Last month, the Alzheimer’s Association International Conference (AAIC) was held in Washington, D.C. It is the world’s largest forum for Alzheimer’s and dementia research and the Alzheimer’s Association certainly has a lot of research to share this year.
Some of the research highlights include Alzheimer’s drug therapies, women and risk of Alzheimer’s and cognitive decline, and how exercise could be a good treatment method. Keith Fargo, Ph.D., director of scientific programs & outreach for the Alzheimer’s Association, talked to Brandi Walker about these highlights and other information from the meeting.
1. What were the clinical results regarding the drug therapies for Alzheimer’s disease?
Clinical trial results from several studies were presented in July at the Alzheimer’s Association International Conference® 2015 (AAIC® 2015) in Washington, D.C. The studies included findings from Eli Lilly and Company, Roche and Biogen on drugs that target the amyloid brain plaques of Alzheimer’s disease, among other targets.
Eli Lilly and Company presented results of a pooled analysis of data from its negative EXPEDITION and EXPEDITION2 placebo-controlled clinical trials of the experimental anti-amyloid drug solanezumab, suggesting the drug may, in fact, slow the progression of mild Alzheimer’s. The analysis included new data from a two-year extension trial using a “delayed start” statistical approach where participants are randomly assigned to start active treatment or are placed in a “delayed-start” group that receives a placebo for a period of time before being given the active experimental therapy. If the treatment can slow disease progression, both groups will benefit, but the delayed-start group will never “catch up” to the group receiving the treatment for the full duration of the study. The analysis reported at AAIC 2015 showed the delayed starters did not “catch up” and treatment differences in the extension trial between the two groups for cognition and function remained significant through 52 weeks.
Roche researchers presented evidence that gantenerumab produced dose-related reductions of levels of amyloid and tau, a protein that builds up inside cells and produces the hallmark brain tangles of Alzheimer’s. While the reduction of amyloid, measured by brain amyloid PET scans, was not statistically significant, the reduction of tau, measured in cerebrospinal fluid, was. The researchers point out that this is the first study showing clear changes on both these standard markers of Alzheimer’s in people with very early forms of the disease. In December 2014, the company stopped a two-year, Phase 3 clinical trial of the drug in people with early symptoms of Alzheimer’s based on preliminary results indicating the chance of successful completion was very low. However, patients in the study continued to be followed and data collection after the trial stopped was used in the analysis that resulted in the new findings. These findings may prompt the company to launch a new trial of the drug.
Researchers with Biogen presented new results from a Phase 1b clinical trial of aducanumab, which marked the first time an investigational drug for Alzheimer’s showed a statistically significant reduction on amyloid plaque as well as slowed clinical impairment in people with early Alzheimer’s disease. The early results need to be expanded and replicated in larger populations, and Biogen recently launched two Phase 3 trials of the experimental therapy.
2. How much of an impact does school performance at 9 or 10 years old make on being diagnosed later in life?
Early-life cognitive performance may have a great deal of impact on late-life risk for dementia as outlined in the Uppsala Birth Cohort Study conducted by Karolinska Institutet, Stockholm, Sweden. The study followed over 7,000 individuals aged 65 and older for more than 20 years to detect new cases of dementia and also collected data on their childhood cognitive abilities. Researchers saw the lowest dementia risk (39 percent reduction) in the group who had both higher childhood school performance and high occupational complexity with data, while the dementia risk was elevated 21 percent in people who were in the lowest 20 percent of childhood school grades in this population. Another study reported at AAIC 2015 by researchers at the Karolinska Institutet found dementia risk was elevated more than 50 percent in individuals over 75 with the lowest 20 percent of early-life school grades, even if they had more formal education or a job requiring significant complexity.
Given the growing evidence that people can reduce their risk of cognitive decline, the Alzheimer’s Association recently shared 10 Ways to Love Your Brain, tips that may help lessen the chance of cognitive decline as we age. The suggestions include engaging in regular cardiovascular exercise that elevates your heart rate, getting more formal education, and quitting smoking. The complete list can be found at alz.org.
3. Why are there more senior women living with this illness than men?
Almost two-thirds of American seniors living with Alzheimer’s disease are women. This may be accounted for, in whole or in part, by the fact that women tend to live longer and therefore are more likely to develop Alzheimer’s or dementia. That said, recent research suggests that there may also be biological or genetic factors, or even different life experiences, at play that cause women to develop Alzheimer’s more than men. Some evidence also suggests that interaction between the APOE-e4 genotype (the best known genetic risk factor for Alzheimer’s disease) and the sex hormone estrogen may lead to the development of Alzheimer’s.
Interestingly, at AAIC 2015, research was presented that suggests that women with mild cognitive impairment (MCI) have two times faster decline in cognition than men with MCI. In addition, women decline more dramatically than men in cognition, function and brain size after surgery and general anesthesia, according to another study reported at AAIC 2015. Alzheimer’s Association Expert discusses new research from conference
4. Tell me more about these new advances in early detection of Alzheimer’s.
Early detection of Alzheimer’s related symptoms is critically important for individuals with the disease and their families, and for clinical trials. Two studies from AAIC 2015 showed that an excess of certain proteins, such as neurogranin, in cerebrospinal fluid are strong predictors of Alzheimer’s. However, the accuracy of these predictions is stronger when they are considered together with other diagnostic tools, such as memory tests or MRI brain scans.
A third study from AAIC 2015 showed new ways of creating images of inflammation in the brain with PET scans could one day be used to identify treatments that protect the brain. Lastly, a small study suggests it could be possible to detect Alzheimer’s-like changes in saliva through analysis of proteins it contains, but additional studies are needed in larger, more diverse populations before this can be considered a viable diagnostic tool.
5. What were the medical results regarding the aerobic exercise trials?
We know that regular physical activity may reduce the risk of cognitive decline, Alzheimer’s disease and other dementias. Three new research studies reported at AAIC 2015 demonstrated the value of moderate to high intensity aerobic exercise for people with Alzheimer’s and other dementias, finding that this type of exercise may help them live better with the disease.
One study of 200 people with Alzheimer’s age 50-90 showed that study participants who completed a 4-month high intensity aerobic exercise program had fewer psychiatric symptoms, such as anxiety, irritability and depression. Those who exercised hardest also had improvements on mental speed and attention. A second study of moderate-to-high intensity aerobic exercise in 65 sedentary adults 55-89 years old with mild cognitive impairment found that exercise may reduce levels of abnormal proteins in cerebrospinal fluid and increase blood flow in the brain’s memory and processing centers. This aerobic exercise program appears to improve attention, planning and organizing abilities. Finally, a six-month study of 71 adults 56-96 years old with vascular cognitive impairment found that participating in a supervised aerobic exercise program was associated with improvements in memory and attention.
It is important to note that these three studies were not simply looking back at people who had exercised more during their lives, but rather were randomized, controlled trials of exercise as a therapeutic intervention.
These studies highlight the potential value of non-drug therapies for Alzheimer’s and other dementias and remind us that research ought to adamantly pursue multiple approaches to Alzheimer’s therapy and prevention.
For more information on the Alzheimer’s Association, visit http://www.alz.org/.