a heavy emotional toll on family and friends and caregivers. Patho physiology of AD is diffuse atrophy of cerebral cortex and secondary enlargement of ventricular system. Neuritic plaques containing amyloids are seen in microscopy, and also accumulation of amyloids in the arterial walls of cerebral blood vessels. Four susceptible genes have been identified to cause AD.ID-10094878

Clinical symptoms of AD follow a characteristic pattern, which starts with simple memory loss, impairment of language comprehension and visual deficit. Around 20% of AD patients presents with problem of word comprehension, organizational problems and difficulty in finding places. In early stage of AD memory loss may go unrecognized or may present as simple forgetfulness. Mild Cognitive Impairment (MCI) is the term used when memory loss causes day to day activity disturbance. Slowly MCI starts to disturb daily activities like keeping tracks of finances, daily activities in job, driving automobile, shopping and housekeeping. Some of the patients are not aware of their difficulty which is called anosognosia. Change in environment may be puzzling. Patient may get lost during routine walk, or while driving automobile patient may loose direction. In the middle stage of AD patient is unable to work at his job, he is confused, easily lost and need supervision. Sometimes patient may surprisingly retain superficial conversation, social grace, and routine behaviors. Language is impaired, at first naming then comprehension, and then fluency is lost. Apraxia (inability to use objects correctly) develops, aphasia (loss of power of expression by speech, writing, or sign, or comprehending spoken or written language), visual deficit, interfere with dressing, eating, solving simple puzzles develops. Patient may be unable to do simple calculations and tell time. In late stage some patients remain ambulatory but may wander aimlessly. There is loss of judgment and reasoning. Delusion which may include theft, infidelity, and difficulty in identification is seen. 10% develop Capgras syndrome (believing that the caregiver is an imposter). Sleep pattern is lost; somnambulism (walking during sleep) is a big problem for the patient and family members. Patients become mute, bedridden and incontinence of urine develops. Help is required for simple tasks like, dressing, eating, and toilet function. Sudden brief contraction of some muscles or whole body may occur spontaneously, in response to physical or auditory stimulus. Generalized seizure may develop and cause sudden death. Duration of disease is usually 8-10 years but may range from 1-25 years.

Diagnosis of Alzheimer’s disease is mainly based on clinical symptoms. In early stages of AD other causes of dementia should be excluded. EEG shows non specific changes. Genotyping of blood is done to find out susceptible genes. CT or MRI is not specific. As AD progresses diffuse atrophy of cortex is seen in MRI. Several genes have been identified which play important role in pathophysiology of AD. The first to be identified was APP gene on chromosome 21. Point mutation of APP gene produces autosomal dominant AD. Adults with trisomy 21 (Down’s syndrome) who survive beyond 40 years of age develop progressive dementia which is accompanied by typical symptoms of AD, which proves its relationship with APP gene. Investigation of large number of families with AD for many generation found that two other genes other than APP gene are responsible. They are Presenilin-1 (PS-2) and Presenilin-2 (PS-1). PS-1 is on chromosome 14 and PS-2 is on chromosome 1. PS-1 encodes a protein called S182, mutation of which can cause early onset of AD, onset much before age 60. PS-2 gene encodes a protein called STM2. PS-1 and PS-2 are homologous. Mutation with PS-1 causes early onset AD with mean age of development at 45 years. This type of AD is rapidly progressive with mean duration of 6-7 years.

Most important risk factor is old age, and positive family history. Frequency of AD increases every decade. In western countries AD is about 30% in people above 80 years of age. Due to longer lifespan females are more prone to develop AD. In one study it was found that the capacity to express complex written language and understand in adulthood correlates with a decrease in the risk of developing AD in later years. Pathology is found in temporal cortex and hippocampus. Most important microscopic finding is neuritic plaques. These plaques accumulate during normal aging but in AD they are present in excess. These plaques contain A? amyloids , proteoglycon ? , antitrypsin and other proteins. A? amyloid is a protein of 39 to 42 amino acids. Accumulation of A? amyloid in cerebral cortex is called amyloid angiopathy, which lead to cerebral hemorrhage and reduction of acetyl choline results from degeneration of cholinergic neurons. There is also reduction of norepinephrine in brain stem.

Alzheimer’s disease can not be cured. Drugs are not effective. Focus should be on symptomatic treatment of patient and building a rapport with family members and caretakers. Cholinesterase inhibitor drugs should be used judiciously. Donepezil, rivastigmine, and galantamine are approved by US FDA (food & drug administration) for use in AD. They inhibit cholinesterase thereby increasing levels of acetylecholine in brain. They improve functioning of patients. Donepezil has less liver toxicity than other drugs and also it is cheap, so it is more commonly used than other drugs. It is given at the dose of 5-10 mgs once daily. In patients, with mild AD, antioxidants selegeline, and vitamin E also helpful. The dose of vitamin E 1000 IU twice daily. A control trial study with Ginkgo biloba found to improve symptoms of AD. The latest strategy of treatment of AD is to develop a vaccine against A? amyloid, which has shown excellent results in mouse models but gave rise to life threatening meningoencephalitis in human volunteers. In mouse models this vaccine could clear amyloid deposits and improve cognitive function. This vaccine develop antibody against A? amyloid, which cross Blood Brain Barrier (BBB). Scientists are trying to find out a solution to this problem with the vaccine. Several retrospective studies have found that statins (HmgCOA reductase inhibitors) and NSAIDs (non steroidal anti-inflammatory drugs) may protect against dementia. Mild to moderate depression common in early stage of AD responds to routine antidepressants. Selective serotonin reuptake inhibitors (SSRI) are also used. Finally it is the sympathetic approach to the patient and his family and friends which goes a long way in the management of Alzheimer’s disease.


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