Mild Cognitive Impairment

Because the onset of AD is so slow and symptoms develop gradually over many years, there is a period during which people are slightly more forgetful than they used to be, and perhaps more forgetful than they ought to be. They don't yet have other cognitive or behavioral problems that would classify them as having AD, however. This is the condition that Dr. Petersen named mild cognitive impairment, or MCI. Classifying this condition has been a major boon to researchers because it has provided the parameters within which to study subtle changes in memory and other cognitive skills that may predict the development of AD.

Long-term studies at the Mayo Clinic's Alzheimer's Disease Research Center and with thousands of other research volunteers around the world suggest that people diagnosed with MCI will go on to develop dementia (usually Alzheimer's disease) at a rate of 10-15 percent a year. "We need to identify these people at this earlier stage so that therapies and interventions can be designed to prevent that progression," Dr. Petersen told us. "Ultimately we'd like to identify people who are at risk of developing Alzheimer's disease and other diseases when they still have no symptoms."

Since first describing the condition, Dr. Petersen and other researchers have developed a framework for understanding the causes and consequences of MCI by identifying subtypes. These subtypes are based on the most affected cognitive skills, which may reveal the areas of the brain that are affected as well. Amnestic MCI, the subtype in which memory problems are the most important feature, indicates possible involvement of the hippocampal formation, the memory center of the brain. Other types of MCI, called nonamnestic MCI, are characterized by declines in other cognitive skills, suggesting damage to other brain regions. For example, some people may have visual difficulties or trouble orienting themselves in space. They may be unable to reproduce a drawing or an arrangement of colored blocks. Such deficiencies suggest that other neurodegenerative diseases, such as frontotemporal dementia, as well as vascular or psychiatric conditions, might be causing this nonamnestic MCI.

The classification of two types of MCI—amnestic and nonamnestic—has been widely adopted by AD researchers and investigators conducting AD clinical trials. This framework may have a wider application as well. An understanding of amnestic MCI, combined with other diagnostic tools currently in development and drugs now undergoing clinical trial, may eventually help physicians diagnose and treat people before full-blown Alzheimer's disease has developed.

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Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging