Cognition and gait speed often decline together
Mexican Americans at higher risk
May 5, 2020
Science Daily/University of Texas Health Science Center at San Antonio
Measures of cognition and gait speed largely paralleled each other in a San Antonio study of 370 participants that included 9½ years of follow-up. One-fifth of participants were classified into a cognitive and physical vulnerability group. Mexican American participants were almost four times more likely than European Americans to be in the cognitive and physical vulnerability group.
Do thinking and walking go hand in hand in determining the health course of senior adults? A study published by UT Health San Antonio researchers found that, indeed, the two functions often parallel each other in determining a person's health trajectory.
The researchers analyzed data from 370 participants in the San Antonio Longitudinal Study of Aging (SALSA) and found that they grouped into three distinct trajectories. These classifications were based on the participants' changes on a cognitive measure and a gait speed task over an average of 9½ years:
Stable cognition and gait class (65.4% of the participants).
Cognitive and physical vulnerability class (22.2%).
Physical vulnerability class (12.4%).
"In our community-based sample of Mexican American and European American older adults aged 65 to 74 years old at baseline, the majority of individuals began the study with higher scores in both domains, cognition and gait speed. During follow-up, this group demonstrated resilience to age-related declines and continued to be functionally independent," said study senior author Helen Hazuda, Ph.D., professor in UT Health San Antonio's Long School of Medicine and the principal investigator of SALSA.
"In contrast, one-fifth of individuals began the study with lower scores in cognition and gait speed. They experienced deterioration in each domain during the follow-up period," Dr. Hazuda said.
The third group of individuals, termed the physical vulnerability class, demonstrated stable cognition throughout the study, but their gait speed slowed over time.
2 effects, 1 root?
Cognition was assessed using English or Spanish versions of the Folstein Mini-Mental State Examination, a 30-item tool that assesses orientation to time and place, attention, recall, language and other aspects. Gait speed was measured with a timed 10-foot walk.
"For most of the population we studied, changes in cognition and gait speed were parallel, which suggests shared mechanisms," said Mitzi M. Gonzales, Ph.D., lead author of the study and a neuropsychologist with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, which is part of UT Health San Antonio.
Cognition and gait speed may be altered by blood vessel disease, brain tissue insults, hormone regulation, and abnormal deposits of amyloid beta and tau proteins in the brain, Dr. Gonzales said. Amyloid beta and tau deposits are well-known indicators of Alzheimer's disease but may impact gait, too.
"Abnormal protein deposition promotes neurodegeneration and synaptic loss, which may induce dysfunction in brain regions governing cognition and gait," said study coauthor Sudha Seshadri, M.D., professor of neurology in the Long School of Medicine and director of the Biggs Institute. "Another possibility is damage to white matter in regions integral to both cognition and gait coordination."
Groundbreaking San Antonio research
SALSA investigators led by Dr. Hazuda launched the study in 1992 and completed the baseline examination in 1996. Follow-up examinations were conducted at 18-month intervals between 2000 and 2005.
Among the 370 participants in this new analysis, 182 were Mexican American and 188 were European American. The Mexican American participants were almost four times more likely than European Americans to be in the cognitive and physical vulnerability class, even after statistical adjustment for educational attainment, income and chronic medical conditions, Dr. Gonzales said.
Prevalence of a key risk factor in this group, diabetes, was significantly higher in Mexican Americans (23%) than in European Americans (7%). Diabetes was associated with a 4½ times higher likelihood of being part of the cognitive and physical vulnerability class.
Poor start, poor course
Individuals who entered the study with poorer cognition and slower gait speed went on to decline in both domains at an accelerated pace through the years of follow-up, Dr. Hazuda said.
"In this at-risk group, we observed steeper rates of decline over and above the low starting point," Dr. Hazuda said. "This suggests that preventive efforts should ideally target young and middle-aged adults in which there is still time to intervene to alter the trajectories."
Overall, individuals in the cognitive and physical vulnerability class and the physical vulnerability class had a five- to sevenfold increased risk of mortality in comparison to the stable cognition and gait class.
https://www.sciencedaily.com/releases/2020/05/200505121717.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
Scientists propose new theory on Alzheimer's, amyloid connection
April 23, 2019
Science Daily/Florida Atlantic University
Worldwide, 50 million people are living with Alzheimer's disease and other dementias. According to the Alzheimer's Association, every 65 seconds someone in the United States develops this disease, which causes problems with memory, thinking and behavior.
It has been more than 100 years since Alois Alzheimer, M.D., a German psychiatrist and neuropathologist, first reported the presence of senile plaques in an Alzheimer's disease patient brain. It led to the discovery of amyloid precursor protein that produces deposits or plaques of amyloid fragments in the brain, the suspected culprit of Alzheimer's disease. Since then, amyloid precursor protein has been extensively studied because of its association with Alzheimer's disease. However, amyloid precursor protein distribution within and on neurons and its function in these cells remain unclear.
A team of neuroscientists led by Florida Atlantic University's Brain Institute sought to answer a fundamental question in their quest to combat Alzheimer's disease -- "Is amyloid precursor protein the mastermind behind Alzheimer's disease or is it just an accomplice?"
Mutations found in amyloid precursor protein have been linked to rare cases of familial Alzheimer's disease. Although scientists have gained a lot knowledge about how this protein turns into amyloid plaques, little is known about its native function in neurons. In the case of more common sporadic Alzheimer's disease, the highest genetic risk factor is a protein that is involved in cholesterol transportation and not this amyloid precursor protein. Moreover, various clinical trials designed to address Alzheimer's disease by minimizing amyloid plaque formation have failed, including one from Biogen announced last month.
In a study published in the journal Neurobiology of Disease, Qi Zhang, Ph.D., senior author, an investigator at the FAU Brain Institute, and an assistant research professor in FAU's Schmidt College of Medicine, along with collaborators from Vanderbilt University, tackle this Alzheimer's disease mystery by devising a multi-functional reporter for amyloid precursor protein and tracking the protein's localization and mobility using quantitative imaging with unprecedented accuracy.
For the study, Zhang and collaborators genetically disrupted the interaction between cholesterol and amyloid precursor protein. Surprisingly, by disengaging the two, they discovered that this manipulation not only disrupts the trafficking of amyloid precursor protein but also messes up cholesterol distribution at the neuronal surface. Neurons with an altered distribution of cholesterol exhibited swollen synapses and fragmented axons and other early signs of neurodegeneration.
"Our study is intriguing because we noticed a peculiar association between amyloid precursor protein and cholesterol that resides in the cell membrane of synapses, which are points of contact among neurons and the biological basis for learning and memory," said Zhang. "Amyloid precursor protein may just be one of the many accomplices partially contributing to cholesterol deficiency. Strangely, the heart and brain seem to meet again in the fight against bad cholesterol."
Given the broad involvement of cholesterol in almost all aspects of neurons' life, Zhang and collaborators have proposed a new theory about the amyloid precursor protein connection in Alzheimer's disease, especially in the surface of those tiny synapses, which triggers neurodegeneration.
"Although still in early stages, this cutting-edge research by Dr. Zhang and his collaborators at Vanderbilt University may have implications for the millions of people at risk for or suffering with Alzheimer's disease," said Randy D. Blakely, Ph.D., executive director of the FAU Brain Institute and a professor of biomedical science in FAU's Schmidt College of Medicine. "The number of people in Florida alone who are age 65 and older with Alzheimer's disease is expected to increase 41.2 percent by 2025 to a projected 720,000, highlighting the urgency of finding a medical breakthrough."
Locally, Alzheimer's disease affects 11.5 percent of Medicare beneficiaries in Palm Beach County and 12.7 percent of Medicare beneficiaries in Broward County (a nearly 18 percent increase over national average).
According to the Alzheimer's Association, Florida is number one in per capita cases of Alzheimer's disease in the U.S.
https://www.sciencedaily.com/releases/2019/04/190423113951.htm
Eating mushrooms may reduce the risk of cognitive decline
March 12, 2019
Science Daily/National University of Singapore
Researchers found that seniors who consume more than two standard portions of mushrooms weekly may have 50 percent reduced odds of having mild cognitive impairment.
A team from the Department of Psychological Medicine and Department of Biochemistry at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS) has found that seniors who consume more than two standard portions of mushrooms weekly may have 50 per cent reduced odds of having mild cognitive impairment (MCI).
A portion was defined as three quarters of a cup of cooked mushrooms with an average weight of around 150 grams. Two portions would be equivalent to approximately half a plate. While the portion sizes act as a guideline, it was shown that even one small portion of mushrooms a week may still be beneficial to reduce chances of MCI.
"This correlation is surprising and encouraging. It seems that a commonly available single ingredient could have a dramatic effect on cognitive decline," said Assistant Professor Lei Feng, who is from the NUS Department of Psychological Medicine, and the lead author of this work.
The six-year study, which was conducted from 2011 to 2017, collected data from more than 600 Chinese seniors over the age of 60 living in Singapore. The research was carried out with support from the Life Sciences Institute and the Mind Science Centre at NUS, as well as the Singapore Ministry of Health's National Medical Research Council. The results were published online in the Journal of Alzheimer's Disease on 12 March 2019.
Determining MCI in seniors
MCI is typically viewed as the stage between the cognitive decline of normal ageing and the more serious decline of dementia. Seniors afflicted with MCI often display some form of memory loss or forgetfulness and may also show deficit on other cognitive function such as language, attention and visuospatial abilities. However, the changes can be subtle, as they do not experience disabling cognitive deficits that affect everyday life activities, which is characteristic of Alzheimer's and other forms of dementia.
"People with MCI are still able to carry out their normal daily activities. So, what we had to determine in this study is whether these seniors had poorer performance on standard neuropsychologist tests than other people of the same age and education background," explained Asst Prof Feng. "Neuropsychological tests are specifically designed tasks that can measure various aspects of a person's cognitive abilities. In fact, some of the tests we used in this study are adopted from commonly used IQ test battery, the Wechsler Adult Intelligence Scale (WAIS)."
As such, the researchers conducted extensive interviews and tests with the senior citizens to determine an accurate diagnosis. "The interview takes into account demographic information, medical history, psychological factors, and dietary habits. A nurse will measure blood pressure, weight, height, handgrip, and walking speed. They will also do a simple screen test on cognition, depression, anxiety," said Asst Prof Feng.
After this, a two-hour standard neuropsychological assessment was performed, along with a dementia rating. The overall results of these tests were discussed in depth with expert psychiatrists involved in the study to get a diagnostic consensus.
Mushrooms and cognitive impairment
Six commonly consumed mushrooms in Singapore were referenced in the study. They were golden, oyster, shiitake and white button mushrooms, as well as dried and canned mushrooms. However, it is likely that other mushrooms not referenced would also have beneficial effects.
The researchers believe the reason for the reduced prevalence of MCI in mushroom eaters may be down to a specific compound found in almost all varieties. "We're very interested in a compound called ergothioneine (ET)," said Dr Irwin Cheah, Senior Research Fellow at the NUS Department of Biochemistry. "ET is a unique antioxidant and anti-inflammatory which humans are unable to synthesise on their own. But it can be obtained from dietary sources, one of the main ones being mushrooms."
An earlier study by the team on elderly Singaporeans revealed that plasma levels of ET in participants with MCI were significantly lower than age-matched healthy individuals. The work, which was published in the journal Biochemical and Biophysical Research Communications in 2016, led to the belief that a deficiency in ET may be a risk factor for neurodegeneration, and increasing ET intake through mushroom consumption might possibly promote cognitive health.
Other compounds contained within mushrooms may also be advantageous for decreasing the risk of cognitive decline. Certain hericenones, erinacines, scabronines and dictyophorines may promote the synthesis of nerve growth factors. Bioactive compounds in mushrooms may also protect the brain from neurodegeneration by inhibiting production of beta amyloid and phosphorylated tau, and acetylcholinesterase.
Next steps
The potential next stage of research for the team is to perform a randomised controlled trial with the pure compound of ET and other plant-based ingredients, such as L-theanine and catechins from tea leaves, to determine the efficacy of such phytonutrients in delaying cognitive decline. Such interventional studies will lead to more robust conclusion on causal relationship. In addition, Asst Prof Feng and his team also hope to identify other dietary factors that could be associated with healthy brain ageing and reduced risk of age-related conditions in the future.
https://www.sciencedaily.com/releases/2019/03/190312103702.htm