Aerobic exercise training linked to enhanced brain function
Regular aerobic exercise may decrease the likelihood of developing Alzheimer's disease
February 3, 2020
Science Daily/IOS Press
Individuals at risk for Alzheimer's disease (AD) because of family history or genetic predisposition who engaged in six months of aerobic exercise training improved their brain glucose metabolism and higher-order thinking abilities (e.g., planning and mental flexibility) called executive function; these improvements occurred in conjunction with increased cardiorespiratory fitness. The results of this study are published in a special issue of Brain Plasticity devoted to Exercise and Cognition.
Drugs currently available to treat AD have limited therapeutic capacity. At a time when both the human and monetary costs of the disease are projected to rise dramatically in the coming decades, there is a critical need to provide individuals with readily-deployable strategies that can decrease the likelihood of acquiring the disease or slow its progression. Researchers therefore investigated whether exercise training in asymptomatic individuals harboring risk for AD improves markers associated with AD.
"This study is a significant step toward developing an exercise prescription that protects the brain against AD, even among people who were previously sedentary," explained lead investigator Ozioma C. Okonkwo, PhD, of the Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health.
The study investigated 23 cognitively normal, relatively young older adults with a family history or genetic risk for AD. All patients had a sedentary lifestyle. They underwent a battery of assessments, including cardiorespiratory fitness testing, measurement of daily physical activity, brain glucose metabolism imaging (a measure of neuronal health), and cognitive function tests.
Half of the participants were randomly assigned to receive information about maintaining an active lifestyle but no further intervention. The other half participated in a moderate intensity treadmill training program with a personal trainer, three times per week for 26 weeks.
Compared to the participants maintaining their usual level of physical activity, individuals assigned to the active training program improved their cardiorespiratory fitness, spent less time sedentary after the training program ended, and performed better on cognitive tests of executive functioning (but not episodic memory). Executive function, an aspect of cognition that is known to decline with the progression of AD, comprises the mental processes enabling individuals to plan, focus attention, remember instructions, and juggle multiple tasks successfully. The participants' improved cardiorespiratory fitness was associated with increased brain glucose metabolism in the posterior cingulate cortex, an area of the brain linked to AD.
"This research shows that a lifestyle behavior -- regular aerobic exercise -- can potentially enhance brain and cognitive functions that are particularly sensitive to the disease. The findings are especially relevant to individuals who are at a higher risk due to family history or genetic predisposition," noted Dr. Okonkwo. The lead author on the study, Max Gaitán, MEd, of the Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, remarked that "an important next step would be to conduct a larger, more definitive, study. If these findings are replicated, they would have a tremendous impact on quality of later life, providing individuals with more years of independent living, active engagement with loved ones, and building memories."
https://www.sciencedaily.com/releases/2020/02/200203104450.htm
Exercise offers protection against Alzheimer's
July 16, 2019
Science Daily/Massachusetts General Hospital
Higher levels of daily physical activity may protect against the cognitive decline and neurodegeneration (brain tissue loss) from Alzheimer's disease (AD) that alters the lives of many older people, researchers from Massachusetts General Hospital (MGH) have found. In a paper in JAMA Neurology, the team also reported that lowering vascular risk factors may offer additional protection against Alzheimer's and delay progression of the devastating disease. The findings from this study will be presented at the Alzheimer's Association International Conference (AAIC) in Los Angeles by the first author of the study, Jennifer Rabin, PhD, now at the University of Toronto, Sunnybrook Research Institute.
"One of the most striking findings from our study was that greater physical activity not only appeared to have positive effects on slowing cognitive decline, but also on slowing the rate of brain tissue loss over time in normal people who had high levels of amyloid plaque in the brain," says Jasmeer Chhatwal, MD, PhD of the MGH Department of Neurology, and corresponding author of the study. The report suggests that physical activity might reduce b-amyloid (Ab)-related cortical thinning and preserve gray matter structure in regions of the brain that have been implicated in episodic memory loss and Alzheimer's-related neurodegeneration.
The pathophysiological process of AD begins decades before clinical symptoms emerge and is characterized by early accumulation of b-amyloid protein. The MGH study is among the first to demonstrate the protective effects of physical activity and vascular risk management in the "preclinical stage" of Alzheimer's disease, while there is an opportunity to intervene prior to the onset of substantial neuronal loss and clinical impairment. "Because there are currently no disease-modifying therapies for Alzheimer's disease, there is a critical need to identify potential risk-altering factors that might delay progression of the disease," says Chhatwal.
The Harvard Aging Brain Study at MGH assessed physical activity in its participants -- 182 normal older adults, including those with elevated b-amyloid who were judged at high-risk of cognitive decline -- through hip-mounted pedometers which counted the number of steps walked during the course of the day.
"Beneficial effects were seen at even modest levels of physical activity, but were most prominent at around 8,900 steps, which is only slightly less than the 10,000 many of us strive to achieve daily," notes co-author Reisa Sperling, MD, director of the Center for Alzheimer's Research and Treatment, Brigham and Women's Hospital and Massachusetts General Hospital and co-principal investigator of the Harvard Aging Brain Study.
Interventional approaches that target vascular risk factors along with physical exercise have added beneficial properties, she adds, since both operate independently. Vascular risk factors measured by the researchers were drawn from the Framingham Cardiovascular Disease Risk Score Calculator, and include age, sex, weight, smoking/non-smoking, blood pressure, and whether people are on treatment for hypertension.
Through ongoing studies MGH is working to characterize other forms of physical activity and lifestyle changes that may help retard the progress of Alzheimer's disease. "Beta amyloid and tau protein build-up certainly set the stage for cognitive impairment in later age, but we shouldn't forget that there are steps we can take now to reduce the risk going forward -- even in people with build-up of these proteins," says Chhatwal. "Alzheimer's disease and the emergence of cognitive decline is multifactorial and demands a multifactorial approach if we hope to change its trajectory."
https://www.sciencedaily.com/releases/2019/07/190716193543.htm
Relative risk of Alzheimer's between men and women: Record corrected
Women genetically predisposed to Alzheimer's are more susceptible than men between ages 65 and 75, researchers discover
August 28, 2017
Science Daily/University of Southern California
White women whose genetic makeup puts them at higher risk for Alzheimer's disease are more likely than white men to develop the disease during a critical 10-year span in their lives. The findings from one of the world's largest big-data studies on Alzheimer's counter long-held beliefs about who is at greatest risk for the disease and when, suggesting new avenues for clinical trials.
The findings from one of the world's largest big-data studies on Alzheimer's counter long-held beliefs about who is at greatest risk for the disease and when, suggesting new avenues for clinical trials.
Study results show genetically vulnerable 55- to 85-year-old white men and women have the same odds of developing the memory-erasing disease. One exception: From their mid-60s to mid-70s, these women still face significantly higher risk. That may provide clues to disease causes and potential interventions among these women.
"Our discovery is important because it highlights how clinical trials could be weighted toward women -- a susceptible part of the population -- to help scientists more rapidly identify effective drug interventions to slow or cure Alzheimer's," said Arthur Toga, director of the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine -- among the nation's leaders in innovative scientific discovery.
The study was published Aug. 28 in the Journal of the American Medical Association Neurology. It included data from 57,979 North Americans and Europeans in the Global Alzheimer's Association Interactive Network (GAAIN). This big-data project provides scientists around the world with shared data and sophisticated analysis tools to address a disease that makes up about 65 percent of the 47 million cases of dementia worldwide.
Times -- and data -- have changed
The results contradict a seminal 20-year-old study that found women with one copy of ApoE4, a gene variant linked to Alzheimer's, were diagnosed with the disease 50 percent more often than men with the same genetic profile.
The findings presented in the USC-led study expand the number of participant data by ninefold and indicate the critical decade falls between 65 and 75, more than 10 years after the start of menopause. Previous studies in animals and humans have reported a relationship between ApoE4, menopause and cognitive decline.
"So much work has been dependent on one 1997 finding, but with tools like GAAIN, we now have the ability to reinvestigate with increased statistical power," Toga said.
The new findings are significant because almost two-thirds of the more than 5 million Americans now living with Alzheimer's disease are women, according to the Alzheimer's Association.
Many attribute the imbalance in disease risk to the fact that women, on average, live longer than men. However, a growing body of evidence suggests other reasons also contribute to the difference. For instance, men have higher rates of heart disease and stroke. So, men who live longer may be healthier than women of the same age and may face less risk of developing Alzheimer's, according to the USC-led study.
In the future, doctors who want to prevent Alzheimer's may intervene at different ages for men and women, said Judy Pa, co-author of the study and an assistant professor of neurology at the USC Stevens Neuroimaging and Informatics Institute.
"Menopause and plummeting estrogen levels, which on average begins at 51, may account for the difference," Pa said. "However, scientists still don't know what is responsible. Researchers need to study women 10, 15 or even 20 years before their most vulnerable period to see if there are any detectable signals to suggest increased risk for Alzheimer's in 15 years."
Worry less, work out more
Only some women are at increased risk of developing Alzheimer's in their mid-60s to mid-70s compared to men. To find out, women could have their DNA analyzed. However, Pa cautions that genetic testing for the ApoE4 variant is no crystal ball.
"There is controversy in terms of whether people should know their ApoE status because it is just a risk factor," Pa said. "It doesn't mean you're going to get Alzheimer's disease. Even if you carry two copies of ApoE4, your chances are greatly increased, but you could still live a long life and never have symptoms."
Even if some women discover they are at heightened risk, they can improve their odds by making life changes.
"Get more exercise. Work out your mind, especially in old age," Pa said. "Pick up hobbies that are cognitively or physically challenging. Reduce processed sugar intake because it's linked to obesity, which is associated with many chronic diseases."
More minorities please
Alzheimer's disease is the fifth-leading cause of death for Americans 65 and older, but it may one day outpace the nation's top two killers -- heart disease and cancer. Alzheimer's-related deaths increased by nearly 39 percent between 2000 and 2010 while heart disease-related deaths declined 31 percent and cancer deaths fell 32 percent, according to the Centers for Disease Control and Prevention.
Because Alzheimer's disease has a huge impact on lifelong health, USC has more than 70 researchers dedicated to the prevention, treatment and potential cure of the memory-erasing disease. Big data projects like this require experts across disciplines -- computer science, biology, pathophysiology, imaging and genetics -- to coordinate.
For this study, the researchers examined data from 27 different studies that assessed participants' ApoE gene variation, as well as characteristics such as sex, race, ethnicity, diagnosis (normal, mild cognitive impairment or Alzheimer's disease) and age at diagnosis.
The records of nearly 58,000 people were scrutinized. Meta-analyses were performed on 31,340 whites who received clinical diagnoses sometime between ages 55 and 85.
The proportion of minorities was so small that analysts could not draw statistically significant conclusions about their disease risk. Because of this, the study focused on whites only.
"Most of the archives around the world have insufficient numbers of underrepresented groups," Toga said. "One of the take-home messages from our study is people of all races and ethnicities need to be involved in Alzheimer's clinical trials because this disease is a problem that affects all of us."
The current findings need to be confirmed in more diverse study populations.
USC is working to build more diverse population studies related to Alzheimer's. Established in 1984, the Alzheimer Disease Research Center at the Keck School of Medicine reaches out to communities in the greater Los Angeles area to educate the city's diverse population about Alzheimer's and the clinical trials they might be interested in joining. Previous studies, for example, have focused on Latinos.
It's 2017: Time to focus on women
Historically, women have not been adequately represented in clinical trials, especially in studies on heart disease. Women need to be represented equally to men -- or even overrepresented, Pa said.
"The bottom line is women are not little men," Pa said. "A lot more research needs to target women because gender-specific variations can be so subtle that scientists often miss them when they control for gender or use models to rule out gender differences. Most research today is ignoring a big part of the equation."
The particulars
The study was made possible because of lead author Scott Neu, a leader in the development of a federated approach to analyzing metadata and assistant professor of research at the Laboratory of Neuro Imaging at the Keck School of Medicine.
"GAAIN -- the free resource we created in conjunction with the Alzheimer's Association -- allows anyone to explore data sets around the world and conduct preliminary analyses to test scientific hypotheses," Neu said. "Our goal is to connect scientists with those who have collected data to create new collaborations to further research and understanding of Alzheimer's disease."
Analysts excluded people with a history of stroke, cerebrovascular disease, abnormal proteins that contribute to Parkinson's disease and dementia, gene mutations leading to higher levels of toxic amyloid brain plaques and any known neurological diseases.
Scientists did not adjust for known Alzheimer's risk factors such as education, family history of Alzheimer's or dementia because that information was not provided in all data sets. They also were unable to adjust for sex-dependent differences such as cigarette smoking, hormonal changes with age and alcohol usage.
https://www.sciencedaily.com/releases/2017/08/170828124531.htm
Exercise may help prevent brain damage caused by Alzheimer's disease
August 15, 2011
Science Daily/Elsevier
Regular exercise could help prevent brain damage associated with neurodegenerative diseases like Alzheimer's, according to new research.
"Exercise allows the brain to rapidly produce chemicals that prevent damaging inflammation," said Professor Jean Harry, who led the study at the National Institute of Environmental Health Sciences in the United States. "This could help us develop a therapeutic approach for early intervention in preventing damage to the brain."
Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults.
The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.
http://www.sciencedaily.com/releases/2011/08/110815095727.htm