Introduction

Alzheimer’s disease is a progressive, ultimately fatal, disorder in which certain types of nerve cells in particular areas of the brain degenerate and die for unknown reasons.

Vulnerable brain regions include the amygdala as well as the hippocampus and areas around the hippocampus, and affected cell populations include cortical pathways involved in catecholaminergic, seritonergic and cholinergic transmission. Advancing pathology is believed to underlie the classic clinical presentation of memory deficits followed by gradual erosion of judgment, reasoning ability, verbal fluency and other cognitive skills.

Pathology

The two "hallmark" Alzheimer lesions observable at autopsy – first described by German neuropsychiatrist Alois Alzheimer in 1906 – are amyloid plaques and neurofibrillary tangles. Plaques are extracellular deposits of abnormally processed amyloid precursor protein, and tangles are intracellular accumulations of the cytoskeletal protein tau.

Researchers now recognize that development of plaques and tangles may represent a fairly late-stage in the disease process that may or may not reflect the fundamental biochemical disruptions at work in Alzheimer’s. Although the "amyloid hypothesis," which assigns a central causative role to abnormal amyloid processing, remains the most widely embraced theory, other active areas of research include tau, inflammation, disruptions of cell signaling pathways and cardiovascular risk factors.

Management

Key elements of disease management include timely diagnosis and effective use of available therapies to manage cognitive and behavioral symptoms. Other important considerations include identifying comorbid conditions and monitoring individuals for adequate nutrition, hydration and pain management as well as signs of abuse.

Drugs currently approved specifically to treat Alzheimer symptoms all act chiefly by inhibiting acetylcholinesterase, the main enzyme that breaks down acetylcholine. For about 50 percent of the individuals who take them, these drugs offer a modest, temporary delay in worsening of cognitive symptoms. But cholinesterase inhibitors do not stop underlying neurodegeneration, and the disease inevitably progresses.