Brain Building

Education is the factor that has received by far the most attention among Alzheimer's disease researchers interested in cognitive reserve, because of its strong correlation with cognitive performance noted in the studies described above. However, Dr. Bennett brings a unique perspective to this field of study, and an expansive way of thinking about all the factors that might contribute to the creation of an efficient brain.

One of the out-of-the-box ways that Dr. Bennett has approached thinking about brain activity is to consider how people must develop semantic memory—generalized knowledge that does not involve memory of a specific event—each time they interact with someone they know. Consider that the brain has to work hard to help a person maintain a social network. If a man bumps into an old friend, somebody he hasn't seen in twenty years, he recalls in an instant how he knows her, whether she's married, has children, and so on. This task alone stimulates the brain. Then the old information is integrated with the new information from the current encounter, which is stored in his memory bank so he is able to call it all up again the next time he meets her. People with complex social networks are constantly engaging with others in this way, updating their brain files. Perhaps, like formal education, this stimulates the brain and creates more cognitive reserve.

It turns out that having many friends and participating in social activities have been associated with reduced cognitive decline and decreased risk of dementia in older adults. For example, the National Institute on Aging-funded Memory and Aging Project, which Dr. Bennett directs, found an association between higher levels of social engagement and better cognitive function over time.

Dr. Bennett's other major study, the Religious Orders Study, also has associated a high level of cognitive activity with reduced Alzheimer's disease risk. Investigators on that project periodically asked study participants —older nuns, priests, and religious brothers—to describe how much time they spent in seven information-processing activities: having a conversation, reading a book, listening to the radio, watching television, reading newspapers, playing puzzle games, and going to museums. After following the volunteers for four years, investigators found that the risk of developing AD was, on average, 47 percent lower for participants who did the activities most frequently than for those who did them least frequently. Other studies have shown similar results. In addition, a growing body of research, including other findings from the Religious Orders Study, has associated a higher level of education with increased memory and learning abilities, even when a person has sufficient deposition of beta-amyloid plaques to qualify for a diagnosis of AD.

Because late-life cognitive activity is likely related to lifelong engagement in cognitively stimulating activities, Dr. Bennett and colleagues examined lifelong learning and mentally stimulating activity among participants in the Rush Memory and Aging Project. After following the research volunteers for up to five years, investigators found that both current and past activities were related to risk of AD. Importantly, even after accounting for the effects of past activity, people in the bottom 10% for current activity level were nearly three times as likely to develop AD as those in the top 10% of activity. Other studies have shown that people who are bilingual or multilingual seem to develop AD at a later age than do people who speak only one language.

Although these findings are provocative, they still need to be interpreted with caution. It's not always possible to tell whether Alzheimer's disease is the cause or the consequence of limited participation in social activities. The disease develops over the course of decades before symptoms appear, and it is possible that early AD could cause a person to limit social or intellectual activities. However, Dr. Bennett did not find a relationship between participation in cognitive activity and AD pathology in the brain. This suggests that level of cognitive activity was unlikely to be a result of AD and that whatever benefit is derived from cognitive activity is likely the result of its effect on brain reserve.

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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