Long-distance skiers may have 'motor reserve' that can delay onset of Parkinson's disease

February 11, 2020

Science Daily IOS Press

To better understand the relationship between physical activity and Parkinson's Disease (PD) investigators in Sweden analyzed medical records of nearly 200,000 long-distance skiers who took part in the Vasaloppet cross-country ski race. They established that a physically active lifestyle is associated with close to a 30% reduced risk for PD, which might be explained by a motor reserve among the physically active, however, this dissipates as individuals age. Their results are published in the Journal of Parkinson's Disease (JPD).

Studies have shown the enormous benefits of exercise in many disorders including neurodegenerative diseases, but the reasons are not always clear. "Exercise seems to protect against the motor symptoms of PD but not necessarily against the brain damage caused by PD," explained co-lead investigator Tomas T. Olsson, MD, Department of Neurology, Skåne University Hospital, and Department of Experimental Medical Science, Experimental Dementia Research Unit, Lund University, Lund, Sweden.

"To understand the mechanisms behind the protective effects of exercise it is very important to establish whether exercise gives people a greater reserve or direct protection," noted co-lead investigator Martina Svensson, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden.

To investigate the degree to which physical activity is associated with long-term lower risk of PD and whether this association can be explained by physically active people being able to sustain more PD neuropathology before the onset of clinical symptoms, investigators analyzed long-term data about the incidence of PD among long-distance skiers. They followed 197,685 participants (median age 36 years; 38% women) in the Vasaloppet, an annual cross-country ski race of up to 90 km, from 1989 to 2010 and compared them to 197,684 age-matched non-skiers. Incidence of PD was taken from the Swedish National Patient Registry

Investigators found that the skiers were almost 30% less likely to develop PD than non-skiers. However, this dissipates with time and increasing age and results in diagnoses of PD among skiers matching the general population.

"We speculate that this would be consistent with the hypothesis that individuals who are physically well-trained have a greater motor reserve, which for every given level of Parkinson's brain damage would result in less motor symptoms thus delaying the diagnosis of PD," noted senior investigator Tomas Deierborg, PhD, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden. "This is analogous to the well-established concept of cognitive reserve in dementia in which the well-educated can sustain more brain pathology without clinical dementia. It highlights the importance of staying physically active throughout life in order to have a reserve to better cope when the frailties and diseases of old age inevitably arrive."

"If a person is physically active, it may be possible to maintain mobility for longer, despite the pathological changes in the brain," added Dr. Olsson.

JPD's Co-Editor-in-Chief Bastiaan R. Bloem, MD, PhD, Director, Radboudumc Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands, commented, "There is an enormous interest in developing new therapies that can help to lower the risk of developing PD. This present study by Olsson and colleagues is particularly exciting in that regard, because it suggests that a readily available intervention -- exercise -- can actually achieve this. The study also provides an explanation why exercise does not offer a complete protection against PD; it supports the motor reserve of the brain, and as such, probably helps to postpone rather than fully prevent the onset of manifest Parkinson symptoms."

PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

https://www.sciencedaily.com/releases/2020/02/200211104915.htm

Sleep deprivation accelerates Alzheimer's brain damage

January 24, 2019

Science Daily/Washington University School of Medicine

A study in mice and people shows that sleep deprivation causes tau levels to rise and tau tangles to spread through the brain. Tau tangles are associated with Alzheimer's disease and brain damage.

Poor sleep has long been linked with Alzheimer's disease, but researchers have understood little about how sleep disruptions drive the disease.

Now, studying mice and people, researchers at Washington University School of Medicine in St. Louis have found that sleep deprivation increases levels of the key Alzheimer's protein tau. And, in follow-up studies in the mice, the research team has shown that sleeplessness accelerates the spread through the brain of toxic clumps of tau - a harbinger of brain damage and decisive step along the path to dementia.

These findings, published online Jan. 24 in the journal Science, indicate that lack of sleep alone helps drive the disease, and suggests that good sleep habits may help preserve brain health.

"The interesting thing about this study is that it suggests that real-life factors such as sleep might affect how fast the disease spreads through the brain," said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "We've known that sleep problems and Alzheimer's are associated in part via a different Alzheimer's protein -- amyloid beta -- but this study shows that sleep disruption causes the damaging protein tau to increase rapidly and to spread over time."

Tau is normally found in the brain -- even in healthy people -- but under certain conditions it can clump together into tangles that injure nearby tissue and presage cognitive decline. Recent research at the School of Medicine has shown that tau is high in older people who sleep poorly. But it wasn't clear whether lack of sleep was directly forcing tau levels upward, or if the two were associated in some other way. To find out, Holtzman and colleagues including first authors Jerrah Holth, PhD, a staff scientist, and Sarah Fritschi, PhD, a former postdoctoral scholar in Holtzman's lab, measured tau levels in mice and people with normal and disrupted sleep.

Mice are nocturnal creatures. The researchers found that tau levels in the fluid surrounding brain cells were about twice as high at night, when the animals were more awake and active, than during the day, when the mice dozed more frequently. Disturbing the mice's rest during the day caused daytime tau levels to double.

Much the same effect was seen in people. Brendan Lucey, MD, an assistant professor of neurology, obtained cerebrospinal fluid -- which bathes the brain and spinal cord -- from eight people after a normal night of sleep and again after they were kept awake all night. A sleepless night caused tau levels to rise by about 50 percent, the researchers discovered.

Staying up all night makes people stressed and cranky and likely to sleep in the next chance they get. While it's hard to judge the moods of mice, they, too, rebounded from a sleepless day by sleeping more later. To rule out the possibility that stress or behavioral changes accounted for the changes in tau levels, Fritschi created genetically modified mice that could be kept awake for hours at a time by injecting them with a harmless compound. When the compound wears off, the mice return to their normal sleep-wake cycle -- without any signs of stress or apparent desire for extra sleep.

Using these mice, the researchers found that staying awake for prolonged periods causes tau levels to rise. Altogether, the findings suggest that tau is routinely released during waking hours by the normal business of thinking and doing, and then this release is decreased during sleep allowing tau to be cleared away. Sleep deprivation interrupts this cycle, allowing tau to build up and making it more likely that the protein will start accumulating into harmful tangles.

In people with Alzheimer's disease, tau tangles tend to emerge in parts of the brain important for memory -- the hippocampus and entorhinal cortex -- and then spread to other brain regions. As tau tangles mushroom and more areas become affected, people increasingly struggle to think clearly.

To study whether the spread of tau tangles is affected by sleep, the researchers seeded the hippocampi of mice with tiny clumps of tau and then kept the animals awake for long periods each day. A separate group of mice also was injected with tau tangles but was allowed to sleep whenever they liked. After four weeks, tau tangles had spread further in the sleep-deprived mice than their rested counterparts. Notably, the new tangles appeared in the same areas of the brain affected in people with Alzheimer's.

"Getting a good night's sleep is something we should all try to do," Holtzman said. "Our brains need time to recover from the stresses of the day. We don't know yet whether getting adequate sleep as people age will protect against Alzheimer's disease. But it can't hurt, and this and other data suggest that it may even help delay and slow down the disease process if it has begun."

The researchers also found that disrupted sleep increased release of synuclein protein, a hallmark of Parkinson's disease. People with Parkinson's -- like those with Alzheimer's -- often have sleep problems.

https://www.sciencedaily.com/releases/2019/01/190124141536.htm