Education may be protective for people with gene for familial early onset Alzheimer's
August 5, 2020
Science Daily/American Academy of Neurology
Even for people who carry the gene for early onset Alzheimer's disease, more years of education may slow the development of beta-amyloid plaques in the brain that are associated with the disease, according to a new study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
About 1-6% of people with Alzheimer's disease have rare genes that cause the disease in everyone who has them. This is called familial Alzheimer's disease. It leads to an early onset of the disease, when people are in their 30s to 50s.
"Because we've assumed that the effects of these genes can't be changed, very little research has been done on whether we can modify the trajectory of the disease," said study author Sylvia Villeneuve, PhD, of the McGill University in Montreal, Canada. "It's exciting to see that education may play a role in delaying the start of this devastating disease, which affects people during the prime of life."
Most people diagnosed with Alzheimer's have the sporadic form of the disease, which is thought to be caused by a combination of both environmental and genetic factors, including a gene variant called APOE ?4, or apolipoprotein E ?4. Having this gene variant is known to increase the development of amyloid plaques in the brain, even though it does not guarantee that the person will develop symptoms of Alzheimer's disease.
The study involved two groups: one group of 106 people with an average age of 67 who had a parent diagnosed with the sporadic form of Alzheimer's disease, of whom 39% had the APOE ?4 gene variant; and another group of 117 people with an average age of 35 who had the gene mutations linked to familial early onset Alzheimer's disease, of whom 31% also had the APOE ?4 gene variant. Each group had an average 15 years of education. None of the participants showed symptoms of the disease at the start of the study.
Participants had brain scans to determine levels of amyloid plaques.
Researchers found that in the people with familial early onset Alzheimer's, increasing levels of education were associated with lower levels of amyloid plaques in the brain. The strength of the association between education and plaque levels was similar to the strength of this same association in people at risk of sporadic Alzheimer's disease.
In both groups, people with less than 10 years of education had about twice the amount of amyloid plaques when compared to people with more than 16 years of education.
"While it has been believed that people with familial Alzheimer's disease, with its strong genetic causes, may have few ways to slow development of the disease, our study shows that education may be somewhat protective, perhaps promoting brain resistance against these plaques, just as it has been shown to be in people with unknown causes of the disease," said Villeneuve.
A limitation of the study was that most participants were white, so results may not be the same for all people. Also, the quality of education may be affected by other factors like socioeconomic status, so future studies should look more closely at other factors in addition to years of education to determine whether other environmental factors may be at play to explain these study results.
https://www.sciencedaily.com/releases/2020/08/200805160829.htm
Subtle decline in cognition predicts progression to Alzheimer's pathology
February 14, 2020
Science Daily/University of California - San Diego
Researchers report that abnormal levels of beta-amyloid plaques in brain predict cognitive decline and higher risk of developing Alzheimer's disease, but also that cognitive performance predicts progression from normal to abnormal levels of beta-amyloid.
Alzheimer's disease (AD) is progressive, but slow to develop -- or at least to reveal itself. In a new study, published online February 14, 2020 in the journal Biological Psychiatry, researchers at University of California San Diego School of Medicine, with colleagues elsewhere, report that early, subtle differences in cognitive performance, such as fewer words recalled on a memory test, are a sign that harmful proteins are accumulating in the brain, even if levels of those proteins do not yet qualify as dangerous.
Pathologically, AD is primarily characterized by the accumulation of protein plaques called β-amyloid (Aβ), which gradually accumulate in the brain, disrupting cell function and eventually killing affected neurons. A second type of protein, called tau, also accumulates abnormally inside neurons, damaging functions.
In the progression of AD, Aβ levels build in the brain, but the process leading to abnormally high levels is typically long. It is often years or decades before consequential symptoms of severe cognitive impairment appear. A new framework from the National Institute on Aging and Alzheimer's Association defines the first stage of AD to be individuals with abnormal levels of Aβ who are still cognitively normal.
"Although AD pathology, and Aβ in particular, appear long before severe cognitive deficits appear," said first author Jeremy A. Elman, PhD, assistant professor in the Department of Psychiatry at UC San Diego School of Medicine, "recent evidence suggests more subtle cognitive changes may appear earlier in the disease than commonly appreciated."
Elman and colleagues, including senior author William S. Kremen, PhD, professor of psychiatry at UC San Diego School of Medicine, sought to determine whether poor cognitive performance, however subtle, might be a predictor that current Aβ-negative levels (accumulations below the threshold for AD diagnosis) were likely to become Aβ-positive.
"Once a person reaches the point of being Aβ-positive, it means that there is already substantial underlying pathology," said Kremen. "It would be advantageous to identify at-risk individuals before they develop substantial amyloid burden to improve treatment efficacy and slow progression to AD dementia."
The researchers conducted a pair of non-invasive cognitive tests on 292 participants in the Alzheimer's Disease Neuroimaging Initiative, an ongoing study to assess whether the use of medical imaging, biological markers and clinical assessments can be combined to measure the progression of cognitive decline and early AD.
All of the participants were Aβ-negative at baseline testing and displayed no dementia; 40 participants would progress to Aβ-positivity during the study and follow-up period.
The scientists found that participants who tested with lower baseline cognition were at significantly higher risk of progressing to Aβ-positivity. That is, low test scores indicating poorer cognitive function suggested amyloid plaque levels that, while not yet considered to be problematic, were likely rising and would ultimately reach the threshold definition of AD.
"We found that subthreshold levels of baseline Aβ were predictive of future accumulation, adding to evidence that even low levels of Aβ are clinically relevant, but that cognitive performance was still significantly predictive even after controlling for this pathology," said Elman.
The findings, wrote the researchers, suggest that low-cost, non-invasive cognitive testing is useful for identifying persons who may be at risk for developing AD, making them ideal candidates for therapeutic intervention and clinical trials.
https://www.sciencedaily.com/releases/2020/02/200214134653.htm