What scientists do know is that the two copies of genes inherited from parents play a role in determining the level of risk of developing diseases like Alzheimer’s. For example, people with one copy of APOE4, a variation of the APOE gene responsible for regulating cholesterol in our blood, are two or three times more likely to develop the disease than someone with other com- binations of APOE genes. Someone with two copies of the allele, i.e. one from both parents, can be 12 times more likely to get Alzheimer’s. Both carriers are also likely to develop the disease “early,” in life (if they develop it at all,) meaning before the age of 65. A roundup of 20 articles published in 2012 found that only 11 percent of Ameri- cans diagnosed with Alzheimer’s had two copies of APOE4. Just over half of those diagnosed with the disease had one copy. The Alzheimer’s Association strongly


cautions people to think carefully before get- ting tested. It urges people to lead healthy lifestyles regardless of whether they have the gene. “Today, not only is there no effective


pharmaceutical intervention to slow or stop Alzheimer’s, there is no definitive research on how to prevent the disease,” according to the association in an official position paper. “Things to think about when consider-


ing genetic testing for Alzheimer's disease may include how it could affect one's em- ployment, health insurance, and long-term care insurance,” it advises. “People should receive genetic counseling before a test is ordered and when the results are obtained. A genetic counselor may be found through the National Society of Genetic Counselors (nsgc.org)."


The Murky World of Diagnosis and Disease Management The genetic testing quandary points to the current reality that neurodegenerative diseas- es like Alzheimer’s differ from heart disease and cancer—America’s other top killer dis- eases—in that primary care physicians don’t yet have standardized blood tests, scans, or tissue sampling routines to check whether a patient has developed the disease. By the time a person manifests symptoms and asks for a cognitive test from either a primary care physician or a neurologist, the harm- ful proteins might have been accumulating undetected, killing neurons, and shrinking a person’s brain for up to 20 years.


The scientific community is working hard


on developing tests to detect and monitor the extent of those accumulations in our brains and the damage they’re doing. For now, the community is proposing to use the tests and the testing framework for research purposes. The researchers want to use the framework to develop drugs to treat the various forms of dementia. But the whole process could take several years to reach fruition. “Just consider any other chronic disease,


like heart failure, or hepatitis, or kidney failure, or HIV infection,” said Stanford’s Montine. “Just imagine trying to manage those diseases upon which you had no labo- ratory tests upon which to base your clinical management.” It sounds as if it’s a bit like driving blindfold-


ed: You might be able to hear things around you and feel the motion, but you can’t see any markers like the road, road signs or road markers to guide you to your destination. To make better use of all the emerging


discoveries about the biology of the neuro- degenerative diseases, the medical commu- nity needs better standardized road signs – or


tors can test the efficacy of drug treatments or lifestyle interventions at the diseases’ vari- ous stages. Ultimately, in an ideal world and after proving their methodologies across populations of thousands of people, doctors ultimately would be able to tell whether an individual is developing dangerous levels of proteins in the brain before symptoms like impaired memories and language loss mani- fest themselves, and provide a treatment. “To answer that sort of question, you still


have to have some laboratory-based testing to determine who has the disease, and who doesn't, and how quickly someone is pro- gressing,” explained Montine. “You need to be able to determine how effective your [disease] management plan is, or isn’t.” Washington University’s Raji agrees, and


as a radiologist, he thinks MRI techniques are well positioned to support these determina- tions. He and a group of colleagues recently conducted a study suggesting that MRIs could predict the onset of dementia 2.6 years before the symptoms manifest themselves. Increasingly sophisticated MRI imaging techniques can detect changes in patterns in


“More and more research is coming out about physical activity and movement delaying disease and improving cognitive outcomes. We can build that into our days in simple ways. For instance, when we’re doing activities, our teams and the residents can get up and walk to an- other area of the neighborhood to do the next activity.”


biomarkers. The proposed methods include magnetic resonance imaging or positron emission tomography (PET) scans, and/ or cerebrospinal fluid samples to detect the protein accumulations. Researchers are also working on developing blood tests. The goal is to create standardized terminologies and tests for the research community around the globe, so that they’re all working on the same track when developing treatments. They hope that this will enable them to tailor personalized treatment and preventative solutions. The general idea is to enable researchers


to gain more precise information about who is developing a neurodegenerative disease, and identify the stage of the disease so doc-


people’s brain matter and volume over time. Radiologists observing these changes can either rule out certain disease possibilities by observing different areas of individuals’ brains and whether they’re at normal sizes. For example, Raji and his colleagues pub- lished a paper in 2009 that linked increas- ing body mass indices to shrinking brains. The 94 elderly subjects showed no outward disease symptoms, yet MRI scans revealed that their brains had shrunk in an unhealthy fashion over five years. Raji and his colleagues later also tested


the opposite hypothesis—that cardiovascu- lar and general fitness can actually increase brain volume and health. They found that


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