Alzheimer's is a progressive neurodegenerative condition, chiefly defined by the steady accumulation of toxic protein masses called amyloid plaques and neurofibrillary tangles in areas of the brain necessary for processing factual information. Due to these masses, the cells that are the building blocks for these areas--neurons--eventually lose the physical contacts or "synapses" that link them to one another and provide the ability to communicate. Failures to reestablish the connections result in the behavioral symptoms that are commonly observed in people with Alzheimer's, such as cognitive impairment and depression. According to the Alzheimer's Association, as many as 16 million Americans will be diagnosed with Alzheimer's-related dementias by 2050. Treatments for brain damage in the basal forebrain, medial temporal lobe and neocortex are urgently needed to stem this growing tide.
Basal Forebrain
The basal forebrain is formed from a small collection of cell groups at the very bottom of the frontal lobe. The cells produce the chemical messenger acetylcholine; they widely extend connections to various regions of the brain that specialize in learning and memory or in storing long-term knowledge, including the hippocampus and neocortex. Acetylcholine function is critical for maintaining wakefulness and attention. Not surprisingly, the loss of acetylcholine that occurs as a consequence of basal forebrain degeneration leads to concentration lapses (e.g., sudden forgetfulness, trouble following conversation) in people suffering through the early and mid-stages of Alzheimer's. Most drugs approved by the U.S. Food and Drug Administration (FDA) for Alzheimer's treatment are designed to increase the levels of this chemical.
Medial Temporal Lobe
The medial temporal lobe comprises a network of interwoven brain structures that jointly encode and retrieve the details surrounding personal events. One of these structures, a seahorse-shaped region called the hippocampus, is specifically responsible for consolidating short-term memories into longer term ones. In work spanning three decades, Dr. Robert Sapolsky, a MacArthur Fellow and Professor of Neurology at Stanford University, has demonstrated that damage to the hippocampus not only interferes with cognition but can also have ramifications for how people deal with stress. As such, hippocampal atrophy (tissue shrinkage) might contribute to both the intellectual and emotional problems commonly experienced by Alzheimer's patients.
Neocortex
The progression of Alzheimer's is different from one person to the next. However, the National Institute on Aging indicates that one of the last parts of the brain to show degeneration in response to the disease process is the neocortex, a region that covers the brain's outer contour or surface. Subdivisions of the neocortex--such as the frontal, motor and parietal cortices--are responsible for maintaining higher-order thought: semantic knowledge (e.g., knowing the sky is blue), decision making, moral and value judgments, motor planning, defining personal from extra-personal, three-dimensional space. The extent of damage seen in these areas during severe-stage Alzheimer's correlates with the degree of personhood maintained by Alzheimer's-affected individuals.
References
- Alzheimer's Association, Disease Facts and Figures
- U.S. National Library of Medicine, R. Schliebs and T. Arendt, "The Significance of the Cholinergic System in the Brain during Aging and in Alzheimer's Disease"
- U.S. National Library of Medicine, B.C. Dickerson and R.A. Sperling, "Functional Abnormalities of the Medial Temporal Lobe Memory System in Mild Cognitive Impairment and Alzheimer's Disease: Insights from Functional MRI Studies"
- Proceedings of the National Academy of Science, R. Sapolsky, "Depression, Antidepressants, and the Shrinking Hippocampus"
- National Institute on Aging, Alzheimer's Disease Fact Sheet
