Treatment guidelines for Alzheimer-type dementia: the most common dementia in the elderly, Alzheimer disease places tremendous physical and emotional strain on patient and caregiver alike

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Date: June 2011
From: Clinical Advisor(Vol. 14, Issue 6)
Publisher: Haymarket Media, Inc.
Document Type: Article
Length: 5,670 words
Lexile Measure: 1680L

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The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSMIV-TR) defines dementia of the Alzheimer type as the development of multiple cognitive deficits manifested by both memory impairment and one or more cognitive disturbances. (1) The deterioration of intellectual function and other cognitive skills leads to a decline in the ability to perform activities of daily living (ADLs). (2) This decline occurs with a normal state of consciousness and in the absence of other acute or subacute disorders that may cause reversible cognitive deterioration, such as those seen in delirium or depression. (3)

Prevalence

Alzheimer disease (AD) is estimated to affect 6% to 10% of the U.S. population older than age 65 years. (4) It has been estimated that the number of AD patients will reach 13.2 million by 2050, with a per-patient cost of approximately $91,000 over the course of the illness. (5)

Causes

AD is a primary neurodegenerative disorder. There are several competing theories that attempt to explain a singular cause of AD. The oldest of these is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. (6) The cholinergic hypothesis has been criticized, largely because medications intended to treat acetylcholine deficiency have not yielded dramatic results.

In 1991, the amyloid hypothesis proposed that amyloid-beta deposits are the primary cause of AD. (7) This theory was supported by research that revealed the location of the gene for the amyloid-beta precursor protein (APP) on chromosome 21. The hypothesis is made much more credible by the fact that people with trisomy 21, who thus have an extra gene copy, ubiquitously exhibit AD by aged 40 years. (8)

Apolipoprotein E (APOE3), a major genetic risk factor for AD, leads to excess amyloid buildup in the brain before symptomatology arises. Thus, amyloid-beta deposition precedes clinical AD. (9) More evidence comes from the study of transgenic mice that express a mutant form of the human APP gene and develop fibrillar amyloid plaques and Alzheimerlike brain pathology with spatial learning deficits. (10)

In 2009, this theory was revamped, suggesting that a close relative of the beta-amyloid protein and not the beta amyloid specifically may be a major causative factor of the disease. The theory maintains that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by aging-related processes in later life to cause the neuronal withering of AD. (11)

A 2004 study found no correlation between the deposition of amyloid plaques and neuron loss. (11) This observation brought about more support for the tau hypothesis, which contends that tau protein abnormalities initiate the disease cascade. (12) In this model, hyperphosphorylated tau begins to pair with other threads of tau. Ultimately, they form neurofibrillary tangles inside nerve-cell bodies. (13) When this occurs, the microtubules disintegrate, causing the collapse of the neuron's transport system. (14)

The most recent literature posits a constellation of the aforementioned occurrences--including amyloid deposition, neurofibrillary tangles, synaptic losses, cholinergic dysfunction, selective...

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Gale Document Number: GALE|A263519856