Early Alzheimer's detection up to 17 years in advance

July 21, 2022

Science Daily/Ruhr-University Bochum

A sensor identifies misfolded protein biomarkers in the blood. This offers a chance to detect Alzheimer's disease before any symptoms occur. Researchers intend to bring it to market maturity.

Alzheimer's disease has a symptom-free period of 15 to 20 years before the first clinical symptoms emerge. Using an immuno-infrared sensor developed in Bochum, a research team is able to identify signs of Alzheimer's disease in the blood up to 17 years before the first clinical symptoms appear. The sensor detects the misfolding of the protein biomarker amyloid-beta. As the disease progresses, this misfolding causes characteristic deposits in the brain, so-called plaques.

"Our goal is to determine the risk of developing Alzheimer's dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time," says Professor Klaus Gerwert, founding director of the Centre for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum. His team cooperated for the study with a group at the German Cancer Research Centre in Heidelberg (DKFZ) headed by Professor Hermann Brenner.

The team published the results obtained with the immuno-infrared sensor in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association on 19 July 2022. This study is supported by a comparative study published in the same journal on 2 March 2022, in which the researchers used complementary single-molecule array (SIMOA) technology.

Early detection of symptom-free people with a high risk of Alzheimer's disease

The researchers analysed blood plasma from participants in the ESTHER study conducted in Saarland for potential Alzheimer's biomarkers. The blood samples had been taken between 2000 and 2002 and then frozen. At that time, the test participants were between 50 and 75 years old and hadn't yet been diagnosed with Alzheimer's disease. For the current study, 68 participants were selected who had been diagnosed with Alzheimer's disease during the 17-year follow-up and compared with 240 control subjects without such a diagnosis. The team headed by Klaus Gerwert and Hermann Brenner aimed to find out whether signs of Alzheimer's disease could already be found in the blood samples at the beginning of the study.

The immuno-infrared sensor was able to identify the 68 test subjects who later developed Alzheimer's disease with a high degree of test accuracy. For comparison, the researchers examined other biomarkers with the complementary, highly sensitive SIMOA technology -- specifically the P-tau181 biomarker, which is currently being proposed as a promising biomarker candidate in various studies. "Unlike in the clinical phase, however, this marker is not suitable for the early symptom-free phase of Alzheimer's disease," as Klaus Gerwert summarises the results of the comparative study. "Surprisingly, we found that the concentration of glial fibre protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor." Still, by combining amyloid-beta misfolding and GFAP concentration, the researchers were able to further increase the accuracy of the test in the symptom-free stage.

Start-up aims to bring immuno-infrared sensor to market maturity

The Bochum researchers hope that an early diagnosis based on the amyloid-beta misfolding could help to apply Alzheimer's drugs at such an early stage that they have a significantly better effect -- for example, the drug Aduhelm, which was recently approved in the USA. "We plan to use the misfolding test to establish a screening method for older people and determine their risk of developing Alzheimer's dementia," says Klaus Gerwert. "The vision of our newly founded start-up betaSENSE is that the disease can be stopped in a symptom-free stage before irreversible damage occurs." Even though the sensor is still in the development phase, the invention has already been patented worldwide. BetaSENSE aims to bring the immuno-infrared sensor to market and have it approved as a diagnostic device so that it can be used in clinical labs.

Clinical trials with Alzheimer's drugs often fail

Approved by the FDA in the USA in spring 2021, the drug Aduhelm has been shown to clear amyloid-beta plaques from the brain. However, previous studies showed it had only a minor effect on clinical symptoms such as memory loss and disorientation. Consequently, the European Medicines Agency decided in winter 2021 not to approve the drug in Europe. "Up to now, clinical trials for Alzheimer's drugs have been failing by the dozen, apparently because the established plaque tests used in the trials don't flag up the disease in time," says Gerwert. "It seems that once plaques are deposited, they induce irreversible damage in the brain." In the tests used to date, the plaques are either detected directly in the brain with the complex and expensive PET scan technology or indirectly determined in a less complex way using protein biomarker concentrations in invasively obtained cerebrospinal fluid with ELISA or mass spectrometry technology. In contrast to established plaque diagnostics, the immuno-infrared sensor indicates the earlier misfolding of amyloid-beta, which causes the later plaque deposition. "However, it is still controversially discussed whether this misfolding is the cause of Alzheimer's disease or if it's just an accompanying factor," points out Gerwert. "For the therapeutic approach, this question is crucial, but it is irrelevant for the diagnosis. The misfolding indicates the onset of Alzheimer's disease."

"The exact timing of therapeutic intervention will become even more important in the future," predicts Léon Beyer, first author and PhD student in Klaus Gerwert's team. "The success of future drug trials will depend on the study participants being correctly characterised and not yet showing irreversible damage at study entry."

Biomarkers for Parkinson's and ALS

Misfolded proteins play a central role in many neurodegenerative diseases, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). As the researchers have showed, the immuno-infrared sensor can in principle also be used to detect other misfolded proteins, such as TDP-43, which is characteristic of ALS. They don't measure the concentration of a specific protein, but detect its misfolding using disease-specific antibodies. "Most importantly, this platform technology enables us to make a differential, precise biomarker-based diagnosis in the early stages of neurodegenerative diseases, in which the currently applied symptom-based diagnosis is very difficult and prone to errors," stresses Gerwert.

https://www.sciencedaily.com/releases/2022/07/220721132038.htm

Do benefits of physical, mental activity on thinking differ for men and women?

July 20, 2022

Science Daily/American Academy of Neurology

Studies have shown that physical and mental activity help preserve thinking skills and delay dementia. A new study suggests that these benefits may vary for men and women. The study is published in the July 20, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study looked at the effects of physical and mental activities, such as reading, going to classes, or playing cards or games, on cognitive reserve in the areas of thinking speed and memory. Cognitive reserve is the buffer that occurs when people have strong thinking skills even when their brains show signs of the underlying changes associated with cognitive impairment and dementia.

"We found that greater physical activity was associated with greater thinking speed reserve in women, but not in men," said study author Judy Pa, PhD, of the University of California, San Diego. "Taking part in more mental activities was associated with greater thinking speed reserve for both men and women."

Greater physical activity was not associated with memory reserve in men or women.

The study involved 758 people with an average age of 76. Some had no thinking or memory problems, some had mild cognitive impairment, and some had dementia. The participants had brain scans and took thinking speed and memory tests. To calculate cognitive reserve, people's thinking tests scores were compared against the changes in the brain associated with dementia, such as the total volume of the hippocampus, a key brain region impacted by Alzheimer's disease.

People were also asked about their usual weekly physical activity. For mental activity, they were asked whether they participated in three types of activities in the past 13 months: reading magazines, newspapers or books; going to classes; and playing cards, games or bingo. They were given one point for each type of activity, for a maximum of three points.

For mental activity, participants averaged 1.4 points. For physical activity, participants took part in an average of at least 15 minutes per week of activities that elevate heart rates such as brisk walking and biking.

Pa said that each additional mental activity people participated in corresponded to 13 fewer years of aging in their processing speed in their thinking skills -- 17 years among men and 10 years among women.

"As we have arguably few-to-no effective treatments for Alzheimer's disease, prevention is crucial. An ounce of prevention is worth a pound of treatment," Pa said. "To know that people could potentially improve their cognitive reserve by taking simple steps such as going to classes at the community center, playing bingo with their friends or spending more time walking or gardening is very exciting."

Pa said that based on the effect sizes seen in the study, a doubling of the amount of physical activity would be equivalent to an estimated 2.75 fewer years of aging when it comes to women's processing speed in their thinking skills.

Researchers also looked at whether the relationship between physical and mental activities and cognitive reserve was affected by the gene that carries the strongest risk for Alzheimer's, called APOE e4. They found that for women, having the gene lessens the effects of the beneficial relationship between physical and mental activities and cognitive reserve.

The study does not prove that physical and mental activities help improve cognitive reserve. It only shows an association.

A limitation of the study was that people reported their own physical and mental activity, so they may not have remembered correctly. Also, structural and societal factors that affect cognitive reserve, such as education, were not measured in the study.

The study was supported by the National Institute on Aging and the National Center for Advancing Translational Sciences.

https://www.sciencedaily.com/releases/2022/07/220720193720.htm

Tracking daily movement patterns may one day help predict dementia

Study explores possibility that changes in daily activity patterns may predict Alzheimer's and other cognitive decline in older adults

July 19, 2022

Science Daily/Johns Hopkins University Bloomberg School of Public Health

Researchers found significant differences in movement patterns between participants with normal cognition and those with mild cognitive impairment or Alzheimer's disease.

Wearable movement-tracking devices may someday be useful in providing early warnings of cognitive decline among older adults, suggest new findings from researchers at the Johns Hopkins Bloomberg School of Public Health.

The researchers analyzed data from ActiGraph activity monitors, which use an activity-tracking sensor similar to those found in Fitbits and Apple watches, worn by nearly 600 participants in a long-running community-based health study of older adults. They found significant differences in movement patterns between participants with normal cognition and those with mild cognitive impairment or Alzheimer's disease. These differences included less activity during waking hours and more fragmented activity during afternoons among the mild cognitive impairment/Alzheimer's participants.

The results were published July 19 in the Journal of Alzheimer's Disease.

"We tend to think of physical activity as a potential therapy to slow cognitive decline, but this study reminds us that cognitive decline may in turn slow physical activity -- and we might someday be able to monitor and detect such changes for earlier and more efficient testing to delay and maybe prevent cognitive impairment that leads to Alzheimer's," says study lead author Amal Wanigatunga, PhD, MPH, assistant scientist in the Department of Epidemiology at the Bloomberg School.

The recent introduction of wearable activity-tracking devices, which are now used by tens of millions of people around the world, has presented an important opportunity for health researchers to measure and track changes in physical movement. The devices can provide automatic, objective measures of daytime physical activity, sleep patterns, heart rate, and blood oxygen levels -- and they are typically Internet-connected, allowing their manufacturers to build datasets covering millions of users. Researchers previously did not have such an easy way to access such health-relevant data at such a large scale.

The aim of the new study was to determine if activity-tracker patterns recorded from a cohort of older adults differ meaningfully between the cognitively normal and the cognitively impaired. Alzheimer's disease, the most common form of dementia, is known to be a decades-long process, and researchers generally expect that future disease-modifying interventions will be more effective when started earlier in the disease course. If scientists could identify a distinctive change in activity that predicts the slide into mild cognitive impairment and, eventually, Alzheimer's and other forms of dementia, then in principle older individuals who show this change in activity could be given further cognitive testing -- and, when available, earlier treatment.

The study made use of data from a larger, ongoing health research project known as the Baltimore Longitudinal Study of Aging (BLSA), in which the National Institute on Aging has been studying thousands of people in the Baltimore area since 1958. The analysis was based on 585 BLSA participants for whom sufficient activity-tracker data and cognitive assessments were available during the period July 2015-December 2019. These included 36 participants with either mild cognitive impairment or Alzheimer's diagnoses.

Adjusting for differences based on age, sex, and race, the researchers found that overall differences in all-day activity measures were not strongly different between the mild cognitive impairment/Alzheimer's and normal cognition groups. However, when the researchers focused on activity patterns during certain times of the day, some differences were revealed.

In the mornings (6 a.m. to noon) and even more so in the afternoons (noon to 6 p.m.), the mild cognitive impairment/Alzheimer's group had significantly lower measures of activity compared to the normal group. The most striking finding was that activity "fragmentation" -- a breaking-up of activity into smaller time periods -- was 3.4 percent higher for the mild cognitive impairment/Alzheimer's participants during the afternoon period.

"Seeing this difference in the afternoons was interesting -- one of the main symptoms of Alzheimer's dementia is the 'sundowning' phenomenon involving increased confusion and mood changes that start in the afternoon, and it might be that these activity markers are capturing some movement related to these symptoms," Wanigatunga says.

The findings, he notes, are preliminary because of the cross-sectional, "snapshot" nature of the study design, though they do support the idea that cognitive decline into mild cognitive impairment and dementia is accompanied by changes in activity patterns.

He and his colleagues plan additional studies that will follow participants over time, to see if measurable yet slight changes in everyday activity patterns help capture early symptomology of mild cognitive impairment and subsequent Alzheimer's disease dementia. 

https://www.sciencedaily.com/releases/2022/07/220719162105.htm

Research reveals how brain inflammation may link Alzheimer's risk, sleep disturbance

July 13, 2022

Science Daily/University of California – Irvine

A multisite research team from the University of California, Irvine, the University of Wisconsin-Madison and Wake Forest University has discovered that brain inflammation may link Alzheimer's disease risk with sleep disturbance, which may aid early detection and prevention efforts by identifying novel treatment targets at preclinical stages.

Brain inflammation, sleep disturbance and disrupted brain waves have all been associated with Alzheimer's disease, but the interactions among them have not been investigated until now. The study, published online today in the journal Sleep, examined whether inflammation had any effect on specific brain waves called fast sleep spindles, which have been shown to promote long-term memory retention.

"Our findings indicate that age-related increases in brain inflammation have a downstream effect on Alzheimer's disease-related tau proteins and neuronal synaptic integrity. This results in deficits in the brain's capacity to generate fast sleep spindles, which contribute to age-related memory impairment in older adults. Discovering these mechanisms is an important step in identifying at-risk individuals as early as possible and developing targeted interventions," said Bryce Mander, Ph.D., UCI assistant professor of psychiatry & human behavior and the study's lead and co-corresponding author.

Chronic activation of the brain's immune cells, called "glial cells," increases with age, elevating production of beta-amyloid and tau proteins, the hallmarks of Alzheimer's disease. Independently, sleep disturbance has been linked to Alzheimer's disease pathology in the brain, and studies have also indicated an association between sleep disturbance and inflammation. Selectively disrupted fast sleep spindles have been identified in normal aging as well as preclinical stages of Alzheimer's disease, but it has not been clear what causes this and what it means for memory impairment in older at-risk adults.

For the study, 58 cognitively unimpaired adults in their 50s and 60s were examined at the University of Wisconsin-Madison. All had a parental history of Alzheimer's or a genetic risk factor for it, but none of them had beta-amyloid plaques or neurofibrillary tau tangles. Sleep was recorded overnight using high-density electroencephalography to map brain wave expression during sleep, and overnight memory retention was assessed. Participants also underwent a lumbar puncture so that cerebrospinal fluid biomarkers of central nervous system inflammation, beta-amyloid and tau proteins, and neuronal integrity could be examined.

Statistical tests were used to evaluate whether the effect of age on fast sleep spindles was mediated by Alzheimer's-related proteins. Researchers found that activation of two types of glial cells -- microglia and astrocytes, which trigger brain inflammation -- was associated with disrupted expression of fast sleep spindles. The fact that these relationships were identified in people without any accumulation of beta-amyloid plaques or neurofibrillary tangles indicates that sleep deficits and inflammation might be among the earliest warning signs of Alzheimer's disease.

"We don't yet know whether anyone in this study will develop Alzheimer's disease dementia, but one of the reasons that our studies enroll participants in midlife is so that we can potentially detect problems before people develop disease symptoms," said co-author Barbara Bendlin, Ph.D., professor of medicine at the University of Wisconsin-Madison.

"These findings show that the effects of brain inflammation on sleep spindles and memory occur through its effects on neuronal activity and Alzheimer's disease-related proteins and are apparent even before pathological positivity," said Dr. Ruth Benca, the study's senior and co-corresponding author and Wake Forest professor and chair of psychiatry and behavioral medicine. "This offers a promising therapeutic target to stop cognitive decline associated with aging and Alzheimer's."

https://www.sciencedaily.com/releases/2022/07/220713143933.htm

Whether you're 18 or 80, lifestyle may be more important than age in determining dementia risk

July 13, 2022

Science Daily/Baycrest Centre for Geriatric Care

Individuals with no dementia risk factors, such as smoking, diabetes or hearing loss, have similar brain health as people who are 10 to 20 years younger than them, according to a new Baycrest study. The study found that a single dementia risk factor could reduce cognition by the equivalent of up to three years of aging.

"Our results suggest lifestyle factors may be more important than age in determining someone's level of cognitive functioning. This is great news, since there's a lot you can do to modify these factors, such as managing diabetes, addressing hearing loss, and getting the support you need to quit smoking," says Dr. Annalise LaPlume, Postdoctoral Fellow at Baycrest's Rotman Research Institute (RRI) and the study's lead author.

The study is one of the first to look at lifestyle risk factors for dementia across the entire lifespan.

"While most studies of this nature look at mid- and older-adulthood, we also included data from participants as young as 18, and we found that risk factors had a negative impact on cognitive performance across all ages. This is crucial as it means risk factors can and should be addressed as early as possible," says Dr. Nicole Anderson, Senior Scientist at the RRI, Associate Scientific Director of Baycrest's Kimel Family Centre for Brain Health and Wellness, and senior author of this study.

The study, published today in the journal Alzheimer's & Dementia: Diagnosis, Assessment, and Disease Monitoring, a journal of the Alzheimer's Association, included data from 22,117 people aged 18 to 89 who completed the Cogniciti Brain Health Assessment, developed by Baycrest. Participants took the test in their own homes by going to the Cogniciti website (https://cogniciti.com/). The test takes around 20 minutes to complete and consists of a background questionnaire and four cognitive tasks.

The researchers looked at participants' performance on memory and attention tests, and how this was impacted by eight modifiable risk factors for dementia: low education (less than a high school diploma), hearing loss, traumatic brain injury, alcohol or substance abuse, hypertension, smoking (currently or in the past four years), diabetes and depression.

Each factor led to a decrease in cognitive performance by as much as three years of aging, with each additional factor contributing the same amount of decline. For example, having three risk factors could lead to a decrease in cognitive performance equivalent to as much as nine years of aging. The effects of the risk factors increased with age, as did the number of risk factors people had.

"All in all, our research shows that you have the power to decrease your risk of cognitive decline and dementia," says Dr. LaPlume. "Start addressing any risk factors you have now, whether you're 18 or 90, and you'll support your brain health to help yourself age fearlessly."

This research was supported by the Alzheimer Society of Canada, and the Natural Sciences and Engineering Research Council of Canada.

With additional funding, the researchers could look further into the differences between normal agers and "super agers" -- people who have identical cognitive performance to those several decades younger than them.

https://www.sciencedaily.com/releases/2022/07/220713114643.htm

Predicting the future: A quick, easy scan can reveal late-life dementia risk

June 28, 2022

Science Daily/Edith Cowan University

Researchers have discovered an important link between vascular health and late-life dementia, discovering the calcification of plaques within the abdominal aorta to be a reliable marker for late-life dementia.

Late-life dementia is becoming increasingly common in people after 80 years of age.

A new long-term study has shown a simple and common scan can reveal if people are at increased risk of developing the condition late in life.

Late-life dementia develops when brain cells are damaged from several diseases, some of which cause narrowing of the blood vessels to the brain.

Edith Cowan University (ECU) researchers have discovered an important link between vascular health and late-life dementia.

This link is calcification of the plaques which can build up within the abdominal aorta, which is the largest artery in the body and supplies oxygenated blood from the heart to the abdominal organs and lower limbs.

This calcium build up -- known as 'abdominal aortic calcification', or AAC -- can be very useful to predict cardiovascular disease risk such as heart attack and stroke.

But researchers have now found it is also a reliable marker for late-life dementia.

Led by ECU's Nutrition and Health Innovation Institute and Centre for Precision Health, the international team included researchers from the University of Western Australia, University of Minnesota, Sir Charles Gairdner Hospital and the Marcus Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School.

They examined the AAC results in 968 women from the late 1990s, and then followed their health status for over 15 years.

They found one in two older women had medium to high levels of AAC, and these women were twice as likely to be hospitalized or die from a late-life dementia -- independent of other cardiovascular factors or genetic factors.

Centre for Precision Health director Professor Simon Laws said AAC could identify dementia risk earlier in people's life, which could prove vital in warding off the condition.

"There's an adage in dementia research that what's good for your heart is good for your brain," he said.

"This study reaffirms this link and further adds to our understanding of late-onset dementia risk and potential preventative strategies.

"What's come to light is the importance of modifying risk factors such as diet and physical activity in preventing dementia: you need to intervene early and hopefully this study allows for the earliest possible change and the greatest impact.

"AAC is important as it was able to identify dementia risk in people who don't have the major genetic risk factor present in 50 per cent of people who develop Alzheimer's disease, which is the most common form of dementia."?

A simple test

Conveniently, AAC can be easily detected using lateral spine scans from bone density machines.

These machines are common, with some 600,000 bone density tests performed each year in Australia to screen for osteoporosis.

ECU Associate Professor and National Heart Foundation Future Leader Fellow Joshua Lewis said an additional scan capturing lateral spine images can be performed when people undergo standard bone density tests.

"It's generally very quick and easy to capture these scans and they are less-invasive, cheaper and miniscule in radiation exposure compared to X-rays or CT scans," Professor Lewis said.

"We know the causes of AAC go beyond traditional cardiovascular risk factors and many of these causes overlap with late-life dementia risk factors.

"At ECU we're also working with the computer science team automating the AAC assessments, which will make the process a lot quicker and easier rather than needing a trained imaging expert to read the scans.

"It means these scans may be a cheap, rapid and safe way to screen a large number of susceptible older Australians for higher late-life dementia risk."

Professor Lewis said incorporating dementia risk into discussions surrounding cardiovascular health could see people make necessary lifestyle changes.

"I think the next step is telling people about their AAC and late-life dementia risk to see if this can motivate healthy diet and lifestyle behaviour changes."

Heart Foundation chief medical adviser, Professor Garry Jennings AO, welcomed the research.

"Vascular dementia is an increasingly common disability in older people," Professor Jennings said.

"It is often associated with heart disease or risk factors such as hypertension earlier in life.

"Josh's study is an excellent example of benefits arising from the Heart Foundation's Future Leadership funding program."

'Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: a prospective cohort study' was published in The Lancet Regional Health -- Western Pacific.

https://www.sciencedaily.com/releases/2022/06/220626200205.htm

Flu vaccination linked to 40% reduced risk of Alzheimer's disease

June 24, 2022

Science Daily/University of Texas Health Science Center at Houston

People who received at least one influenza vaccine were 40% less likely than their non-vaccinated peers to develop Alzheimer's disease over the course of four years, according to a new study from UTHealth Houston.

Research led by first author Avram S. Bukhbinder, MD, a recent alumnus of McGovern Medical School at UTHealth Houston, and senior author Paul. E. Schulz, MD, the Rick McCord Professor in Neurology at McGovern Medical School, compared the risk of Alzheimer's disease incidence between patients with and without prior flu vaccination in a large nationwide sample of U.S. adults aged 65 and older.

An early online version of the paper detailing the findings is available in advance of its publication in the Aug. 2 issue of the Journal of Alzheimer's Disease.

"We found that flu vaccination in older adults reduces the risk of developing Alzheimer's disease for several years. The strength of this protective effect increased with the number of years that a person received an annual flu vaccine -- in other words, the rate of developing Alzheimer's was lowest among those who consistently received the flu vaccine every year," said Bukhbinder, who is still part of Schulz's research team while in his first year of residency with the Division of Child Neurology at Massachusetts General Hospital. "Future research should assess whether flu vaccination is also associated with the rate of symptom progression in patients who already have Alzheimer's dementia."

The study -- which comes two years after UTHealth Houston researchers found a possible link between the flu vaccine and reduced risk of Alzheimer's disease -- analyzed a much larger sample than previous research, including 935,887 flu-vaccinated patients and 935,887 non-vaccinated patients.

During four-year follow-up appointments, about 5.1% of flu-vaccinated patients were found to have developed Alzheimer's disease. Meanwhile, 8.5% of non-vaccinated patients had developed Alzheimer's disease during follow-up.

These results underscore the strong protective effect of the flu vaccine against Alzheimer's disease, according to Bukhbinder and Schulz. However, the underlying mechanisms behind this process require further study.

"Since there is evidence that several vaccines may protect from Alzheimer's disease, we are thinking that it isn't a specific effect of the flu vaccine," said Schulz, who is also the Umphrey Family Professor in Neurodegenerative Diseases and director of the Neurocognitive Disorders Center at McGovern Medical School. "Instead, we believe that the immune system is complex, and some alterations, such as pneumonia, may activate it in a way that makes Alzheimer's disease worse. But other things that activate the immune system may do so in a different way -- one that protects from Alzheimer's disease. Clearly, we have more to learn about how the immune system worsens or improves outcomes in this disease."

Alzheimer's disease affects more than 6 million people living in the U.S., with the number of affected individuals growing due to the nation's aging population. Past studies have found a decreased risk of dementia associated with prior exposure to various adulthood vaccinations, including those for tetanus, polio, and herpes, in addition to the flu vaccine and others.

Additionally, as more time passes since the introduction of the COVID-19 vaccine and longer follow-up data becomes available, Bukhbinder said it will be worth investigating whether a similar association exists between COVID-19 vaccination and the risk of Alzheimer's disease.

Co-authors from McGovern Medical School included Omar Hasan, research coordinator in the Department of Neurology and student at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Kamal N. Phelps, fourth-year medical student; Srivathsan Ramesh, PhD, first-year resident in the Department of Orthopedic Surgery; and alumni Albert Amran, MD, and Ryan Coburn, MD. Co-authors from UTHealth Houston School of Biomedical Informatics included Yaobin Ling, graduate research assistant; Xiaoqian Jiang, PhD, the Christopher Sarofim Family Professor in Biomedical Informatics and Engineering; and Yejin Kim, PhD, assistant professor. Qian Xiao, PhD, MPH, assistant professor in the Department of Epidemiology and Disease Control with UTHealth School of Public Health, also co-authored the study.

https://www.sciencedaily.com/releases/2022/06/220624123814.htm

Sight problems may increase dementia risk in older adults

June 24, 2022

Science Daily/Taylor & Francis Group

Older adults with untreated sight conditions may be at increased risk of dementia, according to a new systematic review and meta-analysis of 16 studies involving 76,373 participants.

The results of the study, published in the peer-reviewed journal Aging and Mental Health, highlight a need for further research to examine the impact of correcting sight problems in older adults -- for example, with glasses or cataract surgery -- to prevent cognitive problems and dementia.

"This study is among the first to evaluate the association between sight problems and cognitive outcomes in older adults through a comprehensive examination of all available population-based studies in English. Our findings add to the growing evidence that fading eyesight is a risk factor for developing dementia," said lead author, Associate Professor Beibei Xu, from the Medical Informatics Center, at Peking University. "Although the reasons behind this remain unclear, it suggests that diagnosing and treating eye conditions may be beneficial -- both to improve a person's quality of life and also to potentially slow down or stop memory loss."

Nearly one million people are estimated to be living with dementia in the UK -- and that number is set to increase over the next few decades as the population ages. By 2050, it is predicted that this figure will have jumped to 1.6 million. The cost of dementia is expected to almost double in the same timeframe, from £25bn today to £47bn in 2050. The disease has a devastating impact on people's lives. As their disease progresses, they will experience greater memory loss and changes to their personality and behaviour. Ultimately, they will become completely dependent on others for their care.

The researchers included 16 studies including 76,373 participants, with five cross-sectional studies and 11 longitudinal studies published before April 2020. From these studies, the authors examined the relationship between visual impairment and cognitive outcomes in older adults. They found that:

• People with a sight problem had an increased risk of cognitive impairment and dementia, regardless of whether their visual impairment was self-reported or diagnosed using objective measures.

• The likelihood of having a cognitive impairment was 137% higher among people who had a sight problem compared to those who did not.

• People who had a sight problem at baseline had a 41% increased risk of developing cognitive impairment and a 44% increased risk of dementia, compared with those who did not.

"Finding ways to prevent or delay the onset of dementia could help reduce its devastating impact on the lives of affected individuals and their families, especially in light of the growing burden of the disease. Identifying modifiable risk factors is the first critical step for developing effective interventions to achieve this goal," says Beibei Xu. "Our new results highlight the importance of regular eye examinations for older adults -- enabling any potential problems with their vision to be spotted and treated early. They also suggest that any self-reported changes to a person's eyesight should not be ignored."

The authors (Gui-Ying Cao, Zi-Shuo Chen, Shan-Shan Yao, Kaipeng Wang, Zi-Ting Huang, He-Xuan Su, Yan Luo, Carson M De Fries, Yong-Hua Hu, and Beibei Xu) recommend future research is now warranted to examine the effectiveness of treating sight problems in older people to prevent cognitive impairment and dementia.

https://www.sciencedaily.com/releases/2022/06/220624104935.htm

Vitamin D deficiency can lead to dementia

June 14, 2022

Science Daily/University of South Australia

Dementia is one of the major causes of disability and dependency among older people worldwide, affecting thinking and behaviours as you age. But what if you could stop this degenerative disease in its tracks?

A world-first study from the University of South Australia could make this a reality as new genetic research shows a direct link between dementia and a lack of vitamin D.

Investigating the association between vitamin D, neuroimaging features, and the risk of dementia and stroke, the study found:

• low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke

• genetic analyses supported a causal effect of vitamin D deficiency and dementia.

• in some populations as much as 17 per cent of dementia cases might be prevented by increasing everyone to normal levels of vitamin D (50 nmol/L).

Dementia is a chronic or progressive syndrome that leads to deterioration in cognitive function. About 487,500 Australians live with dementia and it is the country's second leading cause of death. Globally, more than 55 million people have dementia with 10 million new cases diagnosed every year.

Supported by the National Health and Medical Research Council, the genetic study analysed data from 294,514 participants from the UK Biobank, examining the impact of low levels of vitamin D (25 nmol/L) and the risk of dementia and stroke. Nonlinear Mendelian randomisation (MR) -- a method of using measured variation in genes to examine the causal effect of a modifiable exposure on disease -- were used to test for underlying causality for neuroimaging outcomes, dementia, and stroke.

Senior investigator and Director of UniSA's Australian Centre for Precision Health, Professor Elina Hyppönen, says the findings are important for the prevention of dementia and appreciating the need to abolish vitamin D deficiency.

"Vitamin D is a hormone precursor that is increasingly recognised for widespread effects, including on brain health, but until now it has been very difficult to examine what would happen if we were able to prevent vitamin D deficiency," Prof Hyppönen says.

"Our study is the first to examine the effect of very low levels of vitamin D on the risks of dementia and stroke, using robust genetic analyses among a large population.

"In some contexts, where vitamin D deficiency is relatively common, our findings have important implications for dementia risks. Indeed, in this UK population we observed that up to 17 per cent of dementia cases might have been avoided by boosting vitamin D levels to be within a normal range."

The findings are incredibly significant given the high prevalence of dementia around the world.

"Dementia is a progressive and debilitating disease that can devastate individuals and families alike," Prof Hyppönen says.

"If we're able to change this reality through ensuring that none of us is severely vitamin D deficient, it would also have further benefits and we could change the health and wellbeing for thousands."

"Most of us are likely to be ok, but for anyone who for whatever reason may not receive enough vitamin D from the sun, modifications to diet may not be enough, and supplementation may well be needed."

https://www.sciencedaily.com/releases/2022/06/220614122721.htm

Recent study indicates high prevalence of recently defined non-Alzheimer's dementia

Results show prevalence of brain changes from LATE may be roughly 40% in older adults and as high as 50% in people with Alzheimer's disease.

June 13, 2022

Science Daily/University of Kentucky

Researchers from the University of Kentucky's Sanders-Brown Center on Aging say a paper recently published in Acta Neuropathologica is the most definitive assessment yet of the prevalence of a form of dementia classified in 2019 and now known as LATE. The results show that the prevalence of brain changes from LATE may be roughly 40% in older adults and as high as 50% in people with Alzheimer's disease.

"This is a fundamental question about any disease or condition, 'How commonly is it seen in peoples' brains?' and it is deceptively challenging to answer that question," said Pete Nelson, M.D., Ph.D., neuropathologist and the R.C. Durr Foundation Chair in Alzheimer's Disease at UK.

In 2019 Nelson and large group of international experts, working together, named this new form of dementia named limbic-predominant age-related TDP-43 encephalopathy (LATE).

The data for this new research came from 13 existing community and population-based study cohorts. The study included autopsy, genetic and clinical data from more than 6,000 brains. Five different countries across three continents are represented in the samples and data. The results indicated that more than a third of the brains had LATE pathology.

Symptoms of LATE mimic Alzheimer's disease by causing memory loss and problems with thinking and reasoning in old age. But researchers found the LATE-affected brain looks different from the Alzheimer's brain, and the therapies that may work for one probably would not work for the other.

Ten NIH-funded Alzheimer's Disease Research Centers, including University of Kentucky, were represented and worked together as a large coherent team. In addition to these U.S. centers, two cohorts from the United Kingdom, and one cohort each from Brazil, Austria, and Finland took part in this study.

"Not only is the size of this combined analysis important but also the fact that those who took part in the studies leading to brain donation were derived from longitudinal studies in researched populations. Due to this we can say more about the contribution of LATE to dementia in older populations. This is quite different from most research which is effectively from individuals without that anchoring," said Carol Brayne, M.D., British academic and Professor of Public Health Medicine at the University of Cambridge. "Given older ages are when dementia is most common, the LATE findings are particularly important. Although there are many differences between the studies that are combined here -- from design to methodologies -- they all reveal the importance of LATE and suggest our findings will be relevant beyond any individual country or region of the world."

In addition to the University of Kentucky, other U.S. Alzheimer's Disease Research Centers involved in this work include Northwestern University Medical Center, Rush University Medical Center, Mayo Clinic (both MN and FL campuses), Duke University, University of California (Davis), University of California (Irvine), University of California (San Francisco), University of Washington, and Stanford University. Nelson says that ultimately this study helps indicate that LATE is an extremely common contributor to the devastating clinical syndrome that is often referred to as Alzheimer's disease or dementia. While looking at the findings, Nelson and the other researchers indicated that LATE was even more common in brains with severe Alzheimer's disease neuropathologic change (ADNC) -- over half of severe ADNC cases also had LATE.

With the first clinical trial in the world for LATE currently underway at the University of Kentucky, and attention turning towards preventing LATE and Alzheimer's, Nelson says basic information gained through studies like this one is crucial. "It helps us frame key questions like, 'Who should be recruited into a research study? What should we be looking for?' It can also help guide us on how to better study LATE and Alzheimer's disease when those two brain diseases are so often present in the same person."

While progress is being made, there still are many knowledge gaps.

"We need more information in more diverse cohorts. People with African or Asian heritage were relatively under-sampled in this study. So far, it does not appear that people with different ethnic backgrounds have differing risk for LATE but further work is required in this important area," said Nelson.

https://www.sciencedaily.com/releases/2022/06/220613111434.htm

Multiple heart-related conditions linked to triple dementia risk, regardless of genetics

Having multiple conditions that affect the heart are linked to a greater risk of dementia than having high genetic risk, according to a largescale new study

June 8, 2022

Science Daily/University of Exeter

Having multiple conditions that affect the heart are linked to a greater risk of dementia than having high genetic risk, according to a largescale new study.

Led by Oxford University and the University of Exeter, the study is among the largest ever to examine the link between several heart-related conditions and dementia, and one of the few to look at the complex issue of multiple health conditions.

Published in The Lancet Healthy Longevity, the paper looked at data from more than 200,000 people, aged 60 or above, and of European ancestry in UK Biobank. The international research team identified those who had been diagnosed with the cardiometabolic conditions diabetes, stroke, or a heart attack, or any combination of the three, and those who went on to develop dementia.

Within this study population, the researchers found that the more of these three conditions a person had, the higher their risk of dementia. People who had all three conditions were three times more likely to develop dementia than people who had a high genetic risk.

Dr Xin You Tai, Lead Author and Doctoral Student at University of Oxford, said: "Dementia is a major global issue, with predictions that 135 million worldwide will have the devastating condition by 2050. We found that having such heart-related conditions is linked to dementia risk to a greater extent than genetic risk. So whatever genetic risk you were born with, you can potentially make a big impact on reducing risk of dementia by looking after heart and metabolic health throughout life."

The team, which included the universities of Glasgow and Michigan, found that nearly 20,000 of the UK Biobank participants they studied had been diagnosed with one of the three conditions. Just over 2,000 had two conditions, and 122 had all three.

Professor David Llewellyn, Senior Author, Professor of Clinical Epidemiology and Clinical Health at the University of Exeter, said: "Many studies look at the risk of a single condition in relation to dementia, but health is more complex than that. We know that many patients actually have a range of conditions. Our study tells us that for people who have a diagnosis of diabetes, stroke or a heart attack it is particularly important to look after their health and ensure they are on the right treatment, to prevent further problems as well as to reduce their dementia risk."

The team divided the 200,000 participants into three categories of genetic risk from high to low, based on a comprehensive risk score reflecting multiple genetic risk traits relevant to individuals of European ancestry. They also had brain imaging data for over 12,000 participants, and found widespread damage across the brain for those with more than one cardiometabolic condition. By contrast, high genetic risk was linked to deterioration only in specific parts of the brain.

Dr Kenneth M. Langa, Study Co-author, Professor of Medicine at the University of Michigan and Veteran Affairs Ann Arbor Healthcare System, said: "Our research indicates that protecting the heart throughout life likely also has significant benefits for the brain. To look after your heart, you can engage in regular exercise, eat a healthy diet and do everything possible to ensure blood pressure, blood sugar and cholesterol levels fall within guidelines."

Dr Sara Imarisio, Head of Research at Alzheimer's Research UK, said: "The evidence is clear that what's good for your heart is also good for your head. A person's risk of developing dementia is a complex mix of their age, their genes, and aspects of their lifestyle. In this study, researchers looked at data from a population of 60 years and older, including whether they had particular heart conditions, information about their genetics, and how these affected their risk of developing dementia. They found that people with multiple heart health conditions were even more likely to develop dementia than people who had an increased risk of Alzheimer's disease due to their genetics

"These findings reiterate the importance of treating the causes of poor heart health, not just for its own sake, but also the added benefit in terms of reducing the number of dementia cases. From the generosity of our supporters who enabled us to fund this work, to the selflessness of the volunteers that made it possible, we want to say thank you, without you research like this cannot take place.

"If anyone is worried about the health of your heart or your brain, please speak to your doctor."

https://www.sciencedaily.com/releases/2022/06/220608184340.htm

Social isolation is directly associated with later dementia

June 8, 2022

Science Daily/University of Warwick

Interdisciplinary study shows changes to brain structures associated with memory and cognitive function are directly linked to social isolation. The data shows that socially isolated people are 26% more likely to develop later dementia. The study has implications for health and social care policy, in the wake of the COVID-19 pandemic.

Social isolation is directly linked with changes in the brain structures associated with memory, making it a clear risk factor for dementia, scientists have found.

Setting out to investigate how social isolation and loneliness were related to later dementia, researchers at the University of Warwick, University of Cambridge and Fudan University used neuroimaging data from more than 30,000 participants in the UK Biobank data set. Socially isolated individuals were found to have lower gray matter volumes of brain regions involved in memory and learning.

The results of the study are published online today (June 8, 2022) in Neurology, the medical journal of the American Academy of Neurology, in a paper entitled "Associations of social isolation and loneliness with later dementia" by Shen, Rolls, Cheng, Kang, Dong, Xie, Zhao, Sahakian and Feng.

Based on data from the UK Biobank, an extremely large longitudinal cohort, the researchers used modelling techniques to investigate the relative associations of social isolation and loneliness with incident all-cause dementia. After adjusting for various risk factors (including socio-economic factors, chronic illness, lifestyle, depression and APOE genotype), socially isolated individuals were shown to have a 26% increased likelihood of developing dementia.

Loneliness was also associated with later dementia, but that association was not significant after adjusting for depression, which explained 75% of the relationship between loneliness and dementia. Therefore, relative to the subjective feeling of loneliness, objective social isolation is an independent risk factor for later dementia. Further subgroup analysis showed that the effect was prominent in those over 60 years old.

Professor Edmund Rolls, neuroscientist from the University of Warwick Department of Computer Science, said: "There is a difference between social isolation, which is an objective state of low social connections, and loneliness, which is subjectively perceived social isolation.

"Both have risks to health but, using the extensive multi-modal data set from the UK Biobank, and working in a multidisciplinary way linking computational sciences and neuroscience, we have been able to show that it is social isolation, rather than the feeling of loneliness, which is an independent risk factor for later dementia. This means it can be used as a predictor or biomarker for dementia in the UK.

"With the growing prevalence of social isolation and loneliness over the past decades, this has been a serious yet underappreciated public health problem. Now, in the shadow of the COVID-19 pandemic there are implications for social relationship interventions and care -- particularly in the older population."

Professor Jianfeng Feng, from the University of Warwick Department of Computer Science, said: "We highlight the importance of an environmental method of reducing risk of dementia in older adults through ensuring that they are not socially isolated. During any future pandemic lockdowns, it is important that individuals, especially older adults, do not experience social isolation."

Professor Barbara J Sahakian, of the University of Cambridge Department of Psychiatry, said: "Now that we know the risk to brain health and dementia of social isolation, it is important that the government and communities take action to ensure that older individuals have communication and interactions with others on a regular basis."

https://www.sciencedaily.com/releases/2022/06/220608161434.htm

How sleep builds relational memory

Learning connections between unrelated items requires neurons and brain circuits representing these items to be active and interact during sleep

May 31, 2022

Science Daily/University of California - San Diego

Relational memory is the ability to remember arbitrary or indirect associations between objects, people or events, such as names with faces, where you left your car keys and whether you turned off the stove after cooking but before you left the house.

Previous research has established that animal and human memory benefits from sufficient, quality sleep. In a new study, published May 25, 2022 in the Journal of Neuroscience, Maxim Bazhenov, PhD, professor of medicine at University of California San Diego School of Medicine, and Timothy Tadros, a graduate student in his lab, describe the underlying mechanisms that strengthen or create new relational memories during sleep.

The authors developed an artificial model of two regions of the brain: the thalamic (involved in earlier sensory processing) and the cortical (involved in memory, learning and decision-making). The model was capable of simulating two major brain states: awake when neurons are spontaneously active and optimized to process sensory input and deep sleep when intrinsic oscillations of electrical activity are generated, such as slow-waves.

The properties of the network model could be changed to promote transitions between awake and asleep activity, similar to what the biological brain does every day.

In the cortical region, connections between the neurons were permitted to become stronger or weaker based on their activity, known as synaptic plasticity, which reflects the primary known biological mechanism for how memories are formed or erased.

"We modelled the cortex after visual processing, with one cortical layer representing primary visual cortex and another cortical layer representing associative cortex," said Tadros. "Every time one sees the same object, roughly the same neurons in the visual cortex would be active. If a person sees two objects in the same context, then these associations might be learned in the associative cortex by strengthening connections between neurons that represent each of the two objects."

The scientists trained the network in its awake mode to learn such direct associations, such as A+B or B+C but not A+C, then discovered that in the sleep mode, the model formed indirect associations: A+C.

"This happened because during sleep the neurons representing all three related items (A, B and C) spontaneously fired in close temporal order, a phenomenon called sleep replay, which triggered synaptic plasticity and led to formation of strong synaptic connections between all these neurons," said Bazhenov. "Therefore, after sleep, activating any one group, such as A, activated all other related groups, such as B and C."

While primarily conceptual, the researchers said the work has real-world implications.

"One important real-world impact of the study is in informing future studies of disease, such as schizophrenia and autism spectrum disorder," said Bazhenov. "Studies have shown that people with these conditions perform worse on relational memory tasks and also have disrupted sleep, specifically slow-wave sleep.

"Our study suggests that focusing on improving slow-wave sleep in order to alleviate some of the cognitive symptoms associated with these conditions may be a more fruitful path forward than focusing on the cognitive symptoms exclusively."

The authors also noted that memory function and sleep quality decline with age, but current or new technologies that augment sleep oscillations may help protect and improve memory function in older adults.

https://www.sciencedaily.com/releases/2022/05/220531111821.htm

Seven healthy habits linked to lower risk of dementia in those with genetic risk

May 25, 2022

Science Daily/American Academy of Neurology

Seven healthy habits and lifestyle factors may play a role in lowering the risk of dementia in people with the highest genetic risk, according to research published in the May 25, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The seven cardiovascular and brain health factors, known as the American Heart Association's Life's Simple 7, are: being active, eating better, losing weight, not smoking, maintaining a healthy blood pressure, controlling cholesterol, and reducing blood sugar.

"These healthy habits in the Life's Simple 7 have been linked to a lower risk of dementia overall, but it is uncertain whether the same applies to people with a high genetic risk," said study author Adrienne Tin, PhD, of the University of Mississippi Medical Center in Jackson. "The good news is that even for people who are at the highest genetic risk, living by this same healthier lifestyle are likely to have a lower risk of dementia."

The study looked at 8,823 people with European ancestry and 2,738 people with African ancestry who were followed for 30 years. People had an average age of 54 at the beginning of the study.

Study participants reported their levels in all seven health factors. Total scores ranged from 0 to 14, with 0 representing the most unhealthy score and 14 representing the most healthy score. The average score among those with European ancestry was 8.3 and the average score amongst those with African ancestry was 6.6.

Researchers calculated genetic risk scores at the start of the study using genome-wide statistics of Alzheimer's disease, which have been used to study the genetic risk for dementia.

Participants with European ancestry were divided into five groups and those with African ancestry were divided into three groups based on genetic risk scores. The group with the highest genetic risk included people who had at least one copy of the APOE gene variant associated with Alzheimer's disease, APOE e4. Of those with European ancestry, 27.9% had the APOE e4 variant, while of those who had African ancestry, 40.4% had the APOE e4 variant. The group with the lowest risk had the APOE e2 variant, which has been associated with a decreased risk of dementia.

By the end of the study, 1,603 people with European ancestry developed dementia and 631 people with African ancestry developed dementia.

For people with European ancestry, researchers found that people with the highest scores in the lifestyle factors had a lower risk of dementia across all five genetic risk groups, including the group with the highest genetic risk of dementia. For each one-point increase in the lifestyle factor score, there was a 9% lower risk of developing dementia. Among those with European ancestry, compared with the low category of the lifestyle factor score, the intermediate and high categories were associated with 30% and 43% lower risk for dementia, respectively. Among those with African ancestry, the intermediate and high categories were associated with 6% and 17% lower risk for dementia, respectively.

Among people with African ancestry, researchers found a similar pattern of declining dementia risk across all three groups among those with higher scores on the lifestyle factors. But researchers said the smaller number of participants in this group limited the findings, so more research is needed.

"Larger sample sizes from diverse populations are needed to get more reliable estimates of the effects of these modifiable health factors on dementia risk within different genetic risk groups and ancestral backgrounds," Tin said.

https://www.sciencedaily.com/releases/2022/05/220525163821.htm

Insomnia in midlife may manifest as cognitive problems in retirement age

May 20, 2022

Science Daily/University of Helsinki

The Helsinki Health Study at the University of Helsinki investigated the development of insomnia symptoms in midlife and their effects on memory, learning ability and concentration after retirement. The follow-up period was 15-17 years.

According to the study, long-term insomnia symptoms and later poorer cognitive functioning have a clear connection.

"The findings indicate that severe insomnia symptoms were associated with worse cognitive function among those who were on statutory pension," says Doctoral Researcher Antti Etholén, describing the results of the study.

The study also found that the memory problems, and problems in learning ability and concentration increased as the insomnia symptoms were prolonged.

Sleeping well already in middle age

Prior research has shown that there are a number of mechanisms that can explain how sleep can affect cognitive functioning. What makes the recently published study exceptional is the long follow-up period for insomnia symptoms.

Among other things, the study demonstrated that if insomnia symptoms eased over the years, cognitive functioning was also found to be better at retirement age compared to the problems persisting.

According to the researchers, long-lasting insomnia symptoms should be considered as risk factors for poor cognitive functioning.

"Based on our findings, early intervention tackling insomnia symptoms, or measures aimed at improving the quality of sleep would be justified," says Professor Tea Lallukka.

There are many ways to improve the quality of sleep, including the regularity of the sleep rhythm, the appropriate temperature and brightness of the sleeping environment, and the optimal timing of physical exercise, coffee consumption and eating.

However, Lallukka believes that intervention studies are still needed to ascertain the effects of measures in support of good sleep.

"In subsequent studies, it would be interesting to shed further light on, for example, whether the treatment of insomnia can also slow down the development of memory disorders," Lallukka says. She points outs that only self-reported memory symptoms could be taken into consideration in the present study.

https://www.sciencedaily.com/releases/2022/05/220520101346.htm

How cranberries could improve memory and ward off dementia

May 19, 2022

Science Daily/University of East Anglia

Adding cranberries to your diet could help improve memory and brain function, and lower 'bad' cholesterol -- according to new research from the University of East Anglia (UK).

A new study published today highlights the neuroprotective potential of cranberries.

The research team studied the benefits of consuming the equivalent of a cup of cranberries a day among 50 to 80-year-olds.

They hope that their findings could have implications for the prevention of neurodegenerative diseases such as dementia.

Lead researcher Dr David Vauzour, from UEA's Norwich Medical School, said: "Dementia is expected to affect around 152 million people by 2050. There is no known cure, so it is crucial that we seek modifiable lifestyle interventions, such as diet, that could help lessen disease risk and burden.

"Past studies have shown that higher dietary flavonoid intake is associated with slower rates of cognitive decline and dementia. And foods rich in anthocyanins and proanthocyanidins, which give berries their red, blue, or purple colour, have been found to improve cognition.

"Cranberries are rich in these micronutrients and have been recognized for their antioxidant and anti-inflammatory properties.

"We wanted to find out more about how cranberries could help reduce age-related neurodegeneration."

The research team investigated the impact of eating cranberries for 12 weeks on brain function and cholesterol among 60 cognitively healthy participants.

Half of the participants consumed freeze-dried cranberry powder, equivalent to a cup or 100g of fresh cranberries, daily. The other half consumed a placebo.

The study is one of the first to examine cranberries and their long-term impact on cognition and brain health in humans.

The results showed that consuming cranberries significantly improved the participants' memory of everyday events (visual episodic memory), neural functioning and delivery of blood to the brain (brain perfusion).

Dr Vauzour said: "We found that the participants who consumed the cranberry powder showed significantly improved episodic memory performance in combination with improved circulation of essential nutrients such as oxygen and glucose to important parts of the brain that support cognition -- specifically memory consolidation and retrieval.

"The cranberry group also exhibited a significant decrease in LDL or 'bad' cholesterol levels, known to contribute to atherosclerosis -- the thickening or hardening of the arteries caused by a build-up of plaque in the inner lining of an artery. This supports the idea that cranberries can improve vascular health and may in part contribute to the improvement in brain perfusion and cognition.

"Demonstrating in humans that cranberry supplementation can improve cognitive performance and identifying some of the mechanisms responsible is an important step for this research field.

"The findings of this study are very encouraging, especially considering that a relatively short 12-week cranberry intervention was able to produce significant improvements in memory and neural function," he added.

"This establishes an important foundation for future research in the area of cranberries and neurological health."

https://www.sciencedaily.com/releases/2022/05/220519081109.htm

Quantifying cognitive decline in dogs could help humans with Alzheimer's disease

May 9, 2022

Science Daily/North Carolina State University

Researchers have found that a suite of complementary tests can quantify changes in dogs suspected of suffering from cognitive decline. The approach could not only aid owners in managing their elderly canine's care, but could also serve as a model for evaluating cognitive decline progression in -- and treatments for -- humans with Alzheimer's disease.

Canine cognitive dysfunction syndrome (CCDS) is similar to Alzheimer's disease in humans in that cognitive decline is associated with the development of amyloid plaques as well as cortical atrophy, a progressive degeneration of brain tissue. CCDS is also challenging to diagnose. Traditionally, CCDS is diagnosed based on ruling out any obvious physical conditions and an owner's answers to a questionnaire.

"One problem with the current approach is that questionnaires only capture a constellation of home behaviors," says Natasha Olby, the Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at North Carolina State University and co-senior author of a paper describing the work. "There can be other reasons for what an owner may perceive as cognitive decline -- anything from an undiagnosed infection to a brain tumor."

Olby and co-senior author Margaret Gruen, assistant professor of behavioral medicine at NC State, wanted to determine whether cognitive function could be accurately quantified in dogs.

"Our goal was to bring together multiple tools in order to get a more complete picture of how CCDS presents in dogs," Gruen says.

To that end, the researchers recruited 39 dogs from 15 breeds. All of them were in the senior and geriatric age range, but in good health overall. A dog is considered "senior" if it is in the last 25% of its expected life span based on breed and size, and geriatric beyond that.

The dogs underwent physical and orthopedic exams, as well as lab work that included a blood test that is a marker of neuronal death. Their owners filled out two commonly used diagnostic questionnaires, and then the dogs participated in a series of cognitive tests designed to assess executive function, memory and attention.

"The approach we took isn't necessarily designed to be diagnostic; instead, we want to use these tools to be able to identify dogs at an early stage and be able to follow them as the disease progresses, quantifying the changes," Olby says.

The team found that cognitive and blood test results correlated well with the questionnaire scores, suggesting that a multi-dimensional approach can be used to quantify cognitive decline in aging dogs.

"Being able to diagnose and quantify CCDS in a way that is clinically safe and relevant is a good first step toward being able to work with dogs as a model for Alzheimer's disease in humans," Olby says. "Many of the current models of Alzheimers disease -- in rodents, for example -- are good for understanding physiological changes, but not for testing treatments."

"Dogs live in our homes and develop naturally occurring disease just like we do," Gruen says. "These findings show promise for both dogs and humans in terms of improving our understanding of disease progression as well as for potentially testing treatments."

The work appears in the Journal of Alzheimer's Disease. NC State postdoctoral fellows Gilad Fefer and Wojciech K. Panek are co-first authors of the work.

https://www.sciencedaily.com/releases/2022/05/220509150745.htm

Stressed' cells offer clues to eliminating build-up of toxic proteins in dementia

May 6, 2022

Science Daily/University of Cambridge

It's often said that a little stress can be good for you. Now scientists have shown that the same may be true for cells, uncovering a newly-discovered mechanism that might help prevent the build-up of tangles of proteins commonly seen in dementia.

A characteristic of diseases such as Alzheimer's and Parkinson's -- collectively known as neurodegenerative diseases -- is the build-up of misfolded proteins. These proteins, such as amyloid and tau in Alzheimer's disease, form 'aggregates' that can cause irreversible damage to nerve cells in the brain.

Protein folding is a normal process in the body, and in healthy individuals, cells carry out a form of quality control to ensure that proteins are correctly folded and that misfolded proteins are destroyed. But in neurodegenerative diseases, this system becomes impaired, with potentially devastating consequences.

As the global population ages, an increasing number of people are being diagnosed with dementia, making the search for effective drugs ever more urgent. However, progress has been slow, with no medicines yet available that can prevent or remove the build-up of aggregates.

In a study published today in Nature Communications, a team led by scientists at the UK Dementia Research Institute, University of Cambridge, has identified a new mechanism that appears to reverse the build-up of aggregates, not by eliminating them completely, but rather by 'refolding' them.

"Just like when we get stressed by a heavy workload, so, too, cells can get 'stressed' if they're called upon to produce a large amount of proteins," explained Dr Edward Avezov from the UK Dementia Research Institute at the University of Cambridge.

"There are many reasons why this might be, for example when they are producing antibodies in response to an infection. We focused on stressing a component of cells known as the endoplasmic reticulum, which is responsible for producing around a third of our proteins -- and assumed that this stress might cause misfolding."

The endoplasmic reticulum (ER) is a membrane structure found in mammalian cells. It carries out a number of important functions, including the synthesis, folding, modification and transport of proteins needed on the surface or outside the cell. Dr Avezov and colleagues hypothesised that stressing the ER might lead to protein misfolding and aggregation by diminishing its ability to function correctly, leading to increased aggregation.

They were surprised to discover the opposite was true.

"We were astonished to find that stressing the cell actually eliminated the aggregates -- not by degrading them or clearing them out, but by unravelling the aggregates, potentially allowing them to refold correctly," said Dr Avezov.

"If we can find a way of awakening this mechanism without stressing the cells -- which could cause more damage than good -- then we might be able to find a way of treating some dementias."

The main component of this mechanism appears to be one of a class of proteins known as heat shock proteins (HSPs), more of which are made when cells are exposed to temperatures above their normal growth temperature, and in response to stress.

Dr Avezov speculates that this might help explain one of the more unusual observations within the field of dementia research. "There have been some studies recently of people in Scandinavian countries who regularly use saunas, suggesting that they may be at lower risk of developing dementia. One possible explanation for this is that this mild stress triggers a higher activity of HSPs, helping correct tangled proteins."

One of the factors that has previous hindered this field of research has been the inability to visualise these processes in live cells. Working with teams from Pennsylvania State University and the University of Algarve, the team has developed a technique that allows them to detect protein misfolding in live cells. It relies on measuring light patterns of a glowing chemical over a scale of nanoseconds -- one billionth of a second.

"It's fascinating how measuring our probe's fluorescence lifetime on the nanoseconds scale under a laser-powered microscope makes the otherwise invisible aggregates inside the cell obvious," said Professor Eduardo Melo, one of the leading authors, from the University of Algarve, Portugal.

https://www.sciencedaily.com/releases/2022/05/220506102618.htm

Promising treatment for dementia

Sodium selenate slows behavioural variant frontotemporal dementia -- second most common dementia in under 60s

May 5, 2022

Science Daily/Monash University

A Monash University led study has found a promising new treatment for patients with behavioural variant frontotemporal dementia, the second most common form of dementia in the under 60s -- resulting in a stabilising of what would normally be escalating behavioural issues, and a slowing of brain shrinkage due to the disease. It is the second clinical trial to show that the drug, sodium selenate, may slow cognitive decline and neurodegenerative damage that is the hallmark of many dementias including Alzheimer's Disease.

Behavioural variant frontotemporal dementia (bvFTD) is a rapidly progressing destructive disease and can occur in people as young as 35 years of age. It is characterised by behavioural disturbances and personality changes and can be highly disruptive and distressing for both patients and their families. Currently there are no treatments or cures for bvFTD and typical survival is 5-7 years from diagnosis.

The Phase 1 trial run in conjunction with the Royal Melbourne Hospital, the only one in Australia targeting non-genetic bvFTD, and one of a handful worldwide, showed that the drug, sodium selenate is safe and well-tolerated in patients with bvFTD over a period of 12 months. Importantly, the majority of patients receiving sodium selenate showed no change in their cognitive or behavioural symptoms, and reduced rates of brain atrophy over the trial period. The results from the trial, led by Dr Lucy Vivash, from the Monash University's Department of Neuroscience, have just been published in the journal, Alzheimer's and Dementia: Translational Research and Clinical Interventions.

In almost half of the cases with bvFTD, the damage to the neurons in the brain is caused by the build-up of a protein called tau. This protein is a major target for research in the prevention and treatment of Alzheimer's and other dementias, as a way to reverse the neurodegeneration caused by this tau accumulation.

According to Dr Vivash, sodium selenate upregulates an enzyme in the brain that effectively breaks down the tau protein. "We have previously shown, in a Phase 2 trial, that sodium selenate given to patients with mild to moderate Alzheimer's Disease resulted in less neurodegeneration than in those who did not," she said. Importantly those patients in the trial with higher levels of selenium, a breakdown product of sodium selenate, in their bloodstream showed less cognitive decline.

The research group is now conducting a larger study at many hospitals across Australia and New Zealand to further test whether this drug is beneficial for patients with bvFTD.

https://www.sciencedaily.com/releases/2022/05/220505102147.htm

Higher antioxidant levels linked to lower dementia risk

May 4, 2022

Science Daily/American Academy of Neurology

People with higher levels of antioxidants in their blood may be less likely to develop dementia, according to a study published in the May 4, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study found that people with the highest levels of the antioxidants lutein and zeaxanthin and beta-cryptoxanthin in their blood were less likely to develop dementia decades later than people with lower levels of the antioxidants. Lutein and zeaxanthin are found in green, leafy vegetables such as kale, spinach, broccoli and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines and persimmons.

"Extending people's cognitive functioning is an important public health challenge," said study author May A. Beydoun, PhD, MPH, of the National Institutes of Health's National Institute on Aging in Baltimore, Maryland. "Antioxidants may help protect the brain from oxidative stress, which can cause cell damage. Further studies are needed to test whether adding these antioxidants can help protect the brain from dementia."

The study involved 7,283 people who were at least 45 years old at the beginning of the study. They had a physical exam, interview and blood tests for antioxidant levels at the beginning of the study. They were then followed for an average of 16 years to see who developed dementia.

The participants were divided into three groups based on their levels of antioxidants in the blood. People with the highest amounts of lutein and zeaxanthin were less likely to develop dementia than those with lower levels. Every standard deviation increase in lutein and zeaxanthin levels, approximately 15.4 micromols/liter, was associated with a 7% decrease in risk of dementia. For beta-cryptoxanthin, every standard deviation increase in levels, approximately 8.6 micromols/liter, was associated with a 14% reduced risk of dementia.

"It's important to note that the effect of these antioxidants on the risk of dementia was reduced somewhat when we took into account other factors such as education, income and physical activity, so it's possible that those factors may help explain the relationship between antioxidant levels and dementia," Beydoun said.

A limitation of the study is that antioxidant levels were based on one measurement of blood levels and may not reflect people's levels over their lifetime.

https://www.sciencedaily.com/releases/2022/05/220504170826.htm