Building Cognitive Reserve

Now that PET scans with PiB can measure beta-amyloid levels in a living brain, studies have found that about 25 percent of seventy-year-olds have evidence of one pathology of Alzheimer's disease—beta-amyloid plaques—even without showing clinical symptoms of memory loss or cognitive decline. Although these people are cognitively normal, they have a substantial plaque load.

Dr. David Bennett, the director of the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago, has been researching this phenomenon. He is intrigued by cases like a ninety-year-old nun who had shown no decline in cognition, but was found to have a substantial amount of beta-amyloid plaques upon autopsy. He wondered how she could have so much beta-amyloid in her brain, but experience no evident memory loss.

Scientists do not doubt that beta-amyloid changes the brain, but researchers like Dr. Bennett are focusing on what enables some people's brains to withstand what could be damaging effects. Do they have a bigger brain, a better brain, a more efficient brain, or something else? In some cases, the brain may have some sort of "cognitive reserve," the ability to operate effectively even while damage is occurring.

Alzheimer's disease researchers, such as Dr. Bennett, are working to understand why some people have these brain reserves, which seem to protect them from the presumed damage by beta-amyloid. What protective role might brain efficiency play? Could different personality traits make someone more or less susceptible to AD? How might early life experiences and lifelong behaviors affect the disease?

In particular, Dr. Bennett is studying the possible impact on the aging brain of behavior, lifestyle, and education. As the lead researcher on two major observational studies—the Rush Memory and Aging Project and the Religious Orders Study—he heads a team that is collecting detailed family histories, socioeconomic data, and records of performance on cognitive exams over time from more than twenty-three hundred individuals and retirement home residents, including older Catholic nuns, priests, and brothers living in forty communities across the United States. All participants agree to donate their brains to science upon their death and, to date, Dr. Bennett has collected more than seven hundred brains to study. A third of the people enrolled in the study, including the nun described above, are found upon autopsy to have fully developed Alzheimer's disease plaque pathology without any obvious cognitive problems. He hypothesizes that cognitive reserve may be preventing these brains from expressing clinical signs of Alzheimer's disease.

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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