1. Study suggests surrogate decision makers experience psychological distress

    December 13, 2017 by Ashley

    From the Regenstrief Institute press release:

    Nearly half of the 13 million older adults hospitalized annually in the United States are unable to make their own medical decisions and rely on surrogates, usually close family members, to make decisions for them. However little is known about how these surrogates respond to the demands put upon them. A new study from the Indiana University Center for Aging Research and the Regenstrief Institute explores predictors and frequency of surrogate decision-maker distress and has found high levels of both anxiety and depression.

    The researchers report that provision of high levels of emotional support to surrogates during their family member’s hospitalization was associated with more effective decisions and lower surrogate anxiety, depression and post-traumatic stress.

    While emotional support (such as, “hospital staff really listened to me when we talked”) was associated with decision quality, surprisingly provision of information (“I [surrogate] received as much detail about my loved one’s care as I needed”) was less important.

    The researchers note that their study provides a detailed look at the relationship between clinician communication and psychological well-being of the family member. While this observational study does not prove causation, it raises the question of whether improved emotional support of surrogates could lead to both better decisions for the patient and better psychological outcomes for the surrogate.

    “Family decision makers face emotional, ethical and communication challenges that differ from personal decision making. It is not enough to provide good information; family members also need emotional support when making difficult decisions,” said corresponding author Alexia Torke, MD, the IU Center for Aging Research associate director, Regenstrief Institute investigator and IU School of Medicine associate professor of medicine, who led the study.

    “As the population ages and more and more family members are thrust into the role of surrogate decision makers, appropriately supporting these family members will become a public health imperative,” she said. Dr. Torke is the associate division chief of general internal medicine and geriatrics at IU School of Medicine and is also affiliated with the IU Health Fairbanks Center for Medical Ethics and Daniel F. Evans Center for Spiritual and Religious Values in Healthcare.

    A total of 364 patient-surrogate pairs from three hospitals were enrolled in the study. The average patient age was 82. Six out of ten patients were female and nearly three out of ten were African-American. Surrogates’ average age was 58 and 71 percent were female. Two thirds of surrogates were the patient’s adult children; 17 percent were the patient’s spouse.

    As many as 15 percent of the surrogate decision makers were found to suffer from clinically high levels of anxiety, depression or post-traumatic stress even six to eight weeks after the family member’s hospitalization. Some of the surrogate distress experienced during the acute illness resolved, but remained high for over 10 percent of surrogates. Surprisingly, anxiety and depression was not significantly higher for those making decisions for ICU patients than for other inpatients.

    “Even though high quality information is associated with overall satisfaction with the hospital stay, information without emotional support may be harmful to surrogates,” said Dr. Torke. “Improved emotional support could lead to both better decisions for the patient and better psychological outcomes for the surrogate. Physicians, nurses, chaplains and social workers can provide emotional support to family members. This study points to the fact that this support is very important.”


  2. Study identifies gene variant that protects against Alzheimer’s disease

    December 11, 2017 by Ashley

    From the Brigham Young University press release:

    Research published Wednesday in Genome Medicine details a novel and promising approach in the effort to treat Alzheimer’s disease.

    Brigham Young University professors Perry Ridge and John Kauwe led the discovery of a rare genetic variant that provides a protective effect for high-risk individuals — elderly people who carry known genetic risk factors for Alzheimer’s — who never acquired the disease.

    In other words, there’s a specific reason why people who should get Alzheimer’s remain healthy. Study authors believe this genetic function could be targeted with drugs to help reduce the risk of people getting the disease.

    “Instead of identifying genetic variants that are causing disease, we wanted to identify genetic variants that are protecting people from developing disease,” said Ridge, assistant professor of biology at BYU. “And we were able to identify a promising genetic variant.”

    That former approach to Alzheimer’s disease has been generally effective in producing a list of genes that might impact risk for the disease, but it leaves researchers without sufficient data on what to do next. In this new approach, Ridge and Kauwe develop the biological mechanism by which a genetic variant actually impacts Alzheimer’s disease.

    Using data from the Utah Population Database — a 20-million-record database of the LDS Church’s genealogical records combined with historical medical records from Utah — Ridge and Kauwe first identified families that had a large number of resilient individuals: those who carried the main genetic risk factor for Alzheimer’s (E4 Allele) but remained healthy into advanced age.

    Using whole genome sequencing and a linkage analysis methodology, they then looked for the DNA that those resilient individuals shared with each other that they didn’t share with loved ones who died of Alzheimer’s. They discovered the resilient subjects shared a variant in the RAB10 gene while those who got the disease did not share the genetic variant.

    Once the researchers identified the potentially protective gene variant, they over expressed it in cells and under expressed it in cells to see the impact on Alzheimer’s disease related proteins. They learned that when this gene is reduced in your body, it has the potential to reduce your risk for Alzheimer’s.

    “There are currently no meaningful interventions for Alzheimer disease; No prevention, no modifying therapies, no cure,” Kauwe said. “The discoveries we’re reporting in this manuscript provide a new target with a new mechanism that we believe has great potential to impact Alzheimer’s disease in the future.”


  3. Study suggests marriage may help stave off dementia

    December 7, 2017 by Ashley

    From the BMJ press release:

    Marriage may lower the risk of developing dementia, concludes a synthesis of the available evidence published online in the Journal of Neurology Neurosurgery & Psychiatry.

    Lifelong singletons and widowers are at heightened risk of developing the disease, the findings indicate, although single status may no longer be quite the health hazard it once seemed to be, the researchers acknowledge.

    They base their findings on data from 15 relevant studies published up to the end of 2016. These looked at the potential role of marital status on dementia risk, and involved more than 800,000 participants from Europe, North and South America, and Asia.

    Married people accounted for between 28 and 80 per cent of people in the included studies; the widowed made up between around 8 and 48 per cent; the divorced between 0 and 16 per cent; and lifelong singletons between 0 and 32.5 per cent.

    Pooled analysis of the data showed that compared with those who were married, lifelong singletons were 42 per cent more likely to develop dementia, after taking account of age and sex.

    Part of this risk might be explained by poorer physical health among lifelong single people, suggest the researchers.

    However, the most recent studies, which included people born after 1927, indicated a risk of 24 per cent, which suggests that this may have lessened over time, although it is not clear why, say the researchers.

    The widowed were 20 per cent more likely to develop dementia than married people, although the strength of this association was somewhat weakened when educational attainment was factored in.

    But bereavement is likely to boost stress levels, which have been associated with impaired nerve signalling and cognitive abilities, the researchers note.

    No such associations were found for those who had divorced their partners, although this may partly be down to the smaller numbers of people of this status included in the studies, the researchers point out.

    But the lower risk among married people persisted even after further more detailed analysis, which, the researchers suggest, reflects “the robustness of the findings.”

    These findings are based on observational studies so no firm conclusions about cause and effect can be drawn, and the researchers point to several caveats, including the design of some of the included studies, and the lack of information on the duration of widowhood or divorce.

    Nevertheless, they proffer several explanations for the associations they found. Marriage may help both partners to have healthier lifestyles, including exercising more, eating a healthy diet, and smoking and drinking less, all of which have been associated with lower risk of dementia.

    Couples may also have more opportunities for social engagement than single people — a factor that has been linked to better health and lower dementia risk, they suggest.

    In a linked editorial, Christopher Chen and Vincent Mok, of, respectively, the National University of Singapore and the Chinese University of Hong Kong, suggest that should marital status be added to the list of modifiable risk factors for dementia, “the challenge remains as to how these observations can be translated into effective means of dementia prevention.”

    The discovery of potentially modifiable risk factors doesn’t mean that dementia can easily be prevented, they emphasise.

    “Therefore, ways of destigmatising dementia and producing dementia-friendly communities more accepting and embracing of the kinds of disruptions that dementia can produce should progress alongside biomedical and public health programmes,” they conclude.


  4. Imaging technique shows progress Alzheimer’s disease

    December 4, 2017 by Ashley

    From the University of Twente press release:

    Using ‘Raman’ optical technology, scientists of the University of Twente in The Netherlands, can now produce images of brain tissue that is affected by Alzheimer’s disease. The images include the surrounding areas, already showing changes.

    Alzheimer’s disease is associated with areas of high protein concentration in brain tissue: plaques and tangles. Raman imaging is now used to get sharp images of these affected areas. It is an attractive technique, because it shows more than the specific proteins involved. The presence of water and lipids, influenced by protein presence, can also be detected. Using this technique, the researchers have studied brain tissue of four brain donors, three of them with Alzheimer’s disease.

    Transition

    The affected area can, in this way, be shown in a sharp and clear way. After image processing, even an area appears that is in transition between healthy and affected tissue: this may give an indication how the disease is spreading in the brain. Even in the brain tissue of the healthy person, a small area is detected with protein activity. This can be a first sign of a neurodegenerative disease.

    Raman microscopy uses a laser beam for the detection of chemical substances. The energy of the reflected and scattered light gives an indication of the substances present in a sample. In each of the four brain samples, 4096 spectra were examined in this way. A major advantage of Raman is that the chemicals don’t need a pretreatment, it is ‘label free’. In chemical analysis, Raman has proven to be a powerful technique.

    Cell level and smaller

    In this case, Raman was used to examine brain tissue outside the body, but it could even be used ‘in vivo’ for detecting specific areas during surgery. Compared to MRI, PET and CT imaging, Raman is able to detect areas, smaller than cells, with very high precision. In this way, it can be a very valuable extra technique. The Raman images now show protein activity at neural cell level, but the sensitivity is high enough for detecting areas that are even smaller — as is the case with the brain sample of the healthy person.

    Cees Otto, of the Medical Cell Biophysics group of UT, published his work in Scientific Reports, together with colleagues from Leiden University and from Spain and Austria.


  5. Study suggests social ties could help with cancer management

    December 3, 2017 by Ashley

    From the Brigham and Women’s Hospital press release:

    Researchers from Brigham and Women’s Hospital led by Ying Bao, MD, ScD, an epidemiologist in BWH’s Channing Division of Network Medicine and Assistant Professor at Harvard Medical School, have found that women with stronger social networks had better survival after colorectal cancer diagnosis and conclude that social network strengthening could be a tool for management of colorectal cancer.

    Colorectal cancer is the third most commonly diagnosed and second leading cause of cancer death in the United States. At current rates, approximately 5% of individuals will develop a cancer of the colon or rectum within their lifetime. Though social network research has been done in other diseased populations, very few studies have examined the association between social network and survival in varying cancer sites.

    The team utilized data from 896 women who participated in the Nurses’ Health Study and had been diagnosed with colorectal cancer between 1992 and 2012. Social integration was assessed every four years during that time using the Berkman-Syme Social Networks Index; the value scale accounts for factors like marital status, social network size, contact frequency and religious or social group participation. This helped organize a patient rating system that identified patients on a range from socially isolated to socially integrated.

    The findings indicated that, overall, women with high levels of social integration before a colorectal cancer diagnosis had significantly reduced risk of all-cause and colorectal cancer-specific mortality, particularly among older women. Though the number of extended ties (religious or social group participation) weren’t associated with survival, the presence of more intimate ties (family and friends) was associated with a significantly lower death rate.

    “When a patient is diagnosed, health care providers can look to the patient’s social network to see if it provides necessary resources or whether outside help might be something to consider,” said Bao who is also an assistant professor at Harvard Medical School. “That could be assistance from social workers, for example, to ensure access to care. For physicians, portions of a care plan aimed at strengthening a patient’s social network can be valuable tools that haven’t always been considered in the past.”

    Due to the complexity of network interactions, there are many pathways through which social networks could cause improved survival among cancer patients. Some prior research indicates that higher levels of social integration are associated with lower levels of inflammation and thus disease progression; other studies indicate it relates to a reduction in psychological stress and poor health behaviors that may contribute to cancer progression. Support from social networks, such as assistance in getting to medical appointments, reminders to take medications, and help with nutrition and mobility, may also explain the observed association. Future investigations are required to understand how these factors are influencing different kinds of patients and their care plans.


  6. Study suggests Alzheimer’s Tau protein forms toxic complexes with cell membranes

    December 2, 2017 by Ashley

    From the École polytechnique fédérale de Lausanne press release:

    The brains of patients with Alzheimer’s disease contain characteristic tangles inside neurons. These tangles are formed when a protein called Tau aggregates into twisted fibrils. As a result, the neurons’ transport systems disintegrate, essential nutrients can’t move through, and the cells begin to die, affecting the brain’s functions and giving rise to the disease’s symptoms.

    Given its role in the pathology of Alzheimer’s disease, Tau protein has been extensively investigated. With several clinical trials of amyloid-targeting therapies failing recently, Tau has become one of the most actively pursued therapeutic targets for Alzheimer’s disease. However, questions still remain about how Tau spreads in the brain and kills neurons. The cell membrane has been shown to play a role in regulating Tau’s aggregation properties and physiological functions, but we still do not understand how the interplay between Tau and lipid membranes can lead to the loss of neurons seen in Alzheimer’s disease.

    Now, the lab of Hilal Lashuel at EPFL, in collaboration with the lab of Thomas Walz at the Rockefeller University, found that individual Tau proteins interact with and disrupt the cell membrane of neurons. This disruption gives rise to highly stable complexes made up of several Tau proteins as well as fat molecules (phospholipids) from the membrane.

    Subsequent studies showed that the protein/phospholipid complexes are more readily taken up by neurons compared to the fibril form of the protein, and induce toxicity in primary neurons of the hippocampus in vitro. The hippocampus is where memory is processed, and loss of hippocampal neurons is a classic symptom of Alzheimer’s disease. The complexes were detectable with an antibody (MC-1) that is used as a standard for detecting pathological conformations of Tau, meaning that they share some features of the pathological form of the protein.

    “Our goal was to identify the sequence and structural factors that drive Tau interaction with membranes and the formation of these complexes so that we can develop strategies to interfere with their formation and block their toxicity,” says Nadine Ait Bouziad, the PhD student who led the study.

    In collaboration with Professor David Eliezer at Weill Cornell School of Medical Sciences in New York, the researchers used Nuclear Magnetic Resonance (NMR) to gain insight into the structure of Tau in the core of the complexes. This revealed that the cores are made up of two small peptides, each only six amino acids long. These peptides are called PHF6* and PHF6, and they play important roles in driving Tau aggregation and assembly into fibrils. Their presence connects the protein/phospholipid complexes with the development of Alzheimer’s disease.

    Building on their findings, the researchers were able to produce mutant Tau protein. The introduced mutations disrupted Tau’s ability to interact with cell membranes, but did so without interfering with its ability to form fibrils. The idea behind this is that such mutants can be used to uncouple these two processes, which would allow researchers to investigate the effect that these membrane interactions have on the function, aggregation and toxicity of Tau in primary neuron cultures. This would be a first step in gaining a clearer picture of how Tau tangles begin to form, which would be critical if we are to develop efficient therapies to counteract their toxicity.

    “Our findings point toward a novel form of Tau protein/phospholipid complexes that might be part of a membrane-dependent mechanism that regulates Tau structure, oligomerization, toxicity, and possibly its normal and aberrant trafficking between and within neurons,” says Hilal Lashuel. “By developing tools that allow us to detect, disrupt and/or target these complexes, we hope to identify novel strategies to inhibit Tau aggregation, toxicity, and pathology spreading in the Alzheimer’s brain.”


  7. Preliminary stages of dementia reduce human face memorization ability

    by Ashley

    From the Kumamoto University press release:

    A Japanese research group has revealed that elderly people with mild cognitive impairment (MCI) have a particularly weakened ability to memorize human faces in the short term when compared to healthy elderly people. MCI patients also had a different gaze behavior when trying to memorize a face. This research may lead to the early detection of dementia.

    Alzheimer’s disease is considered to be the most common type of dementia, and early detection of preliminary stages is important to halt its progression into a more serious form of the disease. MCI, which is thought to be a preliminary stage of Alzheimer’s, is a state in which cognitive functions, such as memory or thinking ability, decrease at a level that do not affect daily life.

    Brain imaging studies show that areas of the brain for memory and visually processing human faces in people with MCI are structurally and functionally transformed. To investigate these specific and yet unstudied areas, a research group from Kumamoto University in Japan conducted comparative experiments with normal elderly subjects and MCI patients (18 each) using a delayed-matching task with face and house stimuli in independent blocks. In each block, they asked subjects to remember a single image and then, after a short delay, select a memorized image from a set new of images. The researchers also recorded subject gaze trends during the image memorization process.

    Their experiments revealed that the memorization performance of MCI patients was lower for facial images than for house images, but found no performance difference in normal subjects. The research also showed that, during the memorization process, MCI patient gaze concentration on the eyes of an image decreased but the time spent looking at the mouth increased in comparison to normal subjects. In essence, MCI patients had reduced short-term memorization ability and a different gaze pattern for faces when compared to normal people.

    “Looking at the eyes is important for remembering the entirety of the face,” said Emeritus Professor Kaoru Sekiyama. “MCI patients probably have an abnormality in the cognitive processing of faces due to the deterioration of brain function. It is possible that the distributed gaze pattern is compensation for this decreased function. We hope to shed some light on this possibility in future work.”

    This research result was posted online in the journal Scientific Reports on 30 October 2017.


  8. New details on aged brain, Alzheimer’s and dementia

    November 30, 2017 by Ashley

    From the Allen Institute press release:

    In a comprehensive analysis of samples from 107 aged human brains, researchers at the Allen Institute for Brain Science, UW Medicine and Kaiser Permanente Washington Health Research Institute have discovered details that will help researchers better understand the biological bases for Alzheimer’s disease and dementia in older populations. The analysis also highlights surprising variability in the aged brain, including examples of donors with resilience to pathology. The research is published this month in the journal eLife, and the data underlying the research are publicly available as part of the suite of open data resources at the Allen Brain Atlas portal.

    “Since the population of individuals over 90 years of age is rapidly increasing, understanding both healthy aging and age-related disease is essential,” says Ed Lein, Investigator at the Allen Institute for Brain Science. “This means we must discover how cognitive decline correlates with the brain pathologies we typically attribute to diseases like Alzheimer’s in aged brains, as well as the biology underlying individual vulnerability and resilience to disease.” In this analysis, researchers sought to understand whether associations previously identified between cognitive status, gene expression and brain pathologies — such as the plaques and tangles typically found in Alzheimer’s disease — held true in a well characterized, aged population. To achieve this goal, researchers developed a state of the art approach combining traditional and quantitative measures to probe the relationships between gene expression and age-related neurodegeneration.

    “Several studies exist that compare expression in donor brains aged 60-85 years, but few in the more aged cohort we were able to study here,” says Jeremy Miller, Ph.D., Senior Scientist I at the Allen Institute for Brain Science and lead author on the publication. “We found that the more aged brains still showed a correlation between cognitive decline and the Alzheimer’s-associated plaques and tangles, although the relationship was not as strong as in younger cohorts.”

    In addition, the research revealed a surprising relationship between dementia and decreased quality of RNA — a key player in gene expression — in the more aged brain.

    “One factor that is not always taken into account when studying gene expression in the aged brain is the quality of the genetic material itself,” says Miller. “This variable is not necessarily related to any specific pathology or disease, but these results highlight the importance of properly controlling for RNA quality when studying the aged brain and indicate that degradation of genetic material may be an underappreciated feature of neurodegeneration or dementia.”

    All of the data underlying the research is part of the Aging, Dementia and TBI resource, freely available through the Allen Brain Atlas data portal. “We want to promote a model of systematic, collaborative, multidimensional study of the diseased brain and open access to data and tools to facilitate discovery across the entire basic and biomedical research community,” says Lein.

    “We anticipate that this dataset and research model will inform and help shape future brain aging research to propel a deeper understanding of the mechanisms driving neurological disease for improved diagnostic approaches and effective therapeutic strategies,” says C. Dirk Keene, M.D., Ph.D., study co-author and Director of UW Medicine Neuropathology.

    The study samples come from the Adult Changes in Thought (ACT) study, a longitudinal research effort led by Eric B. Larson, M.D., M.P.H., and Paul K. Crane, M.D., M.P.H., of the Kaiser Permanente Washington Health Research Institute (KPWHRI) (formerly known as Group Health Research Institute) and the University of Washington School of Medicine to collect data on thousands of aging adults, including detailed information on their health histories and cognitive abilities.

    “This collaboration with the Allen Institute for Brain Science has allowed us to gain insights never before possible into the relationships between neuropathology, gene expression, RNA quality, and clinical features tracked in the ACT study over more than 20 years,” says Larson, who has led the National Institute of Aging-supported study from its start in 1986 and is Vice President for Research and Health Care Innovation at Kaiser Permanente Washington. “We are grateful to the thousands of volunteer subjects who worked with us and those who donated their brains to science. The results are transformative in improving our understanding of the aging brain, a theme of the ACT study, which aims to learn ways to reduce the burden of dementia for individuals and society overall.”


  9. Intervention becomes first to successfully reduce risk of dementia

    by Ashley

    From the University of South Florida (USF Health) press release:

    Computerized brain-training is now the first intervention of any kind to reduce the risk of dementia among older adults. The breakthrough results from a randomized controlled trial were just published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions. The article, “Speed of Processing Training Results in Lower Risk of Dementia,” reports on the latest findings from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study funded by the National Institutes of Health.

    Speed of processing training resulted in decreased risk of dementia across the 10-year period of, on average, 29 percent as compared to the control,” said lead author Jerri Edwards, PhD, University of South Florida. “When we examined the dose-response, we found that those who trained more received more protective benefit.”

    The ACTIVE Study enrolled 2,802 healthy older adults at six sites around the United States and followed them for 10 years (as they aged from an average of 74 to 84). Participants were randomized into a control group or one of three intervention arms using different types of cognitive training: 1) a group receiving instruction on memory strategies; 2) a group receiving instruction on reasoning strategies; and 3) a group receiving individualized computerized speed of processing training. Participants in the cognitive training groups were offered 10 initial sessions of training (60-75 minutes per session) which was conducted over the first six weeks of the study.

    All participants were assessed on a number of cognitive and functional measures at the beginning of the study, after the first six weeks, and at 1, 2, 3, 5 and 10 years. Subsets of each intervention group also received four additional “booster” training sessions in months 11 and 35 of the study. Researchers found no significant difference in risk of dementia for the strategy-based memory or reasoning training groups, as compared to the control group. However, as compared to the control group, the computerized speed training group showed significantly less risk of dementia — averaging a 29 percent risk reduction.

    When reviewing the impact of each computerized speed training session completed, researchers found those who completed more sessions had lower risk. Among those who completed 15 or more sessions across all three intervention groups, the risk of dementia for the computerized speed training group was lowest at 5.9%, as compared to 9.7% and 10.1% for the memory and reasoning groups, respectively. The control group, which did not engage in any training, had a dementia incidence rate of 10.8%.

    Participants in the computerized speed training group were trained on a highly specific task designed to improve the speed and accuracy of visual attention, including both divided and selective attention exercises. To perform the divided attention training task, a user identified an object (i.e., car or truck) at the center of gaze while at the same time locating a target in the periphery (i.e., car). As the user got the answers correct, the speed of presentation becomes progressively briefer, while the targets become more similar. In the more difficult training tasks, the target in the periphery is obscured by distracting objects, engaging selective attention.

    There is substantial prior scientific literature on this training exercise, which is referred to as “speed of processing training,” “useful field of view training,” or “UFOV training.” The exercise was developed by Dr. Karlene Ball of the University of Alabama Birmingham and Dr. Dan Roenker of Western Kentucky University. It is now exclusively licensed to Posit Science Corporation, and is available as the “Double Decision” exercise of the BrainHQ.com brain training program.

    The paper notes that this particular type of computerized brain training, as updated by its inventors and Posit Science over the years, has previously been shown effective across more than 18 clinical trials in older adults on standard measures of cognitive abilities (e.g., speed of processing and attention) and functional abilities (e.g., maintaining the ability to live independently, depressive symptoms, feelings of control, and health-related quality of life), as well as in real world activities (e.g., driving safety, balance and gait).

    “We need to further delineate what makes some computerized cognitive training effective, while other types are not,” said Dr. Edwards. “We also need to investigate what is the appropriate amount of training to get the best results. The timing of intervention is also important. Existing data indicate speed training is effective among older adults with and without mild cognitive impairment, but it is important to understand this is preventative to lower risk of dementia and is not a treatment for dementia. Our ongoing research is examining this intervention among persons with Parkinson’s disease as well as other types of cognitive interventions.”

    The preliminary results reported at the Alzheimer’s Association International Conference were confirmed in this report. However, to be more conservative, the publication used a narrower definition of dementia. The article “Speed of Processing Training Results in Lower Risk of Dementia” reflects the ACTIVE study’s conclusion based on 3 criteria for dementia: cognitive and functional impairment, outcome of the Mini-Mental State Examination (MMSE) and/or diagnosis of dementia or Alzheimer disease as reported by the participant or a relative of the participant. The risk reduction from randomization to speed training ranged from 29-33%, depending on how dementia was defined.


  10. Brain astrocytes linked to Alzheimer’s disease

    November 26, 2017 by Ashley

    From the University of Eastern Finland press release:

    Astrocytes, the supporting cells of the brain, could play a significant role in the pathogenesis of Alzheimer’s disease (AD), according to a new study from the University of Eastern Finland. This is the first time researchers discovered a direct association between astrocytes and AD. Published in Stem Cell Reports, the study investigated the brain cell function of familial AD patients by using stem cell technologies.

    Alzheimer’s disease is the most common dementia type, with no treatment to slow down the progression of the disease currently available. The mechanisms of AD are poorly understood, and drug therapy has focused on restoring the normal function of neurons and microglia, i.e. cells mediating brain inflammation. The new study shows that astrocytes, also known as the housekeeping cells of the brain, promote the decline of neuron function in AD. The findings suggest that at least some familial forms of AD are strongly associated with irregular astrocyte function, which promotes brain inflammation and weakens neurons’ energy production and signalling.

    Astrocytes are important brain cells, as they support neurons in many different ways. Astrocytes are responsible, for example, for the energy production of the brain, ion and pH balance, and they regulate synapse formation, the connections between neurons. Recent evidence suggests that human astrocytes are very different from their rodent counterparts and thus, it would be essential to use human cells to study human diseases. However, the availability of human astrocytes for research has been very limited. The study carried out at the University of Eastern Finland used the induced pluripotent stem cell technology, which enables the generation of pluripotent stem cells from human skin fibroblasts. These induced stem cells can then be further differentiated to brain cells, e.g. neurons and astrocytes, with the same genetic background as the donor had.

    The study compared astrocytes from familial AD patients carrying a mutation in the presenilin 1 gene to astrocytes from healthy donors, and the effects of these cells on healthy neurons were also analysed.

    The researchers found out that astrocytes in patients with Alzheimer’s disease produced significantly more beta-amyloid than astrocytes in persons without AD. Beta-amyloid is a toxic protein that is known to accumulate in the brains of AD patients. In addition, AD astrocytes secreted more cytokines, which are thought to mediate inflammation. AD astrocytes also showed alterations in their energy metabolism which likely led to increased production of reactive oxygen species and reduced production of lactate, an important energy substrate for neurons. Finally, when astrocytes were co-cultured with healthy neurons, AD astrocytes caused significant changes on the signalling activity of neurons when compared to healthy astrocytes.

    This study was the first to show that astrocytes in patients with Alzheimer’s disease manifest many pathological changes typical of AD. Astrocytes could thus play a key role in the early stages of the disease and changes in the function of these cells could lead to neurodegeneration.

    “The induced pluripotent stem cells we used in this study proved to be extremely useful in disease modelling, and they could offer an excellent platform for drug discovery and testing new therapeutic targets for Alzheimer’s disease in the future,” says Early Stage Researcher Minna Oksanen, the lead author of the study.