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The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN

The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN

The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN