Links between paranormal beliefs and cognitive function described by 40 years of research
New evaluation of prior studies finds increasing quality and areas for further improvement
May 4, 2022
Science Daily/PLOS
In a review of 71 studies that explored links between belief in paranormal phenomena and cognitive function, most of the findings align with the hypothesis that such beliefs are associated with cognitive differences or deficits. Charlotte E. Dean and colleagues at the University of Hertfordshire, U.K., present this evaluation in the open-access journal PLOS ONE on May 4.
For several decades, researchers have examined potential links between cognitive functioning and belief in paranormal phenomena, such as psychokinesis, hauntings, and clairvoyance. However, about 30 years have passed since a non-systematic review of this literature was last conducted. To provide updated insights into the findings and quality of studies on this topic, Dean and colleagues systematically identified and evaluated 70 published studies and one unpublished doctoral thesis produced between 1980 and 2020.
The 71 studies explored a range of cognitive functions, such as reasoning ability, thinking style, and memory. Overall, the findings align with the hypothesis that beliefs in paranormal phenomena are associated with differences or deficits in cognitive function. For example, a particularly consistent association was found between paranormal beliefs and an intuitive thinking style.
The review found that most of the 71 studies were of good methodological quality and that quality has improved over time; for instance, most had clear objectives and appropriate study designs. However, certain areas for improvement emerged; for instance, many studies lacked a discussion of their own methodological limitations, and undergraduate students made up a large portion of study participants, meaning that the findings may not necessarily apply to the general population.
The authors note that no specific profile of cognitive functioning for paranormal believers has emerged from this literature. They suggest that future research could not only address the methodological weaknesses they observed, but also explore the possibility that paranormal beliefs might be associated with a more overarching difference of cognition -- which could help explain why past studies have found links with seemingly disparate types of cognitive dysfunction.
The authors add: "Four decades of research suggests that belief in the paranormal is linked to our degree of cognitive flexibility and fluid intelligence; however, methodological improvements in future research are required to further our understanding of the relationship."
https://www.sciencedaily.com/releases/2022/05/220504144537.htm
Living in areas with more greenery may boost cognitive function
April 28, 2022
Science Daily/Boston University School of Public Health
Cognitive function at middle age is a strong predictor of whether a person may develop dementia later in life. Now, a new study led by a Boston University School of Public Health (BUSPH) researcher has found that increasing greenspace in residential areas could help improve cognition function in middle-aged women and that this association might be explained by a reduction in depression, which is also a risk factor for dementia.
Published in the journal JAMA Network Open, the study found that exposure to greenspace around one's home and surrounding neighborhood could improve processing speed and attention, as well as boost overall cognitive function. The results also showed that lowered depression may help explain the association between greenspace and cognition, bolstering previous research that has linked exposure to parks, community gardens, and other greenery with improved mental health.
"Some of the primary ways that nature may improve health is by helping people recover from psychological stress and by encouraging people to be outside socializing with friends, both of which boost mental health," says Dr. Marcia Pescador Jimenez, study lead and corresponding author, and assistant professor of epidemiology at BUSPH. "This study is among the few to provide evidence that greenspace may benefit cognitive function in older ages. Our findings suggest that greenspace should be investigated as a potential population-level approach to improve cognitive function."
For the study, Pescador Jimenez and colleagues from BUSPH, Harvard T.H. Chan School of Public Health, Brigham and Women Hospital, Harvard Medical School, and Rush Medical College estimated residential greenspace with a satellite image-based metric called the Normalized Difference Vegetation Index (NDVI). They measured psychomotor speed, attention, learning, and working memory among 13,594 women aged 61 on average and primarily White, from 2014 to 2016. The women were participants in the Nurses' Health Study II, the second of three studies that are among the largest investigations into the risk factors for chronic diseases among US women.
Adjusting for age, race, and individual and neighborhood socioeconomic status, the researchers found that greenspace exposure was associated with psychomotor speed and attention, but not learning or working memory.
In addition to depression, the researchers also examined the potential roles of air pollution and physical activity in explaining the association between greenspace and cognitive function, and they were surprised to only find evidence of depression as a mediating factor.
"We theorize that depression might be an important mechanism through which green space may slow down cognitive decline, particularly among women, but our research is ongoing to better understand these mechanisms," Pescador Jimenez says. "Based on these results, clinicians and public health authorities should consider green space exposure as a potential factor to reduce depression, and thus, boost cognition. Policymakers and urban planners should focus on adding more green space in everyday life to improve cognitive function."
While the study shows evidence of this association, the greenspace metric that the researchers used to measure greenspace exposure does not differentiate between specific types of vegetation. In a new project, Pescador Jimenez will apply deep learning algorithms to Google Street View images to better understand which specific elements of greenery, such as trees or grass, could be the driving factors for health.
The researchers also hope that their study is replicated among other racial/ethnic populations and assesses associations with cognitive decline over longer periods of time.
"The distribution of green spaces in cities is not uniform," says Pescador Jimenez. "Increasing everyday access to vegetation across vulnerable groups in urban cities is a crucial next step to achieve health equity."
https://www.sciencedaily.com/releases/2022/04/220427115708.htm
When it comes to preventing Alzheimer's, women respond better than men
April 26, 2022
Science Daily/Florida Atlantic University
A study is the first to examine if sex significantly affects cognitive outcomes in people who follow individually-tailored, multi-domain clinical interventions. The study also determined whether change in risk of developing cardiovascular disease (CVD) and Alzheimer's disease (AD), along with blood markers of AD risk, also were affected by sex. Results showed that while care in an Alzheimer's Prevention Clinic setting is equally effective at improving cognitive function in both women and men, the personally-tailored interventions used by the researchers led to greater improvements in women compared to men across AD and CVD disease risk scales, as well blood biomarkers of risk such as blood sugar, LDL cholesterol, and the diabetes test HbA1C. Findings are important because women are disproportionately affected by AD and population-attributable risk models suggest that managing risk factors can prevent up to one-third of dementia cases.
After increasing age, the most significant risk factor for Alzheimer's disease (AD) is sex -- two-thirds of patients with AD are females. In fact, even when accounting for gender-dependent mortality rates, age at death, and differences in lifespan, women still have twice the risk of incidence.
A study headed by Florida Atlantic University's Richard S. Isaacson, M.D., a leading neurologist and researcher, and collaborators from NewYork-Presbyterian/Weill Cornell Medicine, is the first to examine if sex significantly affects cognitive outcomes in people who follow individually-tailored, multi-domain clinical interventions. The study also determined whether change in risk of developing cardiovascular disease and AD, along with blood markers of AD risk, also were affected by sex. Other studies have focused on the role of hormones and sex-specific risk factors when examining differences in AD risk, but none have explored if these interventions result in differences in real-world clinical practice.
The study is an analysis of the Comparative Effectiveness Dementia & Alzheimer's Registry (CEDAR) trial launched at Weill Medicine in 2015 and spearheaded by Isaacson, which has already demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of AD in both women and men.
In the sub-group analysis, researchers evaluated the differential effectiveness of the clinical approach itself when considering sex in higher-compliance participants (n=80) from the original study cohort (n=154). Within this cohort, similar to the original study, participants were categorized by baseline diagnoses: normal cognition, subjective cognitive decline, and preclinical AD participants were classified as "Prevention." Mild cognitive impairment due to AD and mild AD were classified as "Early Treatment."
Results of the study, published in the Journal of Prevention of Alzheimer's Disease, showed that risk reduction care in an Alzheimer's Prevention Clinic setting led to improvements in cognition in both women and men without sex-differences. However, in the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA) than men. Women in the Early Treatment group also demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score and the MESA-RS. The CAIDE is a validated risk index that calculates late-life dementia risk based on midlife vascular risk factors such as body mass index, blood pressure, cholesterol and smoking status, while the MESA estimates one's risk of cardiovascular disease incidence over the next ten years using traditional risk factors.
"While care in an Alzheimer's Prevention Clinic setting is equally effective at improving cognitive function in both women and men, our personally-tailored interventions led to greater improvements in women compared to men across Alzheimer's and cardiovascular disease risk scales, as well blood biomarkers of risk such as blood sugar, LDL cholesterol, and the diabetes test HbA1C," said Isaacson, lead author and director of the newly launched FAU Center for Brain Health and the Alzheimer's Prevention Clinic within the Schmidt College of Medicine, who conducted the study while at Weill Cornell Medicine and NewYork-Presbyterian. "Our findings are important because women are disproportionately affected by Alzheimer's disease and population-attributable risk models suggest that managing risk factors can prevent up to one-third of dementia cases, highlighting the immense potential that lies in addressing modifiable risk factors."
After undergoing baseline clinical assessments, which included a detailed clinical history, physical examination, anthropometrics, blood biomarkers, apolipoprotein-?4 (APOE-e4) genotyping, and cognitive assessment, patients in the CEDAR study were given individually-tailored, multi-domain intervention recommendations informed by these clinical and biomarker data. Recommendation categories included patient education/genetic counseling, individualized pharmacological approaches (medications/vitamins/supplements), non-pharmacological approaches (exercise counseling, dietary counseling, vascular risk reduction, sleep hygiene, cognitive engagement, stress reduction, and general medical care) and other evidence-based interventions.
"Our latest results suggest that the individualized management approach used by the CEDAR study in a real-world clinic may offer equal cognitive benefits to both women and men, as well as better mitigation of calculated Alzheimer's disease and cardiovascular disease risk in women compared to men," said Isaacson. "Our work also highlights the need for larger studies focusing on sex differences in AD-related cognitive trajectories, as the existing body of knowledge lacks conclusive evidence on this issue."
Isaacson and collaborators are planning on larger cohorts to further define sex differences in AD risk reduction in clinical practice and hope to launch a multi-site international study soon to draw more definitive conclusions.
https://www.sciencedaily.com/releases/2022/04/220426101641.htm
An ocean in your brain: Interacting brain waves key to how we process information
Scientists show how the brain responds differently to seeing the same thing under different conditions
April 22, 2022
Science Daily/Salk Institute
For years, the brain has been thought of as a biological computer that processes information through traditional circuits, whereby data zips straight from one cell to another. While that model is still accurate, a new study led by Salk Professor Thomas Albright and Staff Scientist Sergei Gepshtein shows that there's also a second, very different way that the brain parses information: through the interactions of waves of neural activity. The findings, published in Science Advances on April 22, 2022, help researchers better understand how the brain processes information.
"We now have a new understanding of how the computational machinery of the brain is working," says Albright, the Conrad T. Prebys Chair in Vision Research and director of Salk's Vision Center Laboratory. "The model helps explain how the brain's underlying state can change, affecting people's attention, focus, or ability to process information."
Researchers have long known that waves of electrical activity exist in the brain, both during sleep and wakefulness. But the underlying theories as to how the brain processes information -- particularly sensory information, like the sight of a light or the sound of a bell -- have revolved around information being detected by specialized brain cells and then shuttled from one neuron to the next like a relay.
This traditional model of the brain, however, couldn't explain how a single sensory cell can react so differently to the same thing under different conditions. A cell, for instance, might become activated in response to a quick flash of light when an animal is particularly alert, but will remain inactive in response to the same light if the animal's attention is focused on something else.
Gepshtein likens the new understanding to wave-particle duality in physics and chemistry -- the idea that light and matter have properties of both particles and waves. In some situations, light behaves as if it is a particle (also known as a photon). In other situations, it behaves as if it is a wave. Particles are confined to a specific location, and waves are distributed across many locations. Both views of light are needed to explain its complex behavior.
"The traditional view of brain function describes brain activity as an interaction of neurons. Since every neuron is confined to a specific location, this view is akin to the description of light as a particle," says Gepshtein, director of Salk's Collaboratory for Adaptive Sensory Technologies. "We've found that in some situations, brain activity is better described as interaction of waves, which is similar to the description of light as a wave. Both views are needed for understanding the brain."
Some sensory cell properties observed in the past were not easy to explain given the "particle" approach to the brain. In the new study, the team observed the activity of 139 neurons in an animal model to better understand how the cells coordinated their response to visual information. In collaboration with physicist Sergey Savel'ev of Loughborough University, they created a mathematical framework to interpret the activity of neurons and to predict new phenomena.
The best way to explain how the neurons were behaving, they discovered, was through interaction of microscopic waves of activity rather than interaction of individual neurons. Rather than a flash of light activating specialized sensory cells, the researchers showed how it creates distributed patterns: waves of activity across many neighboring cells, with alternating peaks and troughs of activation -- like ocean waves.
When these waves are being simultaneously generated in different places in the brain, they inevitably crash into one another. If two peaks of activity meet, they generate an even higher activity, while if a trough of low activity meets a peak, it might cancel it out. This process is called wave interference.
"When you're out in the world, there are many, many inputs and so all these different waves are generated," says Albright. "The net response of the brain to the world around you has to do with how all these waves interact."
To test their mathematical model of how neural waves occur in the brain, the team designed an accompanying visual experiment. Two people were asked to detect a thin faint line ("probe") located on a screen and flanked by other light patterns. How well the people performed this task, the researchers found, depended on where the probe was. The ability to detect the probe was elevated at some locations and depressed at other locations, forming a spatial wave predicted by the model.
"Your ability to see this probe at every location will depend on how neural waves superimpose at that location," says Gepshtein, who is also a member of Salk's Center for the Neurobiology of Vision. "And we've now proposed how the brain mediates that."
The discovery of how neural waves interact is much more far-reaching than explaining this optical illusion. The researchers hypothesize that the same kinds of waves are being generated -- and interacting with each other -- in every part of the brain's cortex, not just the part responsible for the analysis of visual information. That means waves generated by the brain itself, by subtle cues in the environment or internal moods, can change the waves generated by sensory inputs.
This may explain how the brain's response to something can shift from day to day, the researchers say.
https://www.sciencedaily.com/releases/2022/04/220422161527.htm
Calming overexcited neurons may protect brain after stroke
New data prompts reconsideration of decades-old theory about brain injury due to stroke
April 21, 2022
Science Daily/Washington University School of Medicine
A new study has prompted scientists to reconsider a once-popular yet controversial idea in stroke research.
Neuroscientists believed that, in the aftermath of a stroke, calming overexcited neurons might prevent them from releasing a toxic molecule that can kill neurons already damaged by lack of oxygen. This idea was supported by studies in cells and animals, but it lost favor in the early 2000s after numerous clinical trials failed to improve outcomes for stroke patients.
But a fresh approach has yielded evidence that the idea may have been discarded too hastily. The new findings are available online in the journal Brain.
By scanning the whole genomes of nearly 6,000 people who had experienced strokes, researchers at Washington University School of Medicine in St. Louis identified two genes associated with recovery within the pivotal first 24 hours after stroke. Events -- good or bad -- that occur in the first day set stroke patients on their courses toward long-term recovery. Both genes turned out to be involved in regulating neuronal excitability, providing evidence that overstimulated neurons influence stroke outcomes.
"There's been this lingering question about whether excitotoxicity really matters for stroke recovery in people," said co-senior author Jin-Moo Lee, MD, PhD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "We can cure stroke in a mouse using blockers of excitotoxicity. But in humans we performed numerous clinical trials, and we couldn't move the needle. Every last one of them was negative. In this study, out of 20,000 genes, the top two genetic hits point to mechanisms involving neuronal excitation. That's pretty remarkable. This is the first genetic evidence that shows excitotoxicity matters in people and not just in mice."
Every year nearly 800,000 people in the U.S. have ischemic strokes, the most common kind of stroke. Ischemic strokes occur when a clot blocks a blood vessel and cuts off oxygen to part of the brain, triggering sudden numbness, weakness, confusion, difficulty speaking or other symptoms. Over the next 24 hours, some people's symptoms continue to worsen while others' stabilize or improve.
In the 1990s, Dennis Choi, MD, PhD, then head of the Department of Neurology at Washington University, performed groundbreaking research on excitotoxicity in stroke. He and others showed that stroke can cause neurons to release large amounts of glutamate, a molecule that transmits excitatory messages between neurons. Glutamate is constantly being released by neurons as part of the normal functioning of the nervous system, but too much all at once can be toxic. Efforts to translate this basic research into therapies for people did not pan out, and eventually pharmaceutical companies let their anti-excitotoxic drug development programs lapse.
But Lee, who formerly worked on excitotoxicity with Choi, did not give up. He teamed up with genetics researcher and co-senior author Carlos Cruchaga, PhD, the Barbara Burton and Reuben M. Morriss III Professor of Neurology and a professor of psychiatry; first author Laura Ibañez, PhD, an assistant professor of psychiatry; and co-author Laura Heitsch, MD, an assistant professor of emergency medicine and of neurology, to tackle the question of what drives post-stroke brain injury. The team identified people who had experienced strokes, and they looked for genetic differences between those who naturally recovered substantial function in the first day and those who did not.
As members of the International Stroke Genetics Consortium, the research team was able to study 5,876 ischemic stroke patients from seven countries: Spain, Finland, Poland, the United States, Costa Rica, Mexico and South Korea. They measured each person's recovery or deterioration over the first day using the difference between their scores on the National Institutes of Health (NIH) Stroke Scale at six and 24 hours after symptoms first appeared. The scale gauges a person's degree of neurological impairment based on measures such as the ability to answer basic questions such as "How old are you?"; to perform movements such as holding up the arm or leg; and to feel sensation when touched.
The researchers performed a genomewide association study by scanning the participants' DNA for genetic variations related to the change in their NIH stroke scale scores. The top two hits were genes that coded for the proteins ADAM23 and GluR1. Both are related to sending excitatory messages between neurons. ADAM23 forms bridges between two neurons so that signaling molecules such as glutamate can be passed from one to the other. GluR1 is a receptor for glutamate.
"We started with no hypotheses about the mechanism of neuronal injury," Cruchaga said. "We started with the assumption that some genetic variants are associated with stroke recovery, but which ones they are, we did not guess. We tested every single gene and genetic region. So the fact that an unbiased analysis yielded two genes involved in excitotoxicity tells us that it must be important."
In the years since anti-excitotoxic drug development was abandoned, clot-busting drugs have become the standard of care for ischemic stroke. Such drugs aim to restore blood flow so that oxygen -- and anything else in the bloodstream, including medication -- can reach affected brain tissue. Consequently, experimental neuroprotective therapies that failed in the past might be more effective now that they have a better chance of reaching the affected area.
"We know that that first 24-hour period has the greatest impact on outcomes," Lee said. "Beyond 24 hours, there's diminishing returns in terms of influence on long-term recovery. Right now, we don't have any neuroprotective agents for that first 24 hours. Many of the original studies with anti-excitotoxic agents were performed at a time when we weren't sure about the best trial design. We've learned a lot about stroke in the last few decades. I think it's time for a re-examination."
https://www.sciencedaily.com/releases/2022/04/220421181207.htm
Maladaptive daydreaming may be a better diagnosis for some than ADHD
April 12, 2022
Science Daily/Ben-Gurion University of the Negev
Maladaptive daydreaming (MD) may be a better diagnosis for some people than ADHD, according to a new study by Ben-Gurion University of the Negev researchers, in collaboration with the University of Haifa. MD is a condition whereby people slip into involved highly detailed and realistic daydreams that can last hours at the cost of normal functioning. It has not yet been recognized as a formal psychiatric syndrome. However, Dr. Nirit Soffer-Dudek of the Consciousness and Psychopathology Laboratory in the Department of Psychology at BGU is one of the foremost experts on the condition and is hoping to get MD added to the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM VI), by promoting rigorous research on the subject.
"Some individuals who become addicted to their fanciful daydreams experience great difficulty in concentrating and focusing their attention on academic and vocational tasks, yet they find that an ADHD diagnosis and the subsequent treatment plan does not necessarily help them. Formally classifying MD as a mental disorder would enable psychological practitioners to better assist many of their patients," says Dr. Soffer-Dudek.
Previous studies had found high levels of ADHD in those also presenting with MD, thereby raising the question of whether MD was separate from ADHD. In the current study, published recently in the Journal of Clinical Psychology, doctoral candidate Ms. Nitzan Theodor-Katz, together with Dr. Soffer-Dudek and their colleagues from the University of Haifa, assessed 83 adults diagnosed with ADHD for inattention symptoms, MD, depression, loneliness, and self-esteem. Of those, about 20% met the proposed diagnostic criteria for MD, with significantly higher rates of depression, loneliness, and lowered self-esteem, compared to those with ADHD that did not meet criteria for MD.
"Our findings suggest that there is a subgroup of those diagnosed with ADHD who would benefit more from a diagnosis of MD," says Dr. Soffer-Dudek.
https://www.sciencedaily.com/releases/2022/04/220412141107.htm
Certain personality traits associated with cognitive functioning late in life
People high in conscientiousness, low in neuroticism, less likely to develop mild cognitive impairment
April 11, 2022
Science Daily/American Psychological Association
People who are organized, with high levels of self-discipline, may be less likely to develop mild cognitive impairment as they age, while people who are moody or emotionally unstable are more likely to experience cognitive decline late in life, according to research published by the American Psychological Association.
The research, published in the Journal of Personality and Social Psychology, focused on the role three of the so-called "Big Five" personality traits (conscientiousness, neuroticism and extraversion) play in cognitive functioning later in life.
"Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan," said lead author Tomiko Yoneda, PhD, of the University of Victoria. "The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes."
Individuals who score high in conscientiousness tend to be responsible, organized, hard-working and goal-directed. Those who score high on neuroticism have low emotional stability and have a tendency toward mood swings, anxiety, depression, self-doubt and other negative feelings. Extraverts draw energy from being around others and directing their energies toward people and the outside world. They tend to be enthusiastic, gregarious, talkative and assertive, according to Yoneda.
To better understand the relationship between personality traits and cognitive impairment later in life, researchers analyzed data from 1,954 participants in the Rush Memory and Aging Project, a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois. Participants without a formal diagnosis of dementia were recruited from retirement communities, church groups, and subsidized senior housing facilities beginning in 1997 and continuing to the present. Participants received a personality assessment and agreed to annual assessments of their cognitive abilities. The study included participants who had received at least two annual cognitive assessments or one assessment prior to death.
Participants who scored either high on conscientiousness or low in neuroticism were significantly less likely to progress from normal cognition to mild cognitive impairment over the course of the study.
"Scoring approximately six more points on a conscientiousness scale ranging 0 to 48 was associated with a 22% decreased risk of transitioning from normal cognitive functioning to mild cognitive impairment," said Yoneda. "Additionally, scoring approximately seven more points on a neuroticism scale of 0 to 48 was associated with a 12% increased risk of transition."
Researchers found no association between extraversion and ultimate development of mild cognitive impairment, but they did find that participants who scored high on extraversion -- along with those who scored either high on conscientiousness or low in neuroticism -- tended to maintain normal cognitive functioning longer than others.
For example, 80-year-old participants who were high in conscientiousness were estimated to live nearly two years longer without cognitive impairment compared with individuals who were low in conscientiousness. Participants high in extraversion were estimated to maintain healthy cognition for approximately a year longer. In contrast, high neuroticism was associated with at least one less year of healthy cognitive functioning, highlighting the harms associated with the long-term experience of perceived stress and emotional instability, according to Yoneda.
Additionally, individuals lower in neuroticism and higher in extraversion were more likely to recover to normal cognitive function after receiving a previous diagnosis of mild cognitive impairment, suggesting that these traits may be protective even after an individual starts to progress to dementia. In the case of extraversion, this finding may be indicative of the benefits of social interaction for improving cognitive outcomes, according to Yoneda.
There was no association between any of the personality traits and total life expectancy.
Yoneda noted that the findings are limited due to the primarily white (87%) and female (74%) makeup of the participants. Participants were also highly educated, with nearly 15 years of education on average. Future research is necessary on more diverse samples of older adults and should include the other two of the big five personality traits (agreeableness and openness) to be more generalizable and provide a broader understanding of the impact of personality traits on cognitive processes and mortality later in life, she said.
https://www.sciencedaily.com/releases/2022/04/220411101359.htm
Loss of neurons, not lack of sleep, makes Alzheimer’s patients drowsy
Reviving 'awake neurons' could be the solution to their sleepiness
April 4, 2022
Science Daily/University of California - San Francisco
The lethargy that many Alzheimer's patients experience is caused not by a lack of sleep, but rather by the degeneration of a type of neuron that keeps us awake, according to a study that also confirms the tau protein is behind that neurodegeneration.
The study's findings contradict the common notion that Alzheimer's patients sleep during the day to make up for a bad night of sleep and point toward potential therapies to help these patients feel more awake.
The data came from study participants who were patients at UC San Francisco's Memory and Aging Center and volunteered to have their sleep monitored with electroencephalogram (EEG) and donate their brains after they died.
Being able to compare sleep data with microscopic views of their post-mortem brain tissue was the key to answering a question that scientists have been pondering for years.
"We were able to prove what our previous research had been pointing to -- that in Alzheimer's patients who need to nap all the time, the disease has damaged the neurons that keep them awake," said Grinberg, a neuropathologist who, along with psychiatrist Thomas Neylan, MD, is a senior author on the study, which appears in the April 4, 2022 issue of JAMA Neurology.
"It's not that these patients are tired during the day because they didn't sleep at night," noted Grinberg. "It's that the system in their brain that would keep them awake is gone."
The opposite phenomenon occurs in patients with other neurodegenerative conditions, such as progressive supranuclear palsy (PSP), who were also included in the study. Those patients have damage to the neurons that make them feel tired, so they are unable to sleep and become sleep deprived.
Grinberg's team developed the hypothesis that Alzheimer's patients were having trouble staying awake, after discovering a set of neurons that keep us awake and that are affected in Alzheimer's from the onset of the disease.
"You can think of this system as a switch with wake-promoting neurons and sleep-promoting neurons, each tied to neurons controlling circadian rhythms," said Joseph Oh, a medical student and one of the lead authors. "Finally, with this post-mortem tissue, we've been able to confirm that this switch, which is known to exist in model animals, also exists in humans and governs our sleep and awake cycles."
"Extremely Smart Neurons" Disrupted by Tau Proteins
Oh describes these neurons as "extremely smart" because they can produce an array of neurotransmitters and can excite, inhibit, and modulate other nerve cells.
"It's a small number of neurons but their computational capabilities are incredible," Oh said. "When these cells are affected by disease, it can have a huge effect on sleep."
To determine what's contributing to the degradation of these neurons in Alzheimer's, the researchers looked at the brains of 33 patients with Alzheimer's, 20 with PSP, and 32 volunteers who'd had healthy brains through the end of life.
The team measured the amounts of two proteins often associated with the neurodegenerative process -- beta amyloid and tau. Which of the two is more involved in disrupting sleep has been a long-disputed question, with most researchers crediting the sleep problems to beta-amyloid accumulation.
During sleep, the brain clears out the beta amyloid that accumulates during the day. When we can't sleep, it builds up. So, Neylan said, since the PSP patients never sleep, she expected to see lots of the protein in their brains.
"But it turns out that they have none," he said. "These findings confirm with direct evidence that tau is a critical driver of sleep disturbances."
In patients with PSP, said Grinberg, this understanding turned the treatment paradigm on its head.
"We see that these patients can't sleep because there is nothing telling the "awake" neurons to shut down," she said. "Now, rather than trying to induce these people to sleep, the idea is to shut down the system that's keeping them awake."
Clinical Trial is Giving Patients Hope
That idea is currently being tested in a clinical trial of patients with PSP, using a treatment that specifically targets the overactive 'awake' system that keeps these patients from sleeping. This approach contrasts with the traditional trial-and-error treatment with sleep medications.
At the helm of that trial is Christine Walsh, PhD, the study's other lead author, who has also worked on the study for a decade. Noting that PSP and Alzheimer's are at opposite ends of the sleep-disturbance spectrum, she said she expects the research to lead to new ways of treating sleep disturbances driven by neurodegeneration.
Treatments for Alzheimer's could be adjusted depending on the patient's needs, bumping up the "awake" system while tamping down the "sleep" system, said Walsh, who along with Grinberg, is a member of the UCSF Weill Institute for Neurosciences.
The PSP trial is still underway, and Walsh is highly optimistic that this new approach will have better results than current medications for people with either condition. Based on the findings of the study published today, she said, "We're even more hopeful that we can actually make a difference in the lives of these patients."
https://www.sciencedaily.com/releases/2022/04/220404120516.htm
Half of older adults now die with a dementia diagnosis, up sharply
More awareness and more detailed health records may explain rise; end-of-life care shifting as diagnoses allow for more advance planning
April 1, 2022
Science Daily/Michigan Medicine - University of Michigan
Nearly half of all older adults now die with a diagnosis of dementia listed on their medical record, up 36% from two decades ago, a new study shows.
But that sharp rise may have more to do with better public awareness, more detailed medical records and Medicare billing practices than an actual rise in the condition, the researchers say.
Even so, they note, this offers a chance for more older adults to talk in advance with their families and health care providers about the kind of care they want at the end of life if they do develop Alzheimer's disease or another form of cognitive decline.
The study, published in JAMA Health Forum by a University of Michigan team, uses data from 3.5 million people over the age of 67 who died between 2004 and 2017. It focuses on the bills their providers submitted to the traditional Medicare system in the last two years of the patients' lives.
In 2004, about 35% of these end-of-life billing claims contained at least one mention of dementia, but by 2017 it had risen to more than 47%. Even when the researchers narrowed it down to the patients who had at least two medical claims mentioning dementia, 39% of the patients qualified, up from 25% in 2004.
The biggest jump in the percentage of people dying with a dementia diagnosis happened around the time Medicare allowed hospitals, hospices and doctors' offices to list more diagnoses on their requests for payment.
But around this same time, the National Plan to Address Alzheimer's Disease also went into effect, with a focus on public awareness, quality of care and more support for patients and their caregivers.
The end-of-life care that patients with dementia received changed somewhat overtime, including a drop in the percentage who died in a regular hospital bed or a ICU bed, or who had a feeding tube in their last six months. The percentage who received hospice services rose dramatically, from 36% to nearly 63%, though the authors note this is in line with a national trend toward more hospice care by the late 2010s.
"This shows we have far to go in addressing end-of-life care preferences proactively with those who are recently diagnosed, and their families," said Julie Bynum, M.D., Ph.D., senior author of the study and a professor of geriatric medicine at Michigan Medicine. "Where once the concern may have been underdiagnosis, now we can focus on how we use dementia diagnosis rates in everything from national budget planning to adjusting how Medicare reimburses Medicare Advantage plans."
https://www.sciencedaily.com/releases/2022/04/220401122152.htm
Cases of cognitive decline in older people more than double in ten years
March 24, 2022
Science Daily/University College London
The researchers set out to see if there had been an increase in the numbers of older people who were reporting their first concerns about memory loss or cognitive decline to their doctor and what their chances of developing dementia were after consultation.
The study, published today in Clinical Epidemiology, looked at data from more than 1.3m adults aged between 65 and 99 years old, taken between 2009 and the end of 2018. The researchers identified 55,941 adults who had spoken to their GP about memory concerns and 14,869 people who had a record of cognitive decline.
For every 1,000 people that were observed for one year in 2009, there was one new case of cognitive decline being recorded. By 2018, for every 1,000 people that were observed for one year, there were three new cases of cognitive decline being recorded.
Lead author and PhD candidate Brendan Hallam (UCL Epidemiology & Health Care) said: "This is an important study which sheds new light on how prevalent memory concerns and cognitive decline are among the older generation in the UK and how likely these symptoms might progress to a dementia diagnosis.
"The study showed that while memory concern rates had remained stable, incidence of cognitive decline, a step beyond memory concern, had more than doubled between 2009 and 2018.
"There has been a drive in the past decade to encourage people to seek help earlier from their doctors if they are worried about their memory and we found that among those over 80, women and people living in more deprived areas were more likely to have a record of memory concern or cognitive decline, and their symptoms were more likely to progress to dementia diagnosis."
The study also showed that within three years of following up a person from the date when the doctor reported a memory concern, 46% of people would go on to develop dementia. For people with cognitive decline, 52% would go on to develop dementia.
Co-author, Professor Kate Walters (UCL Epidemiology & Health Care) explained: "People who have been noted in their health records as having concerns about their memory are at just under 50% chance of developing dementia within the next three years."
Brendan Hallam also outlined "Memory concerns and cognitive decline are not only hallmark symptoms of dementia, but they also predict a high risk of developing dementia. It is important for GPs to identify people with memory concerns as soon as possible to deliver recommendations to improve memory and allow timely diagnosis of dementia."
The authors note one potential limitation of the present study is the potential variations in which GPs record memory concerns and memory decline. They also say more research is needed to better understand the discrepancy between rates of memory symptoms and cognitive decline in the general population and those recorded in primary care.
https://www.sciencedaily.com/releases/2022/03/220324104459.htm