Remembering faces and names can be improved during sleep

Research finds memory reactivation — combined with quality sleep — is key

January 12, 2022

Science Daily/Northwestern University

For those who rarely forget a face, but struggle with names, the remedy for boosting learning may as near as your pillow.

New research by Northwestern University is the first to document the effect reactivating memory during sleep has on face-name learning.

The researchers found that people's name recall improved significantly when memories of newly learned face-name associations were reactivated while they were napping. Key to this improvement was uninterrupted deep sleep.

"It's a new and exciting finding about sleep, because it tells us that the way information is reactivated during sleep to improve memory storage is linked with high-quality sleep," said lead author Nathan Whitmore, a Ph.D. candidate in the Interdepartmental Neuroscience Program at Northwestern.

The paper, "Targeted memory reactivation of face-name learning depends on ample and undisturbed slow-wave sleep," will publish Jan. 12 in the Nature partner journal NPJ: Science of Learning.

The paper's senior author is Ken Paller, professor of psychology and director of the Cognitive Neuroscience Program at Weinberg College of Arts and Sciences at Northwestern. The paper was also co-authored by Adrianna Bassard, Ph.D. candidate in psychology at Northwestern.

The research team found that for study participants with EEG measures (a recording of electrical activity of the brain picked up by electrodes on the scalp) that indicated disrupted sleep, the memory reactivation didn't help and may even be detrimental. But in those with uninterrupted sleep during the specific times of sound presentations, the reactivation led to a relative improvement averaging just over 1.5 more names recalled.

The study was conducted on 24 participants, aged 18-31 years old, who were asked to memorize the faces and names of 40 pupils from a hypothetical Latin American history class and another 40 from a Japanese history class. When each face was shown again, they were asked to produce the name that went with it. After the learning exercise, participants took a nap while the researchers carefully monitored brain activity using EEG measurements. When participants reached the N3 "deep sleep" state, some of the names were softly played on a speaker with music that was associated with one of the classes.

When participants woke up, they were retested on recognizing the faces and recalling the name that went with each face.

The researchers say the finding on the relationship between sleep disruption and memory accuracy is noteworthy for several reasons.

"We already know that some sleep disorders like apnea can impair memory," said Whitmore. "Our research suggests a potential explanation for this -- frequent sleep interruptions at night might be degrading memory."

The lab is in the midst of a follow-up study to reactivate memories and deliberately disrupt sleep in order to learn more about the relevant brain mechanisms.

"This new line of research will let us address many interesting questions -- like whether sleep disruption is always harmful or whether it could be used to weaken unwanted memories," said Paller, who also holds the James Padilla Chair in Arts & Sciences at Northwestern. "At any rate, we are increasingly finding good reasons to value high-quality sleep."

https://www.sciencedaily.com/releases/2022/01/220112094000.htm

Keeping active through varied activities can reduce risk of developing dementia

December 17, 2021

Science Daily/Simon Fraser University

Older adults who participate in a variety of different activities are able to reduce their risk of developing dementia, according to a new study from researchers at Simon Fraser University.

The team found that engaging in a combination of hobbies, such as light exercise and connecting with loved ones, can reduce memory decline in adults between the ages of 65 and 89 more than any individual activity.

Their findings, published in the journal Aging show that the effects of engaging in a combination of activities increased with age and was more impactful than historical factors such as education level or baseline memory.

The study examined data from the National Institute on Aging's Health and Retirement Study and included 3,210 participants aged 65 to 89. Study participants were asked how often they engaged in 33 activities from 'never' to 'at least once a month' to 'several times a month' up to 'daily'.

Researchers created a machine learning model to analyze the activities' impact on memory. The activities ranged from hobbies such as baking or cooking, reading, playing cards and games to walking for 20 minutes, or socializing with family and friends through letters, email, phone calls or in-person visits.

"Our study results show that the risk of developing dementia can be reduced through a combination of active, daily activities -- things like using a computer and playing word games," says study co-author Sylvain Moreno, an associate professor at SFU's School of Interactive Arts and Technology (SIAT) and CEO/scientific director of the Digital Health Circle, based at SFU.

"Scientists believed that genetics were the main factor influencing cognitive health but our findings show the reverse. With age, your choice of daily activities is more important than your genetics or your current cognitive skills," Moreno adds.

The researchers suggest their study results could have a significant impact on aging health policies, including promoting new social prescribing programs to help older adults keep mentally active into their senior years.

Social prescribing involves connecting older adults to a range of activities in the community such as gardening, art classes or volunteering.

Older adults are more at risk of developing dementia and other neurodegenerative disorders for which there is no cure, which is why prevention is so important.

"Today, around 55 million people have dementia and this number will almost triple by 2050 with an aging population," says Moreno. "Care for patients with dementia is challenging, labour-intensive, and chronic, which generates high costs for health systems."

Their research demonstrates that strategies for prevention are effective and a social prescribing approach to healthcare can help people maintain healthy cognitive function as they age.

https://www.sciencedaily.com/releases/2021/12/211217102857.htm

Cataract surgery linked with lessened dementia risk

December 6, 2021

Science Daily/University of Washington School of Medicine/UW Medicine

Cataracts affect most older adults at risk for dementia, and now researchers are finding strong evidence that cataract surgery is associated with a lower risk of developing dementia.

The Adult Changes in Thought (ACT) study is a long-standing, Seattle-based observational study at Kaiser Permanente Washington of more than 5,000 participants older than 65. Based on the longitudinal data of over 3,000 ACT study participants, researchers have now found that subjects who underwent cataract surgery had nearly 30% lower risk of developing dementia from any cause compared with those who did not. This lowered risk persisted for at least a decade after surgery. Cataract surgery was also associated with lower risk of Alzheimer disease dementia specifically. The results were reported Dec. 6 in JAMA Internal Medicine.

Lead researcher Dr. Cecilia S Lee, associate professor and Klorfine Family Endowed Chair in ophthalmology at the University of Washington School of Medicine, said the observational study adjusted for a number of potential confounders, yet still yielded a strong association.

"This kind of evidence is as good as it gets in epidemiology," Lee said. "This is really exciting because no other medical intervention has shown such a strong association with lessening dementia risk in older individuals."

The mechanisms by which cataract surgery and lessened dementia risk are associated was not determined in this study. Researchers hypothesize that people may be getting higher quality sensory input after cataract surgery, which might have a beneficial effect in reducing the risk of dementia.

"These results are consistent with the notion that sensory input to the brain is important to brain health," said co-author Dr. Eric B. Larson, a principal investigator of the ACT study, and senior investigator at Kaiser Permanente Washington Health Research Institute.

Lee said another hypothesis is that after cataract surgery, people are getting more blue light.

"Some special cells in the retina are associated with cognition and regulate sleep cycles, and these cells respond well to blue light," she said, "Cataracts specifically block blue light, and cataract surgery could reactivate those cells."

The study results highlight a strong case for further research on the eye-brain connection in dementia. Previous studies by Lee's group at the UW have shown a strong link between other retinal diseases, such as age-related macular degeneration, and the development of Alzheimer disease and dementia. Subjects with macular degeneration or other retinal degenerative diseases are more likely to develop dementia, In the current study, subjects undergoing vision-improving cataract surgery had lower risk of developing dementia. Further understanding the connection between the aging eye and brain may offer insights and potential therapies to slow or prevent age-related dementia.

The study: Researchers tracked participants diagnosed with a cataract or glaucoma but who did not have dementia at the time they volunteered for the study. Participants also did not have cataract surgery at the time of enrollment. Participants are evaluated every two years for cognitive abilities based on the Cognitive Abilities Screening Instrument, which scores in a range from 0-100. Participants with scores less than 85 undergo further neurological tests.

During follow-up of 3,038 participants (an average of 7.8 years per person), 853 subjects developed dementia, with 709 cases of Alzheimer disease. Approximately half of the participants (1,382 individuals or 45%) had cataract surgery. Analysis for risk of developing dementia showed that subjects who had undergone cataract surgery in either eye were about 30% less likely to develop any form of dementia for at least 10 years after their surgery.

Analysis was adjusted for an extensive list of factors including health-related confounders. Cataract surgery could appear to have a protective effect due to a healthy patient bias, where participants who underwent cataract surgery might have been healthier and at lower dementia risk. Researchers performed analyses to account for several types of potential bias, but still found strong associations when these factors were accounted for.

Researchers excluded eye surgeries in the two years prior to dementia diagnosis to rule out the possibility that people with cognitive decline prior to dementia diagnosis may have been less conscious of vision issues, and thus less likely to have undergone cataract surgery. Even with this group excluded, the researchers found lower risks of dementia associated with cataract surgery.

As another control, participants were also evaluated for a possible link between another type of eye surgery (glaucoma surgery) and dementia. In this case, no association was found.

Strengths of study: This was a community-based, prospective cohort study with more than 23,000 person-years of follow up. More than 98% of the ACT cohort were seen at least once by eye care clinicians, with an average of 27 encounters. Dementia diagnoses were made by a panel of experts using research criteria. The possibility of healthy patient bias and potential confounders were thoroughly investigated.

Limitations of study: Results could be explained by unmeasured or residual confounding factors, like any observational study. There could be coding errors for cataract diagnosis. Only the participant's first cataract surgery was evaluated so researchers don't know whether subsequent surgeries impacted dementia risk. The majority of the study population was White, and it is unclear if the effect would be observed in all populations.

"Innovative research like Dr. Lee's is helping to uncover how age-related changes in our senses contribute to dementia," said Dr. Howard Fillit, founding executive director and chief science officer of the Alzheimer's Drug Discovery Foundation (ADDF), a nonprofit dedicated solely to accelerate the discovery and development of drugs to treat and prevent Alzheimer's disease and related dementias.

https://www.sciencedaily.com/releases/2021/12/211206113004.htm

Elevated heart rate linked to increased risk of dementia

December 3, 2021

Science Daily/Karolinska Institutet

Having an elevated resting heart rate in old age may be an independent risk factor of dementia, according to a study at Karolinska Institutet in Sweden published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Since resting heart rate is easy to measure and can be lowered through exercise or medical treatment, the researchers believe that it may help to identify people with higher dementia risk for early intervention.

The number of people living with dementia is expected to increase to 139 million globally by 2050, from 55 million in 2020, according to the organisation Alzheimer's Disease International. Currently, there is no cure for dementia, but growing evidence suggests that maintaining a healthy lifestyle and cardiovascular health could help delay the onset of dementia and ease symptoms.

In this study, the researchers examined if resting heart rate in 2,147 individuals 60 years old or older and living in Stockholm could be linked to dementia and cognitive decline independent of other known risk factors, such as cardiovascular disease.

The study, which followed the participants for up to 12 years, showed that individuals with a resting heart rate of 80 beats per minute or higher on average had 55 percent higher risk of dementia than those with a heart rate of 60-69 beats per minute. The association remained significant after adjusting for potential confounders such as various cardiovascular diseases. Still, the researchers caution that the result may have been affected by undetected cardiovascular events and the fact that more participants with cardiovascular disease died during the follow-up period and thus didn't have time to develop dementia.

The study cannot establish a causal relationship, but the researchers offer several plausible explanations for the association, including the effect of underlying cardiovascular diseases and cardiovascular risk factors, stiffened arteries, and imbalance between sympathetic and parasympathetic nerve activities.

"We believe it would be valuable to explore if resting heart rate could identify patients with high dementia risk," says the study's leading author Yume Imahori, a researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. "If we follow such patients' cognitive function carefully and intervene early, the onset of dementia might be delayed, which can have a substantial impact on their quality of life."

The study was led by senior lecturer Dr Chengxuan Qiu and the data was derived from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K).

The research was funded by the Swedish Ministry of Health and Social Affairs, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Foundation for International Cooperation in Research and Higher Education, Karolinska Institutet and the European Union.

https://www.sciencedaily.com/releases/2021/12/211203081519.htm

Potential new treatment for Alzheimer’s disease would be relatively cheap

November 30, 2021

Science Daily/RIKEN

Researchers at the RIKEN Center for Brain Science (CBS) in Japan have discovered that the protein α-endosulfine (ENSA) is involved in the development of Alzheimer's disease. Studies in mice showed that eliminating this protein entirely or using drugs to block its function reduced physical changes in the brain associated with the disease and improved memory. Drug therapy that aims to block ENSA activity could be a more effective treatment than what is currently available, as well as being cheaper. This study was published in the scientific journal Molecular Psychiatry.

The hallmark of Alzheimer's disease in the brain is the accumulation of amyloid β peptide (Aβ). For years, researchers have been trying to determine how and why this happens. Takaomi Saido and his team at RIKEN CBS have developed a mouse model of the disease that shows both Aβ accumulation and memory deficits similar to what is seen in humans. Using this model mouse, they have already discovered a series of events in the brain that lead to the formation of Aβ plaques. Key among them is reduced levels of the enzyme neprilysin, which itself is caused by reduced levels of the hormone somatostatin. Levels of both neprilysin and somatostatin go down as we age, which can explain why Alzheimer's disease usually strikes older people.

The new study focused on treating Alzheimer's disease in mice by figuring out how somatostatin controls neprilysin levels in the brain. According to first author Naoto Watamura, "the first step in this process was actually the most difficult because we had to develop an in vitro system that could screen for neprilsyin regulators in conditioned medium generated by hippocampal neurons." Once they accomplished this, they were able to identify ENSA as the regulator. Testing showed that ENSA reduced neprilysin activity and that it rose to abnormally high levels in the brains of mice that lacked somatostatin. This means that somatostatin normally keeps ENSA in check, which in turn keeps neprilsyin levels high, allowing Aβ to be destroyed before it accumulates.

Next the team focused on ENSA in living animals. Using CRISPR technology, they created ENSA knockout mice and then bred them with the Alzheimer's disease model mice. Aβ accumulation in these new mice was much lower than in the original model mice, indicating that abnormally high levels of ENSA could be an as yet unidentified symptom or biomarker of Alzheimer's disease. This was confirmed when the researchers detected high level of ENSA in the model mice and in the brains of people with Alzheimer's disease.

What exactly is ENSA doing in the brain? Tests showed that ENSA blocks a potassium channel in the hippocampus, a part of the brain needed for making and recalling memories. "Because we got the same results from blocking the KATP channel as we did from the ENSA knockout mice," says Watamura, "we reasoned that helping the channel stay open would combat the excess ENSA that we observed in Alzheimer's disease." To test this theory, the researchers fed the model mice with diazoxide -- a drug that activates the KATP channel -- and tested their memory. They found that while the untreated Alzheimer's disease model mice exhibited their characteristically poor memory, the treated model mice performed just as well as normal mice. A look at the brains of the treated mice showed that they lacked the hallmark Aβ plaques.

"Our findings point directly to a potential way of preventing and treating Alzheimer's disease," says Watamura. "On top of that, compared with Aβ-targeting immunotherapy, such as the drug aducanumab, which was recently approved by the FDA, synthetic agonists for the KATP channel are less expensive and would be more acceptable to aging societies around the world."

https://www.sciencedaily.com/releases/2021/11/211130101245.htm

Latte lovers rejoice! Drinking coffee could lower the risk of Alzheimer’s disease

Good news for those of us who can’t face the day without their morning flat white: a long-term study has revealed drinking higher amounts of coffee may make you less likely to develop Alzheimer’s disease

November 23, 2021

Science Daily/Edith Cowan University

Good news for those of us who can't face the day without their morning flat white: a long-term study has revealed drinking higher amounts of coffee may make you less likely to develop Alzheimer's disease.

As part of the Australian Imaging, Biomarkers and Lifestyle Study of ageing, researchers from Edith Cowan University (ECU) investigated whether coffee intake affected the rate of cognitive decline of more than 200 Australians over a decade.

Lead investigator Dr Samantha Gardener said results showed an association between coffee and several important markers related to Alzheimer's disease.

"We found participants with no memory impairments and with higher coffee consumption at the start of the study had lower risk of transitioning to mild cognitive impairment -- which often precedes Alzheimer's disease -- or developing Alzheimer's disease over the course of the study," she said.

Drinking more coffee gave positive results in relation to certain domains of cognitive function, specifically executive function which includes planning, self-control, and attention.

Higher coffee intake also seemed to be linked to slowing the accumulation of the amyloid protein in the brain, a key factor in the development of Alzheimer's disease.

Dr Gardener said although further research was needed, the study was encouraging as it indicated drinking coffee could be an easy way to help delay the onset of Alzheimer's disease.

"It's a simple thing that people can change," she said.

"It could be particularly useful for people who are at risk of cognitive decline but haven't developed any symptoms.

"We might be able to develop some clear guidelines people can follow in middle age and hopefully it could then have a lasting effect."

Make it a double

If you only allow yourself one cup of coffee a day, the study indicates you might be better off treating yourself to an extra cup, although a maximum number of cups per day that provided a beneficial effect was not able to be established from the current study.

"If the average cup of coffee made at home is 240g, increasing to two cups a day could potentially lower cognitive decline by eight per cent after 18 months," Dr Gardener said.

"It could also see a five per cent decrease in amyloid accumulation in the brain over the same time period."

In Alzheimer's disease, the amyloid clumps together forming plaques which are toxic to the brain.

The study was unable to differentiate between caffeinated and de-caffeinated coffee, nor the benefits or consequences of how it was prepared (brewing method, the presence of milk and/or sugar etc).

Dr Gardener said the relationship between coffee and brain function was worth pursuing.

"We need to evaluate whether coffee intake could one day be recommended as a lifestyle factor aimed at delaying the onset of Alzheimer's disease," she said.

More than just caffeine

Researchers are yet to determine precisely which constituents of coffee are behind its seemingly positive effects on brain health.

Though caffeine has been linked to the results, preliminary research shows it may not be the sole contributor to potentially delaying Alzheimer's disease.

"Crude caffeine" is the by-product of de-caffeinating coffee and has been shown to be as effective in partially preventing memory impairment in mice, while other coffee components such as cafestol, kahweol and Eicosanoyl-5-hydroxytryptamide have also been seen to affect cognitive impairment in animals in various studies.

'Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral A?-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study' was published in Frontiers of Ageing Neuroscience.

https://www.sciencedaily.com/releases/2021/11/211123131427.htm

Coffee and tea drinking may be associated with reduced rates of stroke and dementia

Intake of 4-6 total cups daily was associated with lowest risks

November 16, 2021

Science Daily/PLOS

Drinking coffee or tea may be associated with a lower risk of stroke and dementia, according to a study of healthy individuals aged 50-74 publishing Nov. 16 in the open-access journal PLOS Medicine. Drinking coffee was also associated with a lower risk of post-stroke dementia.

Strokes are life-threatening events which cause 10 percent of deaths globally. Dementia is a general term for symptoms related to decline in brain function and is a global health concern with a high economic and social burden. Post-stroke dementia is a condition where symptoms of dementia occur after a stroke.

Yuan Zhang and colleagues from Tianjin Medical University, Tianjin, China studied 365,682 participants from the UK Biobank, who were recruited between 2006 and 2010 and followed them until 2020. At the outset participants self-reported their coffee and tea intake. Over the study period, 5,079 participants developed dementia and 10,053 experienced at least one stroke.

People who drank 2-3 cups of coffee or 3-5 cups of tea per day, or a combination of 4-6 cups of coffee and tea had the lowest incidence of stroke or dementia. Individuals who drank 2-3 cups of coffee and 2-3 cups of tea daily had a 32% lower risk of stroke (HR, 0.68, 95% CI, 0.59-0.79; P <0.001) and a 28% lower risk of dementia (HR, 0.72, 95% CI, 0.59-0.89; P =0.002) compared with those who drank neither coffee nor tea. Intake of coffee alone or in combination with tea was also associated with lower risk of post-stroke dementia.

The UK Biobank reflects a relatively healthy sample relative to the general population which could restrict the ability to generalize these associations. Also, relatively few people developed dementia or stroke which can make it difficult to extrapolate rates accurately to larger populations. Finally, while it's possible that coffee and tea consumption might be protective against stroke, dementia and post-stroke dementia, this causality cannot be inferred from the associations.

The authors add, "Our findings suggested that moderate consumption of coffee and tea separately or in combination were associated with lower risk of stroke and dementia."

https://www.sciencedaily.com/releases/2021/11/211116144813.htm

Listening to favorite music improves brain plasticity

November 9, 2021

Science Daily/University of Toronto

Researchers at the University of Toronto (U of T) and Unity Health Toronto have demonstrated that repeated listening to personally meaningful music induces beneficial brain plasticity in patients with mild cognitive impairment or early Alzheimer's disease.

Changes in the brain's neural pathways correlated with increased memory performance on neuropsychological tests, supporting the clinical potential of personalized, music-based interventions for people with dementia.

The landmark multi-modal study was published today in the Journal of Alzheimer's Disease.

"We have new brain-based evidence that autobiographically salient music -- that is, music that holds special meaning for a person, like the song they danced to at their wedding -- stimulates neural connectivity in ways that help maintain higher levels of functioning," says Dr. Michael Thaut, senior author of the study, director of the Music and Health Science Research Collaboratory, Tier One Canada Research Chair in Music, Neuroscience and Health, and professor at U of T's Faculty of Music and Temerty Faculty of Medicine.

"Typically, it's very difficult to show positive brain changes in Alzheimer's patients. These preliminary yet encouraging results show improvement in the integrity of the brain, opening the door to further research on therapeutic applications of music for people with dementia -- musicians and non-musicians alike."

The research team reported structural and functional changes in neural pathways of study participants, notably in the prefrontal cortex, the brain's control centre where deep cognitive processes occur. Researchers showed that exposing the brains of patients with early-stage cognitive decline to autobiographically salient music activated a distinct neural network -- a musical network -- comprised of diverse brain regions that showed differences in activation after a period of daily music listening. Differences were also observed in the brain's connections and white matter, providing further evidence of neuroplasticity.

"Music-based interventions may be a feasible, cost-effective and readily accessible intervention for those in early-stage cognitive decline," says Dr. Corinne Fischer, lead author, director of Geriatric Psychiatry at St. Michael's Hospital of Unity Health Toronto and associate professor at U of T's Temerty Faculty of Medicine.

"Existing treatments for Alzheimer's disease have shown limited benefit to date. While larger controlled studies are required to confirm clinical benefits, our findings show that an individualized and home-based approach to music-listening may be beneficial and have lasting effects on the brain."

For the study, 14 participants -- eight non-musicians and six musicians -- listened to a curated playlist of autobiographically relevant, long-known music for one hour a day over the course of three weeks. Participants underwent structural and task-based functional MRI before and after the listening period to determine changes to brain function and structure. During these scans, they listened to clips of both long-known and newly composed music. Heard one hour before scanning, the new music was similar in style yet held no personal meaning.

When participants listened to the recently heard, newly composed music, brain activity occurred mainly in the auditory cortex, centered on the listening experience. However, when participants listened to long-known music, there was significant activation in the deep-encoded network of the prefrontal cortex, a clear indication of executive cognitive engagement. There was also strong engagement in subcortical brain regions, older areas minimally affected by Alzheimer's disease pathology.

The researchers reported subtle but distinct differences in structural and functional brain changes associated with music listening in musicians relative to non-musicians, though further studies in larger samples are needed to verify these findings. Repeated exposure to music with autobiographical salience improved cognition in all participants, regardless of musicianship.

"Whether you're a lifelong musician or have never even played an instrument, music is an access key to your memory, your pre-frontal cortex," says Thaut.

"It's simple -- keep listening to the music that you've loved all your life. Your all-time favourite songs, those pieces that are especially meaningful to you -- make that your brain gym."

This paper builds on a previous study in the same participant group that first identified the brain mechanisms that encode and preserve musical memories in people with early-stage cognitive decline.

Next, the researchers plan to replicate the study in a larger sample and institute a strong control condition to investigate the role of musicianship in moderating brain responses, and whether it is the music or the autobiographical content that induces changes in plasticity.

https://www.sciencedaily.com/releases/2021/11/211109120324.htm

Diagnosis of Alzheimer’s and related dementias reduces social activity

November 9, 2021

Science Daily/Rutgers University

Despite the belief that early diagnosis of Alzheimer's disease and other dementias is crucial, a new Rutgers study found that the diagnosis may unintentionally impact social relationships and activity.

The study, published in the journal Dementia and Geriatric Cognitive Disorders, examined how receiving a recent diagnosis of Alzheimer's disease and related dementias impacts social networks, social engagement and social support.

"Alzheimer's disease and related dementias are a public health priority that has a significant impact on people with these diseases, their families and society," said lead author Takashi Amano, an assistant professor in the Department of Social Work at Rutgers University-Newark. "In recent years, health professionals have wanted to diagnose people earlier because of benefits like better long-term care planning and less anxiety. While there are benefits to receiving an earlier diagnosis, negative consequences may include an increased risk of suicide or requesting physician-assisted suicide."

The study found that a person's social network and social support do not increase following a diagnosis of Alzheimer's and related dementias, which may be especially problematic for disadvantaged populations who have fewer resources.

According to the study -- which found that such a diagnosis reduces time talking on the phone, face-to-face contact and attending sports and other social events -- more than 6 million people in the United States were diagnosed with Alzheimer's disease and related dementias in 2020.

The researchers used data from the Health and Retirement Study, a national study that surveys adults and their spouses age 51 and older. Researchers tracked adults in 2012, 2014 and 2016.

Those who received a diagnosis in 2014 were compared to those who did not. The researchers measured their social relationships two years after their diagnosis, looking at social and informal engagement, such as meeting and talking on the phone, and formal engagement, like volunteering, attending educational programs, sports games or social events with clubs or non-religious organizations. Social network included the number of close ties a person had. Social support was perceived as either positive or negative.

The findings indicate that receiving a diagnosis of Alzheimer's disease and related dementias may have unintended impacts on social relationships, including decreased formal and informal social engagement.

Researchers suggest that practitioners and policymakers be aware of the consequences, identify strategies to alleviate the negative impact of receiving a diagnosis and look for ways to mobilize support networks after a diagnosis.

"Social relationships are an essential feature of our quality of life and can buffer against cognitive decline," said coauthor Addam Reynolds, a doctoral candidate at the Rutgers School of Social Work-New Brunswick. "Given the lack of a cure of these diseases, we must focus on ways people can maintain or improve their quality of life after receiving a diagnosis of Alzheimer's disease and related dementias."

Researchers say it may be especially important to promote informal social engagement -- face-to-face and telephone contact -- which is more accessible than formal social engagement.

https://www.sciencedaily.com/releases/2021/11/211109095336.htm

For women, greater exposure to estrogen in life may protect brain regions that are vulnerable to Alzheimer’s

November 4, 2021

Science Daily/Weill Cornell Medicine

The drop in estrogen levels that occurs with menopause brings declines in the volumes of "gray matter," the cellular matter of the brain, in key brain regions that are also affected in Alzheimer's disease. But a new study from Weill Cornell Medicine researchers, in collaboration with the University of Arizona, suggests that greater cumulative exposure to estrogen in life, for example from having had more children or from having taken menopause hormone therapy, may counter this brain-shrinking effect.

The findings, reported Nov. 3 in Neurology, come from an analysis of personal histories, MRI scans and cognitive tests on 99 women in their late 40s to late 50s. The researchers confirmed an earlier finding linking menopause to lower gray matter volume (GMV) in brain areas that are also vulnerable to Alzheimer's. But they also linked indicators of higher overall estrogen exposure, such as a longer span of reproductive years (menarche to menopause), more children and the use of menopause hormone therapy and hormonal contraceptives, to higher GMV in some of these brain areas.

The study was an observational study rather than a clinical trial, but it adds to the evidence that estrogen may have a protective effect on the female brain, limiting the loss of gray matter that normally comes with menopause, and thereby potentially reducing Alzheimer's risk.

"Our findings suggest that while the menopause transition may bring vulnerability for the female brain, other reproductive history events indicating greater estrogen exposure bring resilience instead," said study senior author Dr. Lisa Mosconi, an associate professor of neuroscience in neurology at Weill Cornell Medicine and director of the Women's Brain Initiative, and associate director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

Researchers estimate that nearly two thirds of those living with Alzheimer's in the United States are women. The higher prevalence of Alzheimer's in women may be due in part to women's greater longevity, among other reasons. A leading hypothesis is that that vulnerability relates to estrogen.

Receptors for estrogen molecules are found in cells throughout women's brains, and the sex hormone has long been known not just to help steer brain development and behavior but also generally to have a nourishing and protecting role in the central nervous system. That protection doesn't last forever, though. Estrogen levels decline steeply during the transition through menopause, and as recent research from Dr. Mosconi and others has shown, women tend to experience significant GMV loss during this transition.

The volume loss occurs especially in brain regions that are the most heavily affected in Alzheimer's, and at roughly the same time of life when the long, slow process of late-onset Alzheimer's is believed to start. Thus, women's mid-life loss of estrogen may be a key factor behind the higher risk of Alzheimer's.

The flip side of this hypothesis is that more estrogen, in particular a cumulatively greater estrogen exposure, could serve as a counter to the brain-weakening effect of menopause. That possibility is what Dr. Mosconi and her team sought to investigate in the new study.

The analysis covered 99 women aged 46-58 and a comparison group of 29 similarly aged men. It confirmed that the post-menopausal and peri-menopausal (starting menopause) women, compared with the pre-menopausal women and the men, had significantly lower GMV -- adjusted for age and head size -- in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions, which are heavily affected by Alzheimer's.

By contrast, among the women, having more estrogen exposure as implied by various factors was associated with greater GMV in certain brain areas. Longer reproductive span, for example, was significantly linked to more GMV in a cluster of regions near the top of the brain including the superior parietal lobule and precuneus of the left hemisphere. Having had more children was significantly associated with more GMV in inferior and middle frontal gyri, and middle and inferior temporal gyri. Having used hormone replacement therapy was associated with more GMV in superior frontal gyrus and several other brain regions. All these brain regions are known to be affected by aging and Alzheimer's.

The results support the idea that estrogen can be protective, the researchers say, and suggest that further investigation of the specific biological pathways underlying this effect could yield medical or lifestyle changes that help women reduce their risk of cognitive decline with aging as well as Alzheimer's dementia risk.

"We're hoping now to get further into the details of these links between estrogen and GMV, for example by comparing the effects of surgical menopause and spontaneous menopause, and by focusing specifically on certain types of estrogen exposure, such as menopause hormone therapy," said study first author Eva Schelbaum, research assistant in Dr. Mosconi's laboratory. "The goal as always is to understand why Alzheimer's affects more women than men, and how we can reduce that risk.

https://www.sciencedaily.com/releases/2021/11/211104140355.htm

Restoring normal sleep reduces amyloid-beta accumulation in mouse model of Alzheimer’s disease

November 3, 2021

Science Daily/Baylor College of Medicine

Multiple studies in humans and mouse models indicate that sleep disruptions raise the risk of Alzheimer's disease (AD) by increasing the accumulation of disease-relevant proteins such as amyloid-beta (A-beta) in the brain. In the current study, a team led by researchers at Baylor College of Medicine discovered that, in an animal model of Alzheimer's disease, restoring normal sleep by returning to normal the activity of the thalamic reticular nucleus (TRN), a brain region involved in maintaining stable sleep, reduced the accumulation of A-beta plaques in the brain.

Published in the journal Science Translational Medicine, the study suggests that TRN not only may play a previously unsuspected driving role in symptoms associated with Alzheimer's, but also that restoring its normal activity could be a potential therapeutic approach for this severe condition.

The TRN is quiet in AD

"Our interest in studying the TRN in the context of Alzheimer's disease began when we observed in an animal model that TRN activity was generally reduced when compared to the TRN activity of animals without the condition," said corresponding author Dr. Jeannie Chin, associate professor of neuroscience at Baylor.

When we sleep, the TRN is in general more active than when we are awake, Chin explained. This increased TRN activity reduces the perception of peripheral sensory information. Consequently, when we sleep, we typically are not aware of sounds, lights and other sensations, which helps us get a good night sleep.

"Observing that the TRN in our animal model was less active than in animals without the condition, we investigated the possibility that a quiet TRN could be a reason for the sleep interruptions that are common in people with Alzheimer's disease," said first author Dr. Rohan Jagirdar, an instructor in the Chin lab.

The researchers began by determining whether their Alzheimer's disease mice would wake up more often than mice without the disease during normal sleeping hours. Using a wireless system to record the animals' brain activity, the researchers discovered that, indeed, the Alzheimer's mice woke up 50% more times than non-Alzheimer's mice. Moreover, the Alzheimer's mice got less than the normal amount of slow wave sleep, the deep restorative sleep during which waste products and metabolites are cleared from the brain. This was observed in the early stages of disease progression, before the animals developed memory deficits.

"This finding is relevant to the human condition, as research has shown that sleep fragmentation and other sleep disturbances in cognitively normal people are associated with increased Alzheimer's disease risk," Chin said. "When AD mice got older, reaching about three to five months, their sleep continued to be disrupted and they also presented with memory deficits."

Quiet TRN linked to A-beta plaque load

In the AD animal model, measurable levels of A-beta began to appear in the brain when the mice reached about one month of age and began to deposit into plaques by approximately six months of age.

"We assessed whether the sleep fragmentation and reduction of slow wave sleep that we observed in our AD mouse model might be associated with the accumulation of A-beta at later stages, by examining mice at six to seven months of age," Jagirdar said. "We found that the magnitude of sleep fragmentation was directly related to plaque load in the brains of six-month-old AD mice."

Taken together, these findings show that AD mice present disruptions in sleep that could influence the accumulation of proteins involved in disease progression.

In addition, Chin, Jagirdar and their colleagues analyzed postmortem tissues from patients who had either Alzheimer's disease, mild cognitive impairment or none of those conditions. They discovered that, as they had found in the mouse model, neurons in the TRN of Alzheimer's patients showed signs of having been less active when compared to the controls. Also, the brains of AD patients with the least active TRN had the highest A-beta plaque deposition. These findings support the possibility of a relationship between reduced TRN activity and increased accumulation of disease-causing proteins in AD.

Could reactivating TRN improve the condition?

Using a chemogenetic system, a technology that allows one to chemically activate specific cells, the team activated TRN neurons in the animal model. After a single round of chemogenetic activation of the TRN, the AD-mice woke up less often and spent more time in slow wave sleep, signs of improved sleep activity.

"It was exciting to see that, after receiving chemogenetic activation of the TRN daily for a month, the AD mice showed sustained activation of TRN neurons, consistent improvements in sleep and, remarkably, reduced accumulation of A-beta," Chin said.

The researchers point out that, although this approach seems to improve sleep disruption and A-beta deposition in this mouse model of Alzheimer's disease, not all sleep disturbances involve TRN.

"Sleep disturbances are associated with a number of disorders and arise from diverse causes," Jagirdar explained. "Targeting the TRN may not be as effective if the sleep disturbance is due to unrelated causes, such as obstructive sleep apnea or restless leg syndrome."

"Our findings support that selective activation of the TRN is a promising therapeutic intervention to improve sleep disturbances and slow the accumulation of A-beta in AD," Chin said.

https://www.sciencedaily.com/releases/2021/11/211103150856.htm

Four commonly used medications reverse Alzheimer's disease in mice

October 27, 2021

Science Daily/Institute for Research in Biomedicine (IRB Barcelona)

Alzheimer's disease is the most common cause of dementia in Western societies and it is estimated that 24 million people worldwide have this condition. ICREA researcher Dr. Patrick Aloy, head of the Structural Bioinformatics and Network Biology lab at IRB Barcelona, has headed a study that has managed to reverse the symptoms of Alzheimer's disease in mice by administering drugs currently used to treat hypertension and inflammation in humans.

In this study, the scientists led by Dr. Aloy have characterised three stages of Alzheimer's disease, namely initial, intermediate and advanced. For each of these stages, they have analysed the behaviour of the animals, studied the effects on the brain (specifically the hippocampus at the tissue level) and performed a molecular analysis to measure gene expression and protein levels.

The approach adopted has allowed them to describe the development of the disease at a level of detail hitherto unknown and also compare it with healthy ageing. "What we have observed is that, although Alzheimer's disease shares some features of accelerated ageing, it is also affected by totally different ageing processes," says Dr. Aloy. "This disease is caused by the abnormal accumulation of certain proteins, and we have seen that, in some cases, this is not caused by overproduction but by an error in their removal," he adds.

Chemical Checker: detection of the most promising molecules

Having characterised the disease, the scientists used the Chemical Checker, a computational tool developed by the same research group to find drugs already on the market with the capacity to reverse the effects at the cellular level. This tool has allowed them to identify a series of possible candidates, which were tested in various mouse models of Alzheimer's disease. Four drugs -- two non-steroidal anti-inflammatories and two anti-hypertensives, proved effective at reversing the disease and neutralising symptoms in these mice.

"Epidemiological studies already indicated that people who regularly take antiinflammatories show a lower incidence of Alzheimer's disease, but this had not been correlated with a specific medication or mechanism. The results that we are publishing are most promising, and we hope that further research can be done on them because they could give rise to a paradigm shift in the treatment of this disease," says Dr. Aloy.

Early diagnosis of the disease

In addition to paving new avenues of research for the treatment of Alzheimer's disease, the characterisation of the distinct stages of this condition published in this study favours early diagnosis. Diagnosing Alzheimer's disease at an early stage, when damage to the brain is still minimal, is one of the main research focuses to tackle this condition and to reduce symptoms.

This work has been done in collaboration with the RIKEN Center for Brain Science and the Institute of Brain Science, both in Japan, and the Biostatistics/Bioinformatics and also Proteomics core facility at IRB Barcelona. The study was funded by the European Research Council, the Spanish Ministry of Science and Innovation and the Government of Catalonia.

https://www.sciencedaily.com/releases/2021/10/211027122112.htm

Why do we remember stressful experiences better?

October 15, 2021

Science Daily/Ruhr-University Bochum

Stressful experiences are usually remembered more easily than neutral experiences. Researchers at Ruhr-Universität Bochum (RUB) have analysed the reasons why this is the case. They put people in stressful situations during simulated job interviews and then recorded their memory of objects from these interviews. Using functional magnetic resonance imaging, they analysed brain activity while the participants saw the objects again. Memories of objects from stressful situations seem to rely on similar brain activity as memories of the stress trigger itself.

The team headed by Anne Bierbrauer, Professor Oliver Wolf and Professor Nikolai Axmacher from the RUB Institute of Cognitive Neuroscience describes the findings in the journal Current Biology, published online on 14 October 2021.

Different theories

"We usually have detailed images in your mind's eye of stressful experiences, such as taking the driving test, even after many years," says Oliver Wolf. "Whereas a walk through the park on the same day is quickly forgotten." The neuroscientists at RUB would like to understand the reasons for this phenomenon.

Earlier studies and theoretical considerations had led to different predictions about how memories of stressful experiences differ from neutral ones: "One idea was that very different memory representations might have been the key to more powerful memories; on the other hand, there were indications that stress memories have resembled each other more closely," explains Anne Bierbrauer. The current study provides evidence for the second theory.

Analysing stressful experiences in the lab

Unlike in many laboratory studies, the researchers set out to record the memory trace of a real event in their experiments, using the so-called Trier Social Stress Test for this purpose. This test requires the participants to speak in front of an application committee, all of whom wear a neutral expression and don't give any positive feedback. The test unfailingly triggers stress in the participants.

During the job interview simulation, the committee used a number of everyday objects; for example, one of the committee members took a sip from a coffee cup. The control group was confronted with the same objects, but the participants were not subjected to any stress. One day later, the researchers showed the objects to participants in both groups while recording brain activity in a magnetic resonance imaging scanner. The stressed participants remembered the objects better than members of the control group.

The researchers analysed primarily the brain activity in the amygdala, a region whose main functions include emotional learning. They compared the neuronal traces of objects that had been used by the committee members in the stress situation with those of objects that hadn't been used. The result was: the memory traces of objects that had been used resembled each other more closely than those of objects that hadn't been used. This was not the case in the control group. In other words, the brain representations of the objects from the stressful situations were very closely linked, and they were thus clearly set apart from other experiences.

Stressful memories are based on their resemblance to the stressor

One day after the stress test, the researchers showed the participants not only pictures of the objects from the job interview, but also photos of members of the committee. The participants mainly remembered objects where the brain activity was similar to the activity triggered by the presentation of the committee members. "The committee members triggered the stress in the interview situation. Accordingly, it seems that the link between the objects and the stress triggers was crucial for the enhanced memory," concludes Nikolai Axmacher.

The findings obtained in this study argue against the theory that stronger memories are triggered by memory representations that differ from each other as much as possible -- at least when it comes to emotional or stressful memories. Rather, the mechanism that reinforces emotional memories appears to be rooted in the fact that the important aspects of the episode are linked at the neural level and become more closely related to the stress trigger. "This result could be an important building block to better understand emotional and traumatic memories," points out Anne Bierbrauer.

https://www.sciencedaily.com/releases/2021/10/211015184209.htm

Optimal blood pressure helps our brains age slower

Optimal blood pressure helps our brains stay at least six months younger than our actual age

October 12, 2021

Science Daily/Australian National University

People with elevated blood pressure that falls within the normal recommended range are at risk of accelerated brain ageing, according to new research from The Australian National University (ANU).

The research also found optimal blood pressure helps our brains stay at least six months younger than our actual age. The researchers are now calling for national health guidelines to be updated to reflect their important findings.

The ANU study, published in Frontiers in Aging Neuroscience, found participants with high blood pressure had older and therefore less healthy brains, increasing their risk of heart disease, stroke and dementia.

Participants with an elevated blood pressure, but within the normal range, also had older looking brains and were at risk of health problems.

"This thinking that one's brain becomes unhealthy because of high blood pressure later in life is not completely true," Professor Nicolas Cherbuin, Head of the ANU Centre for Research on Ageing, Health and Wellbeing, said.

"It starts earlier and it starts in people who have normal blood pressure."

Normal blood pressure is defined by pressure below 120/80, whereas an optimal and healthier blood pressure is closer to 110/70.

The new research comes after a large international study found the number of people over 30 with high blood pressure has doubled globally.

Cardiologist and co-author of the study, Professor Walter Abhayaratna, said if we maintain optimal blood pressure our brains will remain younger and healthier as we age.

"It's important we introduce lifestyle and diet changes early on in life to prevent our blood pressure from rising too much, rather than waiting for it to become a problem," he said.

"Compared to a person with a high blood pressure of 135/85, someone with an optimal reading of 110/70 was found to have a brain age that appears more than six months younger by the time they reach middle age."

The ANU team, in collaboration with colleagues in Australia, New Zealand and Germany, examined more than 2,000 brain scans of 686 healthy individuals aged 44 to 76.

The blood pressure of the participants was measured up to four times across a 12-year period. The brain scan and blood pressure data was used to determine a person's brain age, which is a measure of brain health.

Lead author, Professor Cherbuin, said the findings highlight a particular concern for young people aged in their 20s and 30s because it takes time for the effects of increased blood pressure to impact the brain.

"By detecting the impact of increased blood pressure on the brain health of people in their 40s and older, we have to assume the effects of elevated blood pressure must build up over many years and could start in their 20s. This means that a young person's brain is already vulnerable," he said.

Professor Abhayaratna said the research findings show the need for everyone, including young people, to check their blood pressure regularly.

"Australian adults should take the opportunity to check their blood pressure at least once a year when they see their GP, with an aim to ensure that their target blood pressure is closer to 110/70, particularly in younger and middle age groups," he said.

"If your blood pressure levels are elevated, you should take the opportunity to speak with your GP about ways to reduce your blood pressure, including the modification of lifestyle factors such as diet and physical activity."

https://www.sciencedaily.com/releases/2021/10/211012112239.htm

Clean air matters for a healthy brain

Research on air pollution and cognitive decline indicate cleaner air may reduce risk for Alzheimer’s and other dementias

October 7, 2021

Science Daily/University of Southern California

Two USC researchers whose work linked air pollution to a greater risk of Alzheimer's disease and faster cognitive decline are seeing signs that cleaner air can make a difference in brain health.

Cars and factories produce a fine particulate known as PM2.5 that USC-led studies have linked to memory loss and Alzheimer's disease. Smaller than the width of a human hair, these tiny particles pose a big problem. Once inhaled, they pass directly from the nose up and into the brain, beyond the blood-brain barrier that normally protects the brain from dust or other invaders.

In a research letter published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, the USC researchers described how their labs each independently reported indications of recent decreases in neurotoxicity (damage to the brain or nervous system caused by exposure to toxic substances) of PM2.5 air pollution in humans and mice.

University Professor Caleb Finch and associate professor of gerontology and sociology Jennifer Ailshire, both with the USC Leonard Davis School of Gerontology, focused on PM2.5 pollution. Long-term exposure to PM2.5 has been linked to premature death, particularly in people with chronic heart or lung diseases.

Ailshire's research, published earlier this year in the Journal of Alzheimer's Disease, showed a strong association between cognitive deficits and air pollution among people with lower levels of education in 2004.

Based on data from the nationwide Health and Retirement Study, her work showed that, when exposed to PM2.5, adults 65 and older who had fewer than eight years of education faced a greater risk of cognitive impairment. But one decade later, Ailshire found no such association for study participants.

A likely factor was the reduction in PM2.5 over the prior decade, said Ailshire. Air quality data showed the average annual PM2.5 levels in the study participants' neighborhoods were 25% below 2004 levels.

Notably in 2014, very few of the study participants lived in places with annual average PM2.5 that exceeded U.S. Environmental Protection Agency air quality standards. This further suggested that the improvements with cognitive decline were linked to a drop in exposure to high pollution among older adults.

"Improving air quality around the country has been a tremendous public health and environment policy success story. But there are signs of a reversal in these trends," Ailshire said. "Pollution levels are creeping up again and there are increasingly more large fires, which generate a significant amount of air pollution in certain parts of the country. This gives me cause for concern about future trends in improving air quality."

Finch's research on mice, published earlier this year in the Journal of Alzheimer's Disease, also found evidence of lower neurotoxicity of air pollution over time.

Finch and his research team have studied pollution levels at the same Los Angeles site and their effect on mouse brains since 2009. After 2017, the mice exposed to a tiny, nanoscale version of PM2.5 appeared healthier. Markedly, they showed sharp declines in several factors of neurotoxicity, including oxidative damage to cells and tissues.

During the years that Finch's and Ailshire's studies were taking place, the composition of air pollution in the United States was also changing.

From 2000 to 2020, PM2.5 levels declined nationwide by 41%, according to the EPA. In contrast, urban PM2.5 in Los Angeles declined only slightly from 2009 to 2019. While nationwide ozone levels decreased, Los Angeles County ozone reversed the prior trends by increasing after 2015.

Finch and Ailshire emphasize that their findings cannot evaluate potential benefits of air pollution improvements to the risk of cognitive decline and dementia. Although PM2.5 levels declined nationally from 2009 to 2016, the year-over-year increases that have been observed since 2017 show that improvements in air quality can be reversed, as they were in Los Angeles.

"Our findings underscore the importance of efforts to improve air quality as well as the continued importance of demographic and experimental evaluation of air pollution neurotoxicity," Finch said.

Finch and Jiu-Chiuan "J.C." Chen, an associate professor of preventive medicine at the Keck School of Medicine of USC, previously published a study using both human and animal data that showed brain aging processes worsened by air pollution may increase dementia risk. Their research indicated that older women who lived in locations with high levels of PM2.5 suffered memory loss and Alzheimer's-like brain shrinkage not seen in women living with cleaner air.

https://www.sciencedaily.com/releases/2021/10/211007122123.htm

Natural compound in basil may protect against Alzheimer’s disease pathology

October 5, 2021

Science Daily/University of South Florida (USF Health)

Fenchol, a natural compound abundant in some plants including basil, can help protect the brain against Alzheimer's disease pathology, a preclinical study led by University of South Florida Health (USF Health) researchers suggests.

The new study published Oct. 5 in the Frontiers in Aging Neuroscience (@FrontiersIn), discovered a sensing mechanism associated with the gut microbiome that explains how fenchol reduces neurotoxicity in the Alzheimer's brain.

Emerging evidence indicates that short-chain fatty acids (SCFAs)- metabolites produced by beneficial gut bacteria and the primary source of nutrition for cells in your colon -- contribute to brain health. The abundance of SCFAs is often reduced in older patients with mild cognitive impairment and Alzheimer's disease, the most common form of dementia. However, how this decline in SCFAs contributes to Alzheimer's disease progression remains largely unknown.

Gut-derived SCFAs that travel through the blood to the brain can bind to and activate free fatty acid receptor 2 (FFAR2), a cell signaling molecule expressed on brain cells called neurons.

"Our study is the first to discover that stimulation of the FFAR2 sensing mechanism by these microbial metabolites (SCFAs) can be beneficial in protecting brain cells against toxic accumulation of the amyloid-beta (Aβ) protein associated with Alzheimer's disease," said principal investigator Hariom Yadav, PhD, professor of neurosurgery and brain repair at the USF Health Morsani College of Medicine, where he directs the USF Center for Microbiome Research.

One of the two hallmark pathologies of Alzheimer's disease is hardened deposits of Aβ that clump together between nerve cells to form amyloid protein plaques in the brain. The other is neurofibrillary tangles of tau protein inside brain cells. These pathologies contribute to the neuron loss and death that ultimately cause the onset of Alzheimer's, a neurodegenerative disease characterized by loss of memory, thinking skills and other cognitive abilities.

Dr. Yadav and his collaborators delve into molecular mechanisms to explain how interactions between the gut microbiome and the brain might influence brain health and age-related cognitive decline. In this study, Dr. Yadav said, the research team set out to uncover the "previously unknown" function of FFAR2 in the brain.

The researchers first showed that inhibiting the FFAR2 receptor (thus blocking its ability to "sense" SCFAs in the environment outside the neuronal cell and transmit signaling inside the cell) contributes to the abnormal buildup of the Aβ protein causing neurotoxicity linked to Alzheimer's disease.

Then, they performed large-scale virtual screening of more than 144,000 natural compounds to find potential candidates that could mimic the same beneficial effect of microbiota produced SCFAs in activating FFAR2 signaling. Identifying a natural compound alternative to SCFAs to optimally target the FFAR2 receptor on neurons is important, because cells in the gut and other organs consume most of these microbial metabolites before they reach the brain through blood circulation, Dr. Yadav noted.

Dr. Yadav's team narrowed 15 leading compound candidates to the most potent one. Fenchol, a plant-derived compound that gives basil its aromatic scent, was best at binding to the FFAR's active site to stimulate its signaling.

Further experiments in human neuronal cell cultures, as well as Caenorhabditis (C.) elegans (worm) and mouse models of Alzheimer's disease demonstrated that fenchol significantly reduced excess Aβ accumulation and death of neurons by stimulating FFAR2 signaling, the microbiome sensing mechanism. When the researchers more closely examined how fenchol modulates Aβ-induced neurotoxicity, they found that the compound decreased senescent neuronal cells, also known as "zombie" cells, commonly found in brains with Alzheimer's disease pathology.

Zombie cells stop replicating and die a slow death. Meanwhile, Dr. Yadav said, they build up in diseased and aging organs, create a damaging inflammatory environment, and send stress or death signals to neighboring healthy cells, which eventually also change into harmful zombie cells or die.

"Fenchol actually affects the two related mechanisms of senescence and proteolysis," Dr. Yadav said of the intriguing preclinical study finding. "It reduces the formation of half-dead zombie neuronal cells and also increases the degradation of (nonfunctioning) Aβ, so that amyloid protein is cleared from the brain much faster."

Before you start throwing lots of extra basil in your spaghetti sauce or anything else you eat to help stave off dementia, more research is needed -- including in humans.

In exploring fenchol as a possible approach for treating or preventing Alzheimer's pathology, the USF Health team will seek answers to several questions. A key one is whether fenchol consumed in basil itself would be more or less bioactive (effective) than isolating and administering the compound in a pill, Dr. Yadav said. "We also want to know whether a potent dose of either basil or fenchol would be a quicker way to get the compound into the brain."

https://www.sciencedaily.com/releases/2021/10/211005101827.htm

Happiness in early adulthood may protect against dementia

Depressive symptoms increase risk for cognitive impairment

September 28, 2021

Science Daily/University of California - San Francisco

While research has shown that poor cardiovascular health can damage blood flow to the brain increasing the risk for dementia, a new study led by UC San Francisco indicates that poor mental health may also take its toll on cognition.

The research adds to a body of evidence that links depression with dementia, but while most studies have pointed to its association in later life, the UCSF study shows that depression in early adulthood may lead to lower cognition 10 years later and to cognitive decline in old age.

The study publishes in the Journal of Alzheimer's Disease on Sept. 28, 2021.

The researchers used innovative statistical methods to predict average trajectories of depressive symptoms for approximately 15,000 participants ages 20 to 89, divided into three life stages: older, midlife and young adulthood. They then applied these predicted trajectories and found that in a group of approximately 6,000 older participants, the odds of cognitive impairment were 73 percent higher for those estimated to have elevated depressive symptoms in early adulthood, and 43 percent higher for those estimated to have elevated depressive symptoms in later life.

These results were adjusted for depressive symptoms in other life stages and for differences in age, sex, race, educational attainment, body mass index, history of diabetes and smoking status. For depressive symptoms in midlife, the researchers found an association with cognitive impairment, but this was discounted when they adjusted for depression in other life stages.

Excess Stress Hormones May Damage Ability to Make New Memories

"Several mechanisms explain how depression might increase dementia risk," said first author Willa Brenowitz, PhD, MPH, of the UCSF Department of Psychiatry and Behavioral Sciences and the Weill Institute for Neurosciences. "Among them is that hyperactivity of the central stress response system increases production of the stress hormones glucocorticoids, leading to damage of the hippocampus, the part of the brain essential for forming, organizing and storing new memories."

Other studies have linked depression with atrophy of the hippocampus, and one study has shown faster rates of volume loss in women, she said.

In estimating the depressive symptoms across each life stage, researchers pooled data from younger participants with data from the approximately 6,000 older participants and predicted average trajectories. These participants, whose average age was 72 at the start of the study and lived at home, had been enrolled by the Health Aging and Body Composition Study and the Cardiovascular Health Study. They were followed annually or semi-annually for up to 11 years.

U-Shaped Curve Adds Credence to Predicted Trajectories 

While assumed values were used, the authors stated, no longitudinal studies have been completed across the life course. "Imputed depressive symptom trajectories fit a U-shaped curve, similar to age-related trends in other research," they noted.

Participants were screened for depression using a tool called the CESD-10, a 10-item questionnaire assessing symptoms in the past week. Moderate or high depressive symptoms were found in 13 percent of young adults, 26 percent of midlife adults and 34 percent of older participants.

Some 1,277 participants were diagnosed with cognitive impairment following neuropsychological testing, evidence of global decline, documented use of a dementia medication or hospitalization with dementia as a primary or secondary diagnosis.

"Generally, we found that the greater the depressive symptoms, the lower the cognition and the faster the rates of decline," said Brenowitz, who is also affiliated with the UCSF Department of Epidemiology and Biostatistics. "Older adults estimated to have moderate or high depressive symptoms in early adulthood were found to experience a drop in cognition over 10 years."

With up to 20 percent of the population suffering from depression during their lifetime, it's important to recognize its role in cognitive aging, said senior author Kristine Yaffe, MD, of the UCSF departments of Psychiatry and Behavioral Sciences, and Epidemiology and Biostatistics. "Future work will be needed to confirm these findings, but in the meantime, we should screen and treat depression for many reasons."

https://www.sciencedaily.com/releases/2021/09/210928121341.htm

MIND diet linked to better cognitive performance

Study finds diet may contribute to cognitive resilience in the elderly

September 21, 2021

Science Daily/Rush University Medical Center

Aging takes a toll on the body and on the mind. For example, the tissue of aging human brains sometimes develops abnormal clumps of proteins that are the hallmark of Alzheimer's disease. How can you protect your brain from these effects?

Researchers at Rush University Medical Center have found that older adults may benefit from a specific diet called the MIND diet even when they develop these protein deposits, known as amyloid plaques and tangles. Plaques and tangles are a pathology found in the brain that build up in between nerve cells and typically interfere with thinking and problem-solving skills.

Developed by the late Martha Clare Morris, ScD, who was a Rush nutritional epidemiologist, and her colleagues, the MIND diet is a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets. Previous research studies have found that the MIND diet may reduce a person's risk of developing Alzheimer's disease dementia.

Now a study has shown that participants in the study who followed the MIND diet moderately later in life did not have cognition problems, according to a paper published on Sept. 14 in the Journal of Alzheimer's Disease.

"Some people have enough plaques and tangles in their brains to have a postmortem diagnosis of Alzheimer's disease, but they do not develop clinical dementia in their lifetime," said Klodian Dhana, MD, PhD, lead author of the paper and an assistant professor in the Division of Geriatrics and Palliative Medicine in the Department of Internal Medicine at Rush Medical College .

"Some have the ability to maintain cognitive function despite the accumulation of these pathologies in the brain, and our study suggests that the MIND diet is associated with better cognitive functions independently of brain pathologies related to Alzheimer's disease.

In this study, the researchers examined the associations of diet -- from the start of the study until death -- brain pathologies and cognitive functioning in older adults who participated in the Rush Alzheimer's Disease Center's ongoing Memory and Aging Project, which began in 1997 and includes people living in greater Chicago. The participants were mostly white without known dementia, and all of them agreed to undergo annual clinical evaluations while alive and brain autopsy after their death.

The researchers followed 569 participants, who were asked to complete annual evaluations and cognitive tests to see if they had developed memory and thinking problems. Beginning in 2004, participants were given an annual food frequency questionnaire about how often they ate 144 food items in previous year.

Using the questionnaire answers, the researchers gave each participant a MIND diet score based on how often the participants ate specific foods. The MIND diet has 15 dietary components, including 10 "brain-healthy food groups" and five unhealthy groups -- red meat, butter and stick margarine, cheese, pastries and sweets, and fried or fast food.

To adhere to and benefit from the MIND diet, a person would need to eat at least three servings of whole grains, a green leafy vegetable and one other vegetable every day -- along with a glass of wine -- snack most days on nuts, have beans every other day or so, eat poultry and berries at least twice a week and fish at least once a week. A person also must limit intake of the designated unhealthy foods, limiting butter to less than 1 1/2 teaspoons a day and eating less than a serving a week of sweets and pastries, whole fat cheese, and fried or fast food.

Based on the frequency of intake reported for the healthy and unhealthy food groups, the researchers calculated the MIND diet score for each participant across the study period. An average of the MIND diet score from the start of the study until the participant's death was used in the analysis to limit measurement error. Seven sensitivity measures were calculated to confirm accuracy of the findings.

"We found that a higher MIND diet score was associated with better memory and thinking skills independently of Alzheimer's disease pathology and other common age-related brain pathologies. The diet seemed to have a protective capacity and may contribute to cognitive resilience in the elderly." Dhana said.

"Diet changes can impact cognitive functioning and risk of dementia, for better or worse," he continued. "There are fairly simple diet and lifestyle changes a person could make that may help to slow cognitive decline with aging, and contribute to brain health."

https://www.sciencedaily.com/releases/2021/09/210921172721.htm

Cholesterol drives Alzheimer’s plaque formation

September 14, 2021

Science Daily/University of Virginia Health System

Cholesterol manufactured in the brain appears to play a key role in the development of Alzheimer's disease, new research indicates.

Scientists from the University of Virginia School of Medicine and their collaborators found that cholesterol produced by cells called astrocytes is required for controlling the production of amyloid beta, a sticky protein that builds up in the brains of patients with Alzheimer's. The protein accumulates into insoluble plaques that are a hallmark of the disease. Many efforts have targeted these plaques in the hope that removing or preventing them could treat or prevent Alzheimer's.

The new findings offer important insights into how and why the plaques form and may explain why genes associated with cholesterol have been linked to increased risk for Alzheimer's. The results also provide scientists with important direction as they seek to prevent Alzheimer's.

"This study helps us to understand why genes linked to cholesterol are so important to the development of Alzheimer's disease," said researcher Heather A. Ferris, MD, PhD, of UVA's Division of Endocrinology and Metabolism. "Our data point to the importance of focusing on the production of cholesterol in astrocytes and the transport to neurons as a way to reduce amyloid beta and prevent plaques from ever being formed."

Alzheimer's Plaques and Cholesterol

While cholesterol is often associated with clogged arteries and heart disease, it plays important roles in the healthy body. The body makes cholesterol naturally so it can produce hormones and carry out other important functions. The new discovery from Ferris and her collaborators adds a new entry to cholesterol's list of responsibilities.

The work also sheds light on the role of astrocytes in Alzheimer's disease. Scientists have known that these common brain cells undergo dramatic changes in Alzheimer's, but they have been uncertain if the cells were suffering from the disease or contributing to it. The new results suggest the latter.

The scientists found that astrocytes help drive the progression of Alzheimer's by making and distributing cholesterol to brain cells called neurons. This cholesterol buildup increases amyloid beta production and, in turn, fuels plaque accumulation.

Normally, cholesterol is kept quite low in neurons, limiting the buildup of amyloid beta. But in Alzheimer's, the neurons lose their ability to regulate amyloid beta, resulting in plaque formation.

Blocking the astrocytes' cholesterol manufacturing "robustly" decreased amyloid beta production in lab mice, the researchers report in a new scientific paper. It's too soon to say if this could be mimicked in people to prevent plaque formation, but the researchers believe that further research is likely to yield important insights that will benefit the battle against Alzheimer's.

The fact that amyloid beta production is normally tightly controlled suggests that it may play an important role in brain cells, the researchers say. As such, doctors may need to be careful in trying to block or remove amyloid beta. Additional research into the discovery could shed light on how to prevent the over-production of amyloid beta as a strategy against Alzheimer's, the researchers believe.

"If we can find strategies to prevent astrocytes from over-producing cholesterol, we might make a real impact on the development of Alzheimer's disease," Ferris said. "Once people start having memory problems from Alzheimer's disease, countless neurons have already died. We hope that targeting cholesterol can prevent that death from ever occurring in the first place."

https://www.sciencedaily.com/releases/2021/09/210914100118.htm

Brain refreshing: Why the dreaming phase matters

August 25, 2021

Science Daily/University of Tsukuba

Researchers have found that blood flow in the brain capillaries, which is important for oxygen/nutrient delivery and waste removal, was increased during rapid eye movement sleep in mice. Adenosine A2a receptors might be at least partially responsible for this increased blood flow. These findings bring new hope for understanding the function of sleep and developing treatments for neurodegenerative diseases that involve the buildup of waste products in the brain, such as Alzheimer's disease.

Scientists have long wondered why almost all animals sleep, despite the disadvantages to survival of being unconscious. Now, researchers led by a team from the University of Tsukuba have found new evidence of brain refreshing that takes place during a specific phase of sleep: rapid eye movement (REM) sleep, which is when you tend to dream a lot.

Previous studies have measured differences in blood flow in the brain between REM sleep, non-REM sleep, and wakefulness using various methods, with conflicting results. In their latest work, the Tsukuba-led team used a technique to directly visualize the movement of red blood cells in the brain capillaries (where nutrients and waste products are exchanged between brain cells and blood) of mice during awake and asleep states.

"We used a dye to make the brain blood vessels visible under fluorescent light, using a technique known as two-photon microscopy," says senior author of the study Professor Yu Hayashi. "In this way, we could directly observe the red blood cells in capillaries of the neocortex in non-anesthetized mice."

The researchers also measured electrical activity in the brain to identify REM sleep, non-REM sleep, and wakefulness, and looked for differences in blood flow between these phases.

"We were surprised by the results," explains Professor Hayashi. "There was a massive flow of red blood cells through the brain capillaries during REM sleep, but no difference between non-REM sleep and the awake state, showing that REM sleep is a unique state"

The research team then disrupted the mice's sleep, resulting in "rebound" REM sleep -- a stronger form of REM sleep to compensate for the earlier disruption. Blood flow in the brain was further increased during rebound REM sleep, suggesting an association between blood flow and REM sleep strength. However, when the researchers repeated the same experiments in mice without adenosine A2a receptors (the receptors whose blockade makes you feel more awake after drinking coffee), there was less of an increase in blood flow during REM sleep, even during rebound REM sleep.

"These results suggest that adenosine A2a receptors may be responsible for at least some of the changes in blood flow in the brain during REM sleep," says Professor Hayashi.

Given that reduced blood flow in the brain and decreased REM sleep are correlated with the development of Alzheimer's disease, which involves the buildup of waste products in the brain, it may be interesting to address whether increased blood flow in the brain capillaries during REM sleep is important for waste removal from the brain. This study lays preliminary groundwork for future investigations into the role of adenosine A2a receptors in this process, which could ultimately lead to the development of new treatments for conditions such as Alzheimer's disease.

https://www.sciencedaily.com/releases/2021/08/210825113638.htm