mild cognitive impairment

Amyloid is a less accurate marker for measuring severity, progression of Alzheimer's

August 6, 2019

Science Daily/University of Pennsylvania School of Medicine

Researchers find fluorodeoxyglucose (FDG) PET is a better indicator of cognitive performance when compared to PET scans that detect amyloid protein.

 

While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimer's disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brain's glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimer's and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain. This suggests that FDG-PET is also a better means for determining the effectiveness of Alzheimer's therapies, as well as tracking patients' disease advancement, in both clinical and research settings. Results of this study are detailed in the August issue of the Journal of Alzheimer's Disease.

 

"Both florbetapir-PET and FDG-PET are approved diagnostic methods for Alzheimer's disease, and both appear to be effective in indicating some sort of cognitive impairment. However, we have now shown that FDG-PET is significantly more precise in clinical studies, and it is also available for routine use with modest costs," said the study's co-principal investigator Abass Alavi, MD, PhD, a professor of Radiology at Penn. "Our results support the notion that amyloid imaging does not reflect levels of brain function, and therefore it may be of limited value for assessing patients with cognitive decline."

 

Alzheimer's disease, the most common cause of dementia, is the sixth leading cause of death in the United States, affecting up to 5.8 million Americans currently. As clinicians aim to spot and treat the symptoms of dementia in its earliest stages, PET plays an increasingly pivotal role in diagnosing and monitoring Alzheimer's disease, as well as MCI, a condition that often precedes dementia.

 

Two of the most significant biomarkers found in Alzheimer's are decreased glucose uptake and the accumulation of amyloid plaques in the brain. PET scans use different radioactive drugs, called radiotracers, to measure these biomarkers within the brain tissue of patients with cognitive impairment. FDG-PET is one of the most commonly used imaging techniques to diagnose Alzheimer's. However, in recent years, several other radiotracers, such as florbetapir, have been developed to detect the deposition of amyloid plaques.

 

Recently, the effectiveness of amyloid imaging as a strategy for monitoring dementia symptoms has been called into question. While the presence of amyloid plaques in the brain is considered as being characteristic of Alzheimer's, some studies have shown that large amounts of amyloid plaques were present in healthy, non-demented individuals. Conversely, recent clinical trials have shown that the intended removal of amyloid from the brains of patients with Alzheimer's disease led to no change in, or even worsened, cognitive performance.

 

In this study, the researchers evaluated 63 individuals, including 19 with clinically diagnosed Alzheimer's disease, 23 with MCI, and 21 healthy individuals. The study participants underwent both FDG- and florbetapir-PET imaging. They were then assessed with a Mini Mental Status Examination (MMSE), a widely used diagnostic test for detecting and assessing the severity of cognitive impairment. The researchers used a novel "global quantification approach" to generate data from five different regions of the brain, which were correlated with the results from the MMSE scores.

 

The study revealed that both FDG- and florbetapir-PET scans are able to effectively discriminate the individuals with dementia from the healthy control group. However, when compared with the MMSE scores, the correlation between low cognitive performance and high levels of amyloid was significantly weaker than the correlation between FDG and low cognitive performance for all groups included in the study. This suggests that FDG-PET is a more sensitive indicator of cognitive decline.

 

"Amyloid imaging has a value in diagnosing or ruling out Alzheimer's disease, but it's a bit like all or nothing. Our study shows that it can reveal disease, but you wouldn't be able to differentiate between someone who had very mild or very severe symptoms," said co-principal investigator Andrew Newberg, MD, a professor of Radiology at Thomas Jefferson University, who added that these findings have important implications for clinical research.

 

"In a clinical drug trial, for example, it may be more relevant to do an FDG-PET scan, rather than using amyloid as a marker, to find out whether the therapy is working," Newberg said.

 

While FDG-PET may not be a perfect diagnostic tool, the study confirms that currently it is the best available method for monitoring symptoms of dementia, according to Alavi.

 

"Right now, FDG is king when it comes to looking at brain function, not only in Alzheimer's disease, but also diseases like vascular dementia and cancer," Alavi said.

https://www.sciencedaily.com/releases/2019/08/190806121133.htm

Pink noise boosts deep sleep in mild cognitive impairment patients

Sound stimulation in deep sleep improved recall for some in small pilot study

June 28, 2019

Science Daily/Northwestern University

Gentle sound stimulation played during deep sleep enhanced deep sleep for people with mild cognitive impairment, who are at risk for Alzheimer's disease, a new study found. Those whose brains responded the most robustly to the sound stimulation showed an improved memory response the following day. These results suggest improving sleep is a promising novel approach to stave off dementia. The technology can be adapted for home use.

 

Gentle sound stimulation played during specific times during deep sleep enhanced deep or slow-wave sleep for people with mild cognitive impairment, who are at risk for Alzheimer's disease.

 

The individuals whose brains responded the most robustly to the sound stimulation showed an improved memory response the following day.

 

"Our findings suggest slow-wave or deep sleep is a viable and potentially important therapeutic target in people with mild cognitive impairment," said Dr. Roneil Malkani, assistant professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine sleep medicine physician. "The results deepen our understanding of the importance of sleep in memory, even when there is memory loss."

 

Deep sleep is critical for memory consolidation. Several sleep disturbances have been observed in people with mild cognitive impairment. The most pronounced changes include reduced amount of time spent in the deepest stage of sleep.

 

"There is a great need to identify new targets for treatment of mild cognitive impairment and Alzheimer's disease," Malkani added. Northwestern scientists had previously shown that sound stimulation improved memory in older adults in a 2017 study.

 

Because the new study was small -- nine participants -- and some individuals responded more robustly than others, the improvement in memory was not considered statistically significant. However, there was a significant relationship between the enhancement of deep sleep by sound and memory: the greater the deep sleep enhancement, the better the memory response.

 

"These results suggest that improving sleep is a promising novel approach to stave off dementia," Malkani said.

 

The paper will be published June 28 in the Annals of Clinical and Translational Neurology.

 

For the study, Northwestern scientists conducted a trial of sound stimulation overnight in people with mild cognitive impairment. Participants spent one night in the sleep laboratory and another night there about one week later. Each participant received sounds on one of the nights and no sounds on the other. The order of which night had sounds or no sounds was randomly assigned. Participants did memory testing the night before and again in the morning. Scientists then compared the difference in slow-wave sleep with sound stimulation and without sounds, and the change in memory across both nights for each participant.

 

The participants were tested on their recall of 44 word pairs. The individuals who had 20% or more increase in their slow wave activity after the sound stimulation recalled about two more words in the memory test the next morning. One person with a 40% increase in slow wave activity remembered nine more words.

 

The sound stimulation consisted of short pulses of pink noise, similar to white noise but deeper, during the slow waves. The system monitored the participant's brain activity. When the person was asleep and slow brain waves were seen, the system delivered the sounds. If the patient woke up, the sounds stopped playing.

 

"As a potential treatment, this would be something people could do every night," Malkani said.

 

The next step, when funding is available, is to evaluate pink noise stimulation in a larger sample of people with mild cognitive impairment over multiple nights to confirm memory enhancement and see how long the effect lasts, Malkani said.

https://www.sciencedaily.com/releases/2019/06/190628120531.htm

Exercise may improve memory in heart failure patients

May 4, 2019

Science Daily/European Society of Cardiology

Two-thirds of patients with heart failure have cognitive problems, according to research presented today at EuroHeartCare 2019, a scientific congress of the European Society of Cardiology (ESC).1

 

Heart failure patients who walked further in a six-minute test, which shows better fitness, as well as those who were younger and more highly educated, were significantly less likely to have cognitive impairment. The results suggest that fitter patients have healthier brain function.

 

Study author Professor Ercole Vellone, of the University of Rome "Tor Vergata," Italy, said: "The message for patients with heart failure is to exercise. We don't have direct evidence yet that physical activity improves cognition in heart failure patients, but we know it improves their quality and length of life. In addition, studies in older adults have shown that exercise is associated with improved cognition -- we hope to show the same for heart failure patients in future studies."

 

The cognitive abilities that are particularly damaged in heart failure patients are memory, processing speed (time it takes to understand and react to information), and executive functions (paying attention, planning, setting goals, making decisions, starting tasks).

 

"These areas are important for memorising healthcare information and having the correct understanding and response to the disease process," said Professor Vellone. "For example, heart failure patients with mild cognitive impairment may forget to take medicines and may not comprehend that weight gain is an alarming situation that requires prompt intervention."

 

The study highlights that cognitive dysfunction is a common problem in patients with heart failure -- 67% had at least mild impairment. "Clinicians might need to adapt their educational approach with heart failure patients -- for example involving a family caregiver to oversee patient adherence to the prescribed treatment," said Professor Vellone.

 

The study used data from the HF-Wii study, which enrolled 605 patients with heart failure from six countries. The average age was 67 and 71% were male. The Montreal Cognitive Assessment test was used to measure cognitive function and exercise capacity was measured with the six-minute walk test.

 

Professor Vellone said: "There is a misconception that patients with heart failure should not exercise. That is clearly not the case. Find an activity you enjoy that you can do regularly. It could be walking, swimming, or any number of activities. There is good evidence that it will improve your health and your memory, and make you feel better."

https://www.sciencedaily.com/releases/2019/05/190504130301.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

Exercise may be the best medicine for Alzheimer's disease

July 30, 2013

Science Daily/University of Maryland

Regular, moderate exercise could improve memory and cognitive function in those at risk for Alzheimer's disease in a way no drug can. Scientists studied the effects of exercise on a group of older adults with mild cognitive impairment and found that brain activity associated with memory, measured by neuroimaging, improved after 12 weeks of a moderate exercise program.

 

New research out of the University of Maryland School of Public Health shows that exercise may improve cognitive function in those at risk for Alzheimer's by improving the efficiency of brain activity associated with memory. Memory loss leading to Alzheimer's disease is one of the greatest fears among older Americans. While some memory loss is normal and to be expected as we age, a diagnosis of mild cognitive impairment, or MCI, signals more substantial memory loss and a greater risk for Alzheimer's, for which there currently is no cure.

 

The study, led by Dr. J. Carson Smith, assistant professor in the Department of Kinesiology, provides new hope for those diagnosed with MCI. It is the first to show that an exercise intervention with older adults with mild cognitive impairment (average age 78) improved not only memory recall, but also brain function, as measured by functional neuroimaging (via fMRI). The findings are published in the Journal of Alzheimer's Disease.

 

"We found that after 12 weeks of being on a moderate exercise program, study participants improved their neural efficiency -- basically they were using fewer neural resources to perform the same memory task," says Dr. Smith. "No study has shown that a drug can do what we showed is possible with exercise."

 

Recommended Daily Activity: Good for the Body, Good for the Brain

 

Two groups of physically inactive older adults (ranging from 60-88 years old) were put on a 12-week exercise program that focused on regular treadmill walking and was guided by a personal trainer. Both groups -- one which included adults with MCI and the other with healthy brain function -- improved their cardiovascular fitness by about ten percent at the end of the intervention. More notably, both groups also improved their memory performance and showed enhanced neural efficiency while engaged in memory retrieval tasks.

 

The good news is that these results were achieved with a dose of exercise consistent with the physical activity recommendations for older adults. These guidelines urge moderate intensity exercise (activity that increases your heart rate and makes you sweat, but isn't so strenuous that you can't hold a conversation while doing it) on most days for a weekly total of 150 minutes.

 

Measuring Exercise's Impact on Brain Health and Memory

 

One of the first observable symptoms of Alzheimer's disease is the inability to remember familiar names. Smith and colleagues had study participants identify famous names and measured their brain activation while engaged in correctly recognizing a name -- e.g., Frank Sinatra, or other celebrities well known to adults born in the 1930s and 40s. "The task gives us the ability to see what is going on in the brain when there is a correct memory performance," Smith explains.

 

Tests and imaging were performed both before and after the 12-week exercise intervention. Brain scans taken after the exercise intervention showed a significant decrease in the intensity of brain activation in eleven brain regions while participants correctly identified famous names. The brain regions with improved efficiency corresponded to those involved in the pathology of Alzheimer's disease, including the precuneus region, the temporal lobe, and the parahippocampal gyrus.

 

The exercise intervention was also effective in improving word recall via a "list learning task," i.e., when people were read a list of 15 words and asked to remember and repeat as many words as possible on five consecutive attempts, and again after a distraction of being given another list of words.

 

"People with MCI are on a very sharp decline in their memory function, so being able to improve their recall is a very big step in the right direction," Smith states.

 

The results of Smith's study suggest that exercise may reduce the need for over-activation of the brain to correctly remember something. That is encouraging news for those who are looking for something they can do to help preserve brain function.

 

Dr. Smith has plans for a larger study that would include more participants, including those who are healthy but have a genetic risk for Alzheimer's, and follow them for a longer time period with exercise in comparison to other types of treatments. He and his team hope to learn more about the impact of exercise on brain function and whether it could delay the onset or progression of Alzheimer's disease.

http://www.sciencedaily.com/releases/2013/07/130730123249.htm

 

Memory May Decline Rapidly Even in Stage Before Alzheimer's Disease

March 23, 2010

Science Daily/American Academy of Neurology

Memory and thinking skills may decline rapidly for people who have mild cognitive impairment, which is the stage before Alzheimer's disease when people have mild memory problems but no dementia symptoms, and even more rapidly when dementia begins, which is when Alzheimer's disease is usually diagnosed.

 

"These results show that we need to pay attention to this time before Alzheimer's disease is diagnosed, when people are just starting to have problems forgetting things," said study author Robert S. Wilson, PhD, of Rush University Medical Center in Chicago.

 

"The changes in rate of decline occur as the brain atrophies due to the disease, first mainly in the hippocampus during the initial symptomatic stage, referred to as mild cognitive impairment, then in the temporal, parietal and frontal cortex during the dementing illness phase of Alzheimer's disease," said David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., and Fellow of the American Academy of Neurology, who wrote an editorial accompanying the article.

http://www.sciencedaily.com/releases/2010/03/100322171008.htm

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