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Keeping your brain active in old age has always been a smart idea, but a new study suggests that reading, writing letters and playing card games or puzzles in later life may delay the onset of Alzheimer’s dementia by up to five years. The research is published in the July 14, 2021, online issue of Neurology, the medical journal of the American Academy of Neurology.
“The good news is that it’s never too late to start doing the kinds of inexpensive, accessible activities we looked at in our study,” said study author Robert S. Wilson, PhD, of Rush University Medical Center in Chicago. “Our findings suggest it may be beneficial to start doing these things, even in your 80s, to delay the onset of Alzheimer’s dementia.”
The study looked at 1,978 people with an average age of 80 who did not have dementia at the start of the study. The people were followed for an average of seven years. To determine if they had developed dementia, participants were given annual examinations, which included a number of cognitive tests.
When the study began, people rated their participation in seven activities on a five-point scale. The questions included: “During the past year, how often did you read books?” and “During the past year, how often did you play games like checkers, board games, cards or puzzles?”
Participants also answered questions about cognitive activity in childhood, adulthood and middle age.
Researchers then averaged each person’s responses, with a score of one meaning once a year or less and score of five meaning every day or almost every day. People in the group with high cognitive activity scored an average of 4.0 which meant activities several times per week, compared to an average score of 2.1 for those with low cognitive activity, which meant activities several times per year.
During the study follow-up period, 457 people with an average age of 89 were diagnosed with Alzheimer’s dementia. People with the highest levels of activity, on average, developed dementia at age 94. The people with the lowest cognitive activity, on average, developed dementia at age 89, a difference of five years. The results were similar when researchers adjusted for other factors that could affect dementia risk, such as education level and sex.
To test the idea that low cognitive activity may be an early sign of dementia, not the other way around, researchers also looked at the brains of 695 people who died during the study. Brain tissue was examined for markers of Alzheimer’s like amyloid and tau protein deposits, but researchers found no association between how active they were cognitively and markers of Alzheimer’s disease and related disorders in their brains.
“Our study shows that people who engage in more cognitively stimulating activities may be delaying the age at which they develop dementia,” Wilson said. “It is important to note, after we accounted for late life level of cognitive activity, neither education nor early life cognitive activity were associated with the age at which a person developed Alzheimer’s dementia. Our research suggests that the link between cognitive activity and the age at which a person developed dementia is mainly driven by the activities you do later in life.”
A limitation of the study is that it was based on a group of mainly white people who had high levels of education. Further research will be needed to determine if the findings apply to the general population.
The study was supported by the National Institute on Aging.
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Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

What to Know About the Delta VariantEmily AnthesReporting on the coronavirusDoes the Delta variant cause different symptoms?It’s not clear yet. In Britain, reports have emerged that Delta may cause different symptoms than other variants do. Headaches, a sore throat and a runny nose are now among the most frequently reported symptoms.But the data are preliminary and a milder symptom profile could be a result of the fact that the variant is primarily infecting younger people, who are the least likely to be vaccinated.

Write down the benefits of obtaining a college degree and, more than likely, all the items on the completed list will relate to graduates: higher salaries, autonomous jobs and better access to health care, for instance. All of those factors, supported by extensive research, help draw a direct line connecting higher education and health. Similar research suggests how the education of parents affects their children.
Now, two University at Buffalo sociologists have used a new wave of data from a survey launched in 1994 to further extend the geometry linking educational attainment and health that demonstrates another dimension of the intergenerational effects of completing college. Their findings published recently in the Journal of Gerontology: Social Sciences suggest that adult children’s educational attainment has an impact on their parents’ mental and physical health.
“By analyzing these data we arrived at the conclusion that it was detrimental to parents’ self-reported health and depressive symptoms if none of their children completed college,” says Christopher Dennison, PhD, assistant professor of sociology in UB’s College of Arts and Sciences, and a co-author of the paper with UB colleague Kristen Schultz Lee, PhD, an associate professor in the Department of Sociology. “The negative mental health outcome of the parents was in fact our strongest finding.”
Dennison and Lee have both used the National Longitudinal Study of Adolescent to Adult Health (Add Health) in their previous research. Add Health is a nationally representative longitudinal study of over 20,000 adolescents. It is the largest such survey of its kind. There was an initial wave of data on the parents (ages 30-60) when the survey began and another wave of data from roughly 2,000 of those original participants (now ages 50-80) gathered from 2015-17.
It’s this latter data set that provided the researchers an opportunity to look at the intergenerational relationship between parents and children over time, while statistically balancing factors that could influence an aging parent’s health.
“These results are particularly important in light of growing educational inequalities in the U.S. in the last several decades,” says Lee. “We know how our own education impacts our own health; we know how parents’ education impacts their children in many different ways; now we’re trying to add to that understanding by explaining how children’s education can have an impact on their parents.

Uveal melanoma, or UM, is a rare and deadly cancer of the eye, and the mortality rate has remained unimproved for 40 years. Half of the melanomas spread to other organs of the body, causing death in less than a year, so new treatments to preserve vision and prevent death are an urgent need.
Now a preclinical study by researchers at the University of Alabama at Birmingham and Emory University, Atlanta, offers hope — a small molecule inhibitor has been identified that dampens the potent drivers of this tumor. In mouse models, the inhibitor, KCN1, strongly limited primary disease in the eye and metastatic tumor dissemination to the liver, and animals survived longer, without overt side effects.
Thus, this class of inhibitory compounds shows promise, though the co-leaders of the research — Erwin Van Meir, Ph.D., professor of neurosurgery at UAB, and Hans Grossniklaus, M.D., MBA, professor of ophthalmic pathology at Emory — say the drug needs further optimization before clinical use.
“Overall,” they wrote in the paper published in the journal Oncogene, “our preclinical studies support the further translation of the KCN1 arylsulfonamide scaffold toward a novel treatment for patients with metastatic uveal melanoma.” The uvea is the pigmented layer of the eye.
Prior to this study, it was known that: 1) a hypoxia gene signature, indicative of low oxygen levels in the tumor, is associated with poor prognosis and a high metastatic rate in uveal melanoma; 2) the hypoxia-inducible transcription factor, or HIF, turns on a large number of gene products with critical roles in cancer growth and metastasis; and 3) for UM specifically, HIF promotes tumor progression by regulating proliferation, migration, invasion and adhesion of tumor cells, as well as promoting blood vessel growth to feed the tumor.
Little was known of the role of HIF in directing pro-invasive extracellular matrix remodeling in UM. Changes in the extracellular matrix, including increased collagen deposition and reorganization of collagen fibers outside the cell, is known to aid cancer progression and tumor cell invasion. Extracellular matrix is the non-cellular component of all tissues that provides physical scaffolding for cells and has other biochemical roles.
Hypoxia promotes collagen deposition, in part, because HIF increases production of two gene products, P4HA1 and P4HA2, that are part of an enzyme complex that adds hydroxyl residues to prolines in procollagen. Procollagen is a precursor protein in the complex maturation process that collagen undergoes.
In their study, Van Meir, Grossniklaus and colleagues decided to evaluate the expression of the P4HA1/2 genes in relation to UM patient prognosis, and to determine whether inhibiting hypoxia-induced P4HA1/2 expression in a preclinical model of metastatic UM would yield therapeutic benefit.
They found that P4HA1 and P4HA2 were induced by hypoxia in human UM cell lines, and this induction was reduced by KCN1. Comparison of 46 patients with non-metastatic UM and 46 with metastatic UM showed that P4HA1/2 were significantly overexpressed in patients with metastatic disease. Also, P4HA1/2 expression correlated with poor overall survival in UM patients. This suggests that P4HA1 and P4HA2 can serve as prognostic markers in UM, and that they may be important for malignant progression of the disease and patient survival.
The researchers next turned to preclinical animal models of UM. They showed that KCN1 was abundantly taken up in the liver and the eyes after intraperitoneal injection, and it dampened tumor growth and disease burden at the primary site of the eye, as well as reduced distant metastases in the liver. KCN1 also increased survival in three different models that test the growth of human UM after injection in mice uvea. The inhibitor was most effective at reducing metastases when it was administered early.
At the molecular level, treatment with KCN1 to inhibit the hypoxic induction of P4HA1/2 decreased the hydroxylation of proline amino acids in the procollagen. It also caused cleavage of the collagen and disordered the structure of collagen VI, a mature structural component of the extracellular matrix. These collagen changes correlated with a reduction in tumor cell invasion.
“Our study,” Van Meir and Grossniklaus concluded, “suggests that KCN1 has desirable properties as a suppressor of metastasis: It is well tolerated, has excellent distribution to the eye and the liver, and is thus ideally suited for treating metastatic UM.”

A new study led by the U.S. Geological Survey outlines a means to better estimate COVID-19 occurrence and trends in populations.
Currently, COVID-19 testing is primarily limited to self-selected individuals, many of whom are symptomatic or have had contact with someone who is symptomatic. While these tests are useful for individual medical treatment and contact tracing, they do not provide health officials with a complete picture of the disease across the population.
“Coordinated sampling of COVID-19 is key to informing health officials as they continue their efforts to control the pandemic, permitting better predictions of disease dynamics and decisions that help limit transmission,” said James Nichols, USGS scientist emeritus and lead author of the study. “The proposed sampling methods should also help officials determine the effectiveness of vaccines, social distancing, masks and other mitigation efforts.”
By bringing its unique expertise in the design of data-gathering and monitoring systems, statistical analysis and mathematical modeling to human epidemiology, the USGS provides a means to fill the current information gap in testing data. This can benefit national and local governments and health officials as they develop interventions in response to new disease variants, plan for augmented vaccination efforts and prepare for future outbreaks.
With some countries experiencing surges in cases, Nichols points out, “the proposed testing strategies can be applied within the U.S. and internationally for COVID-19 and other diseases.”
One proposal in the study is to select a random sample within a population and survey those individuals for symptoms, such as elevated temperature, in order to gather more representative data on asymptomatic cases. This would help researchers estimate the proportion of symptomatic and asymptomatic individuals in the population.
The asymptomatic individuals, or a random subset of those individuals, could be tested for COVID-19 to help estimate infection probability for asymptomatic individuals in the population.
“The strategies outlined in this new research would help strengthen current testing approaches and could be done with relatively few additional tests and non-invasive surveys,” said Michael Runge, a USGS scientist and a co-author of the study. “Strategic testing, based on specific objectives, can provide information valuable for decisions about both individual healthcare and protecting communities.”
“It is critically important to be clear about the goal of a surveillance program,” said co-author Katriona Shea, a professor of biology and alumni professor in the biological sciences at Penn State. “Without knowing exactly what you want to achieve, how can you achieve it? A surveillance program for individual outcomes would be designed differently than a program aimed to understand population level public health objectives.”
Partners with the USGS in this study include Penn State, Lancaster University, the U.S. Department of Agriculture, University of Oxford, Stellenbosch University, University of Warwick and the National Institutes of Health.
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A previously unknown kind of human brain cell appears to help people center themselves in their personal maps of the world, according to a new study from neuroscientists at Columbia Engineering. This discovery sheds light on the cellular mechanisms underlying navigation and memory in humans, as well as what parts of the brain might get disrupted during the kinds of memory impairments common in neurodegenerative diseases such as Alzheimer’s.
There are two strategies with which humans and animals navigate and orient themselves. One involves locating places, distances and directions in “allocentric” or other-centered frames of reference rooted in the external world. The other strategy involves “egocentric” frames of reference that are centered on the self.
Whenever you use a mobile phone app to find driving directions, it will likely employ both these modes of navigation. When you first type in an address, it will normally show you the address on a map from an allocentric perspective, with ‘north’ at the top and ‘south’ at the bottom. When you then go to route view, it will switch to an egocentric perspective where ‘ahead’ is at the top and ‘behind’ is at the bottom.
Scientists first discovered brain cells linked with allocentric frames of reference in rats in 1971 — “place cells” that may, for example, indicate that one is located in the northeast corner of an area. Other allocentric spatial cell types include head-direction cells that may activate whenever one is navigating south, or border cells that may respond when a boundary is located to the west.
In the past decade, researchers began investigating how rat brains mapped egocentric frames of reference. Two years ago, scientists at Dartmouth College in Hanover, New Hampshire, identified a brain region in rats called the postrhinal cortex in which egocentrically tuned cells are abundant. However, it remained poorly understood what brain cells formed the basis of egocentric spatial maps in humans.
“In humans it is only rarely possible to directly record the activity of single neurons from the brain, due to ethical reasons,” said Lukas Kunz, a postdoctoral research scientist at Columbia University’s Department of Biomedical Engineering and first author of the new study. “There are techniques like fMRI or EEG, which allow us to indirectly measure neural activity from healthy human brains, but this neural activity reflects the sum activity of millions of neurons, which does not allow for direct conclusions about the working principles of single neurons.”
In the new study, neuroscientists from the United States and Germany investigated 15 epilepsy patients at the University of Freiburg’s Medical Center in Germany. These volunteers were implanted with electrodes to help doctors monitor their disorder.

People with diabetes and depression who take antidepressants may have a lower risk of death and of serious diabetes complications, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
People with diabetes face a higher risk of depression, which makes them more likely to die or develop diabetes complications including heart and kidney disease, stroke, eye, and foot problems. Depression makes diabetes complications worse due to stress, body weight changes, and lack of exercise.
“People with depression and diabetes have poorer health outcomes than those with diabetes alone, and regular antidepressant treatment could lower their risk of complications,” said study author Shi-Heng Wang, Ph.D., of the China Medical University in Taichung, Taiwan.
“People who adhere to their antidepressants have better diabetes outcomes and quality of life than those with poor adherence,” said study author Chi-Shin Wu, M.D., Ph.D., of the National Taiwan University Hospital in Taipei, Taiwan.
The researchers conducted a nationwide retrospective cohort study of 36,276 patients with depression and diabetes to determine if antidepressants could improve diabetes outcomes. They found regular antidepressant treatment was associated with a lower risk of death and heart disease.
Other authors of the study include: Le-Yin Hsu of the National Taiwan University in Taipei, Taiwan; and Yi-Jiun Pan of the China Medical University in Taichung, Taiwan.
The manuscript received funding from the Ministry of Science and Technology, the China Medical University, and the Ministry of Health and Welfare.
The manuscript, “Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus,” was published online, ahead of print.
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Researchers at Johns Hopkins Bloomberg School of Public Health have shown in a brain organoid study that exposure to a common pesticide synergizes with a frequent autism-linked gene mutation.
The results represent one of the clearest pieces of evidence yet that genetic and environmental factors may be able to combine to disturb neurodevelopment. Researchers suspect that genetic and environmental factors might contribute to the increased prevalence of autism spectrum disorder, a developmental disorder characterized by cognitive function, social, and communication impairments.
The study’s use of brain organoids also points the way towards quicker, less expensive, and more human-relevant experimentation in this field when compared to traditional animal studies.
The brain organoid model, developed by the Bloomberg School researchers, consists of balls of cells that are differentiated from human stem cell cultures and mimic the developing human brain. The researchers found in the study that chlorpyrifos, a common pesticide alleged to contribute to developmental neurotoxicity and autism risk, dramatically reduces levels of the protein CHD8 in the organoids. CHD8 is a regulator of gene activity important in brain development. Mutations in its gene, which reduce CHD8 activity, are among the strongest of the 100-plus genetic risk factors for autism that have so far been identified.
The study, which appears online July 14 in Environmental Health Perspectives, is the first to show in a human model that an environmental risk factor can amplify the effect of genetic risk factor for autism.
“This is a step forward in showing an interplay between genetics and environment and its potential role for autism spectrum disorder,” says study lead Lena Smirnova, PhD, a research associate in the Department of Environmental Health and Engineering at the Bloomberg School.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is highly transmissible, with nasal passages being the target of original infection. The nasal passage also shows the highest expression of ACE2, a protein that has been widely linked with increased susceptibility to COVID-19. Now, scientists from Japan have found that nasal inflammation can influence susceptibility to SARS-CoV-2. They also identified the use of short chain fatty acids as a potential COVID-19 management strategy.
Humans are no stranger to coronavirus (CoV) pandemics. Just like SARS-CoV-2 (the virus that causes COVID-19), another member of the coronavirus family — SARS-CoV — caused the severe acute respiratory syndrome (SARS) epidemic across parts of Asia in 2003. But, its spread was contained way faster than COVID-19. So, what makes SARS-CoV-2 so contagious?
Both SARS-CoV and SARS-CoV-2 viruses bear “spike proteins” which get inside our cells by binding to a protein called angiotensin-converting enzyme 2 (ACE2) that is found in our cells. However, the SARS-CoV-2 spike (S) protein has been found to have a higher binding affinity (10 to 20 times that of SARS-CoV) to ACE2, thus establishing a link between the pathogen and the protein.
Interestingly, recent studies have shown that patients with COVID-19 who have rhinosinusitis (i.e., inflammation of the nose) have a low risk of hospitalization. Moreover, the expression of ACE2 was reduced in patients with rhinosinusitis. Coincidentally, another study has shown that short-chain fatty acids (SCFAs), produced by bacteria in the gut have beneficial effects in allergy and viral infections. These separate findings prompted an investigation of the effect that SCFAs in the nasal cavity against SARS-CoV-2 infection by scientists from the University of Fukui, Japan, led by Dr. Tetsuji Takabayashi.
In a new study published in the American Journal of Rhinology & Allergy, the scientists attempted to understand the effect of SCFAs on ACE2 expression in the nasal passage, and the potential impact on COVID-19 infection. “This is the first report that short-chain fatty acids (SCFAs) effectively reduce the ACE2 levels in human airway epithelial cells,” remarks Dr. Takabayashi.
To understand the status of ACE2 expression in patients with allergies, the researchers studied the levels of ACE2 in the inner lining of the nose in patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis (CRS). Using techniques like real time-PCR to quantify the expression of ACE2, the researchers found that there was no increase in ACE2 expression in in patients with SAR-JCP, whereas it was decreased in patients with CRS.
To better understand the effect of SCFAs on ACE2 expression, the researchers cultured nasal epithelial cells and exposed them to either SFCA and double-stranded RNA (similar to the nuclear material found in some viruses and known to enhance ACE2 expression). Upon examining the expression of ACE2, the researchers saw that the SFCAs had suppressed ACE2 expression in the presence of the RNA as well.
These results suggest that SFCAs has potential therapeutic applications against COVID-19. Dr. Takabayashi explains, “The nasal mucosa exhibits the highest ACE2 expression among human organs and hence is a prominent target of original infection. Therefore, the development of strategies to downregulate ACE2 expression in nasal epithelial cells could reduce SARS-CoV-2 transmission and be useful as a novel therapeutic approach.”
The team’s timely findings will certainly aid in our fight against COVID-19.
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Materials provided by University of Fukui. Note: Content may be edited for style and length.

Heart attack, or myocardial infarction, is one of the leading causes of death worldwide. Although modern surgical techniques, diagnostics and medications have greatly improved early survival from these events, many patients struggle with the long-term effects of permanently damaged tissue, and the 5-year mortality rate remains high. Now, researchers reporting in ACS Nano have developed a minimally invasive exosome spray that helped repair rat hearts after myocardial infarction.
Scientists have explored using stem cell therapy as a way to regrow tissue after a heart attack. But introducing stem cells directly to the heart can be risky because they could trigger an immune response or grow uncontrollably, resulting in a tumor. Therefore, researchers have tried injecting exosomes — membrane-bound sacs containing proteins, lipids and nucleic acids secreted by stem cells — into the heart, but they often break down before they can have therapeutic effects. Others have developed cardiac patches, or scaffolds that help implanted exosomes last longer, but they usually must be placed on the heart during open-chest surgery. Yafeng Zhou and colleagues wanted to develop an exosome solution that could be sprayed onto the heart through a tiny incision, avoiding major surgery.
The researchers mixed exosomes from mesenchymal stem cells with fibrinogen, a protein involved in blood clotting. They added this solution to a tiny, double-barreled syringe that contained a separate solution of another clotting protein called thrombin. When the team sprayed the solutions out of the syringe onto a rat’s heart through a small chest incision, the liquids mixed and formed an exosome-containing gel that stuck to the heart. A mini-endoscope, inserted through a second small incision, guided the spray needle. In rats that had recently had a heart attack, the exosome spray lasted longer, healed injuries better and boosted the expression of beneficial proteins more than heart-injected exosomes. In pigs, the spray caused less severe immune reactions and surgical stress than open-chest surgery. The spray is a promising strategy to deliver therapeutic exosomes for heart repair, the researchers say.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.