Alzheimer’s affects the networks in the brain that are the cornerstone of our ability to learn and remember. Those networks are dynamic—if the connections, or synapses, aren’t used, they disappear. With Alzheimer’s disease, two proteins in the brain interfere with those synaptic connections: The amyloid protein breaks into fragments that are toxic to the connections and the tau changes into abnormal folds and clusters that are also toxic to the connections. As we lose those connections, we lose our memories, our ability to recall them and our ability to form new ones. The accumulation of those two toxic forms of proteins, in conjunction with inflammation in the brain produced by other causes, including aging, is what breaks down the synapses. We don’t yet know the exact cause for Alzheimer’s or for the accumulation of these toxic proteins. We do know that these processes are influenced by genetics. People with a parent who has Alzheimer’s are at a two-fold risk of developing Alzheimer’s.

Our ability to recall memories naturally slows with age. Our intelligence remains the same, but we may need more time to recall certain things from our memory.

The next stage of memory change is called mild cognitive impairment. With MCI, people other than the person who has MCI may notice a slowing of memory. The loss is not usually substantial enough to interfere with someone’s daily life. 

For some, however, MCI progresses to dementia. Dementia is diagnosed when someone has a loss of function in two or more areas of cognition — such as memory, verbal ability, visuospatial function or judgment— severe enough to significantly affect day-to-day function. There are many potential causes of dementia, but Alzheimer’s is by far the most common. One of the many important jobs for a neurologist is to make the correct diagnosis of the cause of a dementia.    

We are very excited here at Stanford Health Care about our recent selection as one of few National Institutes of Health-funded Alzheimer’s Disease Research Centers (ADRCs) in the country.

The NIH designation comes with a $7.3 million funding award over a five-year period to advance our research in Alzheimer’s disease. With this grant, we will be able to expand the number of clinical trials and research opportunities for our patients. The ADRC will also facilitate joint research projects between neurologists in the center and neuroscientists and other investigators across Stanford University. In addition, the Center includes a program to enhance outreach to make sure that patients from a diverse spectrum of backgrounds and cultures have access to the Center’s research and educational programs.

Stanford neurologist Michael Greicius, MD, PhD, medical director at the Stanford Center for Memory Disorders and the director of the imaging section at the new NIH-funded Alzheimer’s disease Research Center, has recently had great success in developing new imaging methods to examine Alzheimer’s patients. He uses functional MRI and PET scans to track, for the first time, the function of synapses and the accumulation of those extra proteins that interfere with memory function in Alzheimer’s patients.

One of the most powerful substances known to promote the maintenance of synaptic connections is a protein called brain-derived neurotrophic factor, or BDNF. BDNF, like most proteins, would not cross the brain’s protective barrier if it were simply administered as a drug. In its natural protein form, BDNF also would be likely to have side effects. My research team pioneered the development of small molecules that mimic key features of BDNF. These small molecules can get across the brain barrier and prevent degeneration of synapse and other Alzheimer’s related events — without producing the potentially harmful effects of high levels of BDNF. We also know that BDNF decreases with age. By adding back its positive effects, we hope to save those synapses. Studies in mice with Alzheimer’s are going well. Our goal is to complete studies that will allow us to start clinical trials.

Most recently, a research team lead by another Stanford neurologist, Tony Wyss-Coray, PhD, built upon the work of Thomas Rando, MD, PhD, a Stanford expert in the biology of aging, showed that the cognitive abilities of old mice could be improved with an infusion of blood from young mice. Wyss-Coray and his team discovered that the most crucial element of the blood linked to that improvement was a protein in plasma called colony-stimulating factor 2, or CSF2. That’s another very exciting discovery because CSF2 is already FDA-approved for people who have received bone marrow transplants. From many decades of use, we also know that plasma is safe. Inspired by these mouse studies, another Stanford neurologist, Sharon Sha, MD, MS, is running a trial in which blood plasma, obtained from the Stanford Blood Center from  young, healthy volunteers, is being administered to Alzheimer’s patients to determine if that plasma can improve cognition.

In another very exciting research area, neurologist Michael Greicius is discovering genes that appear to protect the brain from accumulations of toxic amyloid and tau. He has identified people well into their 90s whose PET scan show they have normal cognitive function despite having large amounts of amyloid in their brains or the high-risk apoE4 gene generally associated with earlier onset of dementia. Greicius hopes to use his study of these genes to create powerful new preventive treatments, especially for those at particular genetic risk for Alzheimer’s.

We are also looking at new ways to combine some of the medications and treatments we already have to slow the disease process. We know from the example of HIV that although the effects of one drug might be small, a combination of drugs can be highly effective. Our center also collaborates with selected pharmaceutical companies to offer access to trials for study medications that we feel have potential to be beneficial for people with MCI or Alzheimer’s. 

In October 2014, the Stanford Center for Longevity and the Max Planck Institute for Human Development released a statement, signed by nearly 70 researchers, to share our concern that the claims made for these types of games are not supported by substantial scientific evidence. The question is not if you can improve your ability to play a certain computer game but whether that improvement will appear in other tasks you might do. There is no reliable evidence to support such a spillover.

There are also no current reliable and sufficiently sized studies that show a direct link between an increase in cognition by adding coconut water or oil, Omega-3 fatty acids, DHA, vitamin D or turmeric to your diet.

We can’t prevent the influence of aging on the risk of Alzheimer’s. The likelihood of Alzheimer’s increases with age, in part because toxic forms of amyloid protein, tau protein and inflammation in the brain all increase with age. By age 85, four out of 10 people will have been diagnosed with the disease. Nor can we change our genetic risk: About 2 percent of Alzheimer’s appears in people at a young age—in their 40s or 50s—because of their genetics.

Risk for Alzheimer’s can also be influenced by diet, high blood pressure and diabetes. We recommend a Mediterranean diet as a part of an overall plan to reduce your risk of Alzheimer’s, high blood pressure and diabetes.

We have also recently learned that disrupted sleep does not allow the brain to clear amyloids. That knowledge leads us to believe that long-term sleep disruption and the interference with amyloid clearing could also raise your risk of Alzheimer’s.

The most important and research-validated approach to reduce your risk is exercise. Research has shown that 30 minutes a day, five days a week, preferably at a moderate level, reduces the risk for Alzheimer’s.

Unfortunately, there are no currently available FDA-approved medications proven to delay onset or slow progression of the underlying brain degeneration and loss of synaptic connections that occurs in Alzheimer’s disease. There are, however, two groups of FDA-approved medications that can temporarily boost the chemical neurotransmitters at synapses and so produce a modest improvement in cognitive function. We do offer clinical trial use of these medications. They do have side effects. Along with these medications, we strongly encourage physical exercise, a healthy diet and weight, and continued cognitive engagement that could include socializing, hobbies or any other activities that encourage brain function. We work closely with our patients’ primary care physicians to make sure that their patients have optimal levels of B12, vitamin D, thyroid and other substances. We also keep an eye out for any trials, regardless of location, which might benefit our patients. 

Early onset Alzheimer’s is generally defined as dementia that appears before age 60. Early onset Alzheimer’s also appears to be very heritable: People with early onset Alzheimer’s have a 50% chance of passing the gene causing the disorder on to each of their children. We work closely with our neurology genetic counselors to help families learn about the genetics of dementias and to design a plan for genetic testing that is optimal for the specific circumstances of each family. In some cases, people at risk for early onset dementia choose to enter one of the clinical trials that test various drug therapies.