#cognitive decline
How the Eyes Might Be Windows to the Risk of Alzheimer’s Disease
Researchers say how quickly a person’s pupil dilates while taking cognitive tests
Alzheimer’s disease (AD) begins to alter and damage the brain years — even decades — before symptoms appear, making early identification of AD risk paramount to slowing its progression.
In a new study published online in the September 9, 2019 issue of the Neurobiology of Aging, scientists at University of California San Diego School of Medicine say that, with further developments, measuring how quickly a person’s pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins.
In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of protein plaques in the brain called amyloid-beta and tangles of a protein called tau. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.
The new study focuses on pupillary responses which are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is the earliest occurring known biomarker for AD; it first appears in the LC; and it is more strongly associated with cognition than amyloid-beta. The study was led by first author William S. Kremen, PhD, and senior author Carol E. Franz, PhD, both professors of psychiatry and co-directors of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine.
The LC drives pupillary response — the changing diameter of the eyes’ pupils — during cognitive tasks. (Pupils get bigger the more difficult the brain task.) In previously published work, the researchers had reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. Critically, in the latest paper, the scientists link pupillary dilation responses with identified AD risk genes.
“Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” said Kremen.
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Breastfeeding may help prevent cognitive decline
A new study led by researchers at UCLA Health has found that women over the age of 50 who had breastfed their babies performed better on cognitive tests compared to women who had never breastfed. The findings, published in Evolution, Medicine and Public Health, suggest that breastfeeding may have a positive impact on postmenopausal women’s cognitive performance and could have long-term benefits for the mother’s brain.
“While many studies have found that breastfeeding improves a child’s long-term health and well-being, our study is one of very few that has looked at the long-term health effects for women who had breastfed their babies,” said Molly Fox, PhD, lead author of the study and an Assistant Professor in the UCLA Department of Anthropology and the Department of Psychiatry and Biobehavioral Sciences. “Our findings, which show superior cognitive performance among women over 50 who had breastfed, suggest that breastfeeding may be ‘neuroprotective’ later in life.”
Cognitive health is critical for wellbeing in aging adults. Yet, when cognition becomes impaired after the age of 50, it can be a strong predictor of Alzheimer’s Disease (AD), the leading form of dementia and cause of disability among the elderly – with women comprising nearly two-thirds of Americans living with the disease.
Many studies also show that phases of a woman’s reproductive life-history, such as menstruation, pregnancy, breastfeeding and menopause can be linked to a higher or lower risk for developing various health conditions like depression or breast cancer, yet few studies have examined breastfeeding and its impact on women’s long-term cognition. Of those that have, there has been conflicting evidence as to whether breastfeeding might be linked to better cognitive performance or Alzheimer’s risk among post-menopausal women.
“What we do know is that there is a positive correlation between breastfeeding and a lower risk of other diseases such as type-2 diabetes and heart disease, and that these conditions are strongly connected to a higher risk for AD,” said Helen Lavretsky, MD, the senior author of the study and a professor in the Department of Psychiatry and Biobehavioral Sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Because breastfeeding has also been found to help regulate stress, promote infant bonding and lower the risk of post-partum depression, which suggest acute neurocognitive benefits for the mother, we suspected that it could also be associated with long-term superior cognitive performance for the mother as well,” added Dr. Fox.
To find out, the researchers analyzed data collected from women participating in two cross-sectional randomized controlled 12-week clinical trials at UCLA Health: 1) The “Brain Connectivity and Response to Tai Chi in Geriatric Depression and Cognitive Decline,” included depressed participants. 2) The “Reducing Risk for Alzheimer’s Disease in High-Risk Women through Yoga or Memory Training that included non-depressed participants with some subjective memory complaints and a risk for heart disease.
Among the two trials, 115 women chose to participate, with 64 identified as depressed and 51 non-depressed. All participants completed a comprehensive battery of psychological tests measuring learning, delayed recall, executive functioning and processing speed. They also answered a questionnaire about their reproductive life-history that included questions about the age they began menstruating, number of complete and incomplete pregnancies, the length of time they breastfed for each child and their age of menopause.
Importantly, none of the participants had been diagnosed with dementia, or other psychiatric diagnoses such as bipolar disorder, alcohol or drug dependence, neurological disorders or had other disabilities preventing their participation or taking any psychoactive medications. There was also no significant difference in age, race, education or other cognitive measures between the depressed and non-depressed participants.
Key findings from the researchers’ analysis of the data collected from questionnaires on the women’s reproductive history revealed that about 65% of non-depressed women reported having breastfed, compared to 44% of the depressed women. All non-depressed participants reported at least one completed pregnancy compared to 57.8% of the depressed participants.
Results from the cognitive tests also revealed that those who had breastfed, regardless of whether they were depressed or not, performed better in all four of the cognitive tests measuring for learning, delayed recall, executive functioning and processing compared to women who had not breastfed.
Separate analyses of the data for the depressed and non-depressed groups also revealed that all four cognitive domain scores were significantly associated with breastfeeding in the women who were not depressed. But in the women who were depressed, only two of the cognitive domains – executive functioning and processing speed – were significantly associated with breastfeeding.
Interestingly, the researchers also found that longer time spent breastfeeding was associated with better cognitive performance. When they added up all the time a woman spent breastfeeding in her life, they found that women who did not breastfeed had significantly lower cognitive scores in three out of four domains compared to women who had breastfed for 1-12 months, and in all four domains compared to the women who had breastfed for more than 12 months. Women who had breastfed the longest had the highest cognitive test scores.
“Future studies will be needed to explore the relationship between women’s history of breastfeeding and cognitive performance in larger, more geographically diverse groups of women. It is important to better understand the health implications of breastfeeding for women, given that women today breastfeed less frequently and for shorter time periods than was practiced historically,” said Dr. Fox.
Study could clarify how gut microbes can exacerbate cognitive decline
Recent research has found that changes in the gut microbiota — the trillions of bacteria and other microbes that live in the intestines — can alter the brain and behavior. Now, a study led by scientists at UCLA could elucidate how and why that phenomenon occurs.
In the experiment, which was conducted with mice, researchers found that gut microbes can exacerbate the effects of cognitive impairment because of how they affect the hippocampus, the region of the brain that is critical for memory and learning. They found that the concentration of one group of bacteria called Bilophila increased dramatically in the gut microbiota of mice that were fed a ketogenic diet — high in fat, and low in carbohydrates — and were intermittently deprived of oxygen, creating a condition called hypoxia.
The scientists also found that a ketogenic diet, hypoxia and treatment with a species of Bilophila called Bilophila wadsworthia impaired the hippocampus, leading to reduced cognitive ability in mice.
The research is published in the peer-reviewed journal Cell Host & Microbe.
The researchers gave several mice a ketogenic diet and others a standard diet. Then, all of the mice received reduced levels of oxygen for five consecutive days and then were given four days to recover. Depriving the animals of some oxygen was a way for the scientists to cause cognitive impairment, in order to mimic the cognitive impairment in humans that can be caused by neurological diseases or aging.
Next, the scientists observed their ability to navigate a maze. When trying to find their way out of a maze, mice on the ketogenic diet made an average of 30% more errors than mice given the standard diet. (The range of difference between the two groups was 25% to 75%.)
The researchers also evaluated whether the different diets alone could cause any change in cognitive behavior in mice who had not been deprived of oxygen. In that experiment, there was no appreciable difference in the mice’s ability to find their way out of the maze based on whether they had a ketogenic diet or a standard diet — indicating that the negative impact on cognitive ability only occurred in combination with oxygen deprivation.
“These results highlight the ability of different environmental factors to interact together to impact cognitive behavior in mice,” said lead author Christine Olson, a UCLA graduate student.
Next, the researchers investigated what would happen if they depleted the mice’s microbiota before administering a ketogenic diet and exposing them to hypoxia. Interestingly, mice that had their microbiota depleted first made significantly fewer errors in the maze than mice that were exposed to hypoxia and given a ketogenic diet but had not had changes to their microbiota first.
“This suggests that the microbes associated with the ketogenic diet and hypoxia could contribute to the detrimental effects on cognitive impairment,” Olson said.
The authors determined that Bilophila wadsworthia changes which genes are turned on or off in the hippocampus, and that the bacterium reduces normal cellular signaling in the hippocampus.
“Bilophila wadsworthia disrupted hippocampal activity and cognitive behavior in ways similar to how hypoxia and the ketogenic diet together did,” Olson said. She added that given the hippocampus’s important role in learning and memory, the changes offer clues for how Bilophila influences cognitive behavior.
Scientists are just now uncovering microbial species that can affect behavioral changes in mice and other animals, Hsiao said. She added that it will be important to study more specifically how microbial species can affect the brain — for example, through cellular changes that occur in response to microbes.
Cognitive impairment afflicts millions of people over age 65 and is associated with a wide variety of chronic metabolic, immunological and neurodegenerative disorders, such as Alzheimer’s disease. Elaine Hsiao, UCLA’s De Logi Professor of Biological Sciences and an associate professor of digestive diseases at the David Geffen School of Medicine at UCLA, said the new study could be an important step toward learning which microbes affect or impair cognitive ability.
“Identifying early risk factors is critical to enabling early detection and interventions for cognitive impairment,” said Hsiao, the paper’s senior author.
Hsiao added that more research is needed to determine whether other gut microbes besides Bilophila might also affect cognitive ability and whether the microbiota could influence cognitive decline in humans.
Insomnia in midlife may manifest as cognitive problems in retirement age
Insomnia in midlife may manifest as cognitive problems in retirement age
Long-term insomnia symptoms can pose a risk of poorer cognitive functioning later in life. This is why insomnia should be treated as early as possible, according to a new study.
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The Helsinki Health Study at the University of Helsinki investigated the development of insomnia symptoms in midlife and their effects on memory, learning ability and concentration after…
