Alzheimer's Risk Factors, Genetics, Family History and Prevention
“I don’t know why I can’t remember words lately,” my maternal grandmother said to my mother. Grandma Ben (shown here at her college graduation in 1924) was then in her early 80’s, brisk and competent. Around the same time, my paternal grandmother (right) started getting lost while driving around our small town. “Kilo,” as we called her, was in her early 70’s. And when my father (below, on the Pamlico River with his dog Beau) was in his late 60’s, he too had trouble finding words. They all went on to develop dementia. So it isn’t surprising I had a personal interest in a presentation called “Family History as a Risk Factor for Alzheimer’s” at the Wisconsin State Conference on Alzheimer’s Disease and Related Disorders earlier this month. The talk was given by Dr. Mark Sager, Director of the Wisconsin Alzheimer’s Institute at the University of Wisconsin. For early onset Alzheimer’s disease, family history is a huge risk factor. But the majority of people who develop dementia do so later in life, and it’s not clear what role family history plays in these cases. One genetic variant (APOE4) is associated with increased risk of late onset Alzheimer’s, and researchers are working to confirm the risk associated with another gene, SORL1. But these weakly associated genes don’t allow us to predict with any accuracy who will develop Alzheimer’s. Are there other inherited or family risk factors? This isn’t clear, says Dr. Sager. “We know nothing about the adult children of Alzheimer’s disease - we don’t really understand the risk.” By tracking these adult children through a program called WRAP (Wisconsin Registry for Alzheimer’s Prevention), Dr. Sager and his colleagues hope to address this knowledge gap. The average age at enrollment of the more than 1000 WRAP volunteers is 53, much younger than when the first symptoms of Alzheimer’s typically appear. Why study people before they develop dementia? “Alzheimer’s is labeled an old person’s disease because the brain is so resilient that the disease manifests when people are in their 60’s, 70’s and 80’s,” says Dr. Sager. “But actually, the brain begins to fail much earlier.” Scientists hope that within a few years, Alzheimer’s will be more like heart disease in that we will be able to identify who is at risk, and begin treatment before symptoms appear. “The presence of symptoms means the disease is at an advanced stage,” Dr. Sager says. “We want to intervene before that.” What does data from the first wave of testing in the WRAP program show? On average, the neuropsychological test scores of the adult children of Alzheimer’s are the same as those of volunteers whose parents didn’t have the disease. But even though they have no apparent cognitive problems, the brains of volunteers whose parents had Alzheimer’s seem to work differently. During functional MRIs, participants with a family history of Alzheimer’s show less activity in the part of the brain called the hippocampus when viewing new items. A second wave of testing, funded by a grant from the U.S. National Institutes of Health, will determine if the Alzheimer’s children’s thinking and memory has declined over the four year interval between evaluations. These tests will include PET scans using the new Pittsburgh Compound B imaging to map amyloid deposits in the volunteers’ brains. WRAP data is also being used to study risk factors besides family history, including: - previous surgeries (often associated with post-operative memory problems) - high cholesterol (and the use of statins) - hormonal status (along with the use of hormone therapy). Even before we understand how to prevent or delay Alzheimer’s, the staff at WRAP is developing a pilot study of interventions based on the available research. Study volunteers who develop Mild Cognitive Impairment will be offered these interventions in an attempt to slow or prevent further decline. Interventions will probably involve the lifestyle factors that research has shown may lower the risk for Alzheimer’s, such as cognitive and leisure activities, moderate alcohol consumption and physical exercise, as well as reducing psychological stress or untreated depression. Dr. Sager and his colleagues are also following the research on substances that may delay onset or slow progression of Alzheimer’s. It’s too early to recommend them for prevention, and some have bad side effects. You should check with your doctor before considering any of these treatments on Dr. Sager’s watch list: - estrogen - ginkgo [but many formulations contain contaminants – I’ll write more about this soon] - medicines that lower blood pressure - folic acid - non-steroidal anti-inflammatory drugs - Dr. Sager notes side effects including kidney damage have caused trials of these medicines for Alzheimer’s to be discontinued. - statins - trials are ongoing - selegiline [I plan to write more about this over the summer] - vitamin E - supplements are controversial, so it’s best to try to get this vitamin from foods, Dr. Sager says. - cholinesterase inhibitors [but there’s not enough evidence that these help before symptoms appear]. Want to help? You don’t have to live in Wisconsin to volunteer for WRAP, but you must be able to travel to Madison for testing every four years. People whose parents did not have Alzheimer’s are also needed for comparison. If you’re interested, contact Janet Rowley at 608-829-3306 or [email protected] If all of us with family histories of dementia can work with researchers in programs like WRAP, maybe our children and grandchildren will never experience the first symptoms of a failing brain.
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