1. New possibility of studying how Alzheimer’s disease affects the brain at different ages

    September 16, 2017 by Ashley

    From the Lund University press release:

    Alzheimer’s disease can lead to several widely divergent symptoms and, so far, its various expressions have mainly been observed through the behaviour and actions of patients. Researchers at Lund University in Sweden have now produced images showing the changes in the brain associated with these symptoms — a development which increases knowledge and could facilitate future diagnostics and treatment.

    Symptoms vary in cases of Alzheimer’s disease and often relate to the phase of life in which the disease first occurs. People who become ill before the age of 65 often suffer early on from diminished spatial perception and impaired orientation. Elderly patients more often suffer the symptoms traditionally associated with the disease: above all, memory impairment.

    “Now we have a tool which helps us to identify and detect various sub-groups of Alzheimer’s disease. This facilitates the development of drugs and treatments adapted to various forms of Alzheimer’s,” explains Michael Schöll, researcher at Lund University and the University of Gothenburg.

    Diagnostics could also be facilitated, mainly among younger patients in whom it is particularly difficult to arrive at a correct diagnosis.

    Confident in approval for clinical use

    The findings, published in the journal Brain, are based on studies of around 60 Alzheimer’s patients at Skåne University Hospital and a control group consisting of 30 people with no cognitive impairment.

    Once Alzheimer’s disease has taken hold, it gradually results in the tau protein, present in the brain, forming lumps and destroying the transport routes of the neurons. This can be clearly detected with the new imaging method.

    The method includes a device known as a PET camera and a trace substance, a particular molecule, which binds to tau. The imaging method is currently only used in research, where the current study is one of several contributing to increased knowledge about the disease:

    “The changes in the various parts of the brain that we can see in the images correspond logically to the symptoms in early onset and late onset Alzheimer’s patients respectively,” explains Oskar Hansson, professor of neurology at Lund University and consultant at Skåne University Hospital.

    Oskar Hansson believes that the imaging method will be in clinical use within a few years.


  2. A decline in navigational skills could predict neurodegenerative disease

    September 14, 2017 by Ashley

    From the Cell Press press release:

    Changes in how humans map their surroundings and construct and follow directions as they age have been understudied compared to effects on memory and learning. However, age-related declines in navigational ability are independent of those more well-known cognitive downturns, and could form the basis for tools for the early diagnosis of Alzheimer’s disease. Researchers discuss this possibility in a review published August 30 in the journal Neuron.

    “In humans, navigation is much more cumbersome to research than learning or memory,” says Thomas Wolbers, a neuroscientist specializing in aging and cognition at the German Center for Neurodegenerative Diseases. “But it has such a dramatic impact on everyday life, and the key structures of the ‘navigational network’ in the brain are very sensitive to both ordinary healthy aging and pathological factors.”

    Currently, Alzheimer’s disease is diagnosed based on an individual’s medical history, genetic risk factors, and performance on tests that measure memory, language, and reasoning impairments. Wolbers and his colleagues from the United States and the United Kingdom suggest that navigational impairments are among the earliest signs of the Alzheimer’s progression. Healthy older individuals, for instance, strongly prefer to map objects and landmarks relative to their body position (an egocentric strategy) rather than in relation to external objects such as global landmarks or boundaries (an allocentric strategy). This strategic bias makes it much more difficult for them to learn the spatial layout of an environment and can thus reduce their mobility, a worrisome sign in younger people.

    “It can take up to 10 years after the onset of Alzheimer’s for someone to show abnormal results on the standard cognitive tests that are available today, and that’s 10 years that you’ve lost for treating it, should an effective therapy come along down the road,” says Wolbers. “This is where navigation-based diagnostics could contribute, by reducing that window.”

    Navigational testing is held back by a pair of obstacles, though both are receding. The first is the lack of standard tests for navigational tasks and population norms with which to evaluate results. More-affordable and portable virtual reality technology is making standardized test conditions possible, however, while co-author Jan Wiener (@Jan_Wiener) of the United Kingdom’s Bournemouth University is one of the scientists behind the mobile app Sea Hero Quest, a game designed to collect population data on navigation decisions for dementia research.

    The second holdup is that navigational abilities vary wildly from person to person, more so than for memory or other cognitive functions, Wolbers says. An effective diagnostic tool might need to be longitudinal, tracking an individual’s navigation behaviors at different points in time throughout their life and looking for signs of early or accelerated decline. “We need longitudinal human data to be able to definitively say whether a change in navigational function can be used to predict whether Alzheimer’s or any other neurodegenerative disease will develop later on,” Wolbers says.

    With such data and the improved virtual reality setups, the researchers conclude that a navigational test battery analogous to those used for memory and learning will be feasible. For now, Wolbers suggests that people train and use the navigational skills hardwired into their brains, especially in an age of commonplace in-car and handheld GPS technology.

    “There is growing evidence that if you rely too much on that technology it can have a detrimental effect on your navigational ability and in the long term may even be a risk to develop pathological conditions,” he says.


  3. Noninvasive eye scan could detect key signs of Alzheimer’s disease years before patients show symptoms

    September 12, 2017 by Ashley

    From the Cedars-Sinai press release:

    Cedars-Sinai neuroscience investigators have found that Alzheimer’s disease affects the retina — the back of the eye — similarly to the way it affects the brain. The study also revealed that an investigational, noninvasive eye scan could detect the key signs of Alzheimer’s disease years before patients experience symptoms.

    Using a high-definition eye scan developed especially for the study, researchers detected the crucial warning signs of Alzheimer’s disease: amyloid-beta deposits, a buildup of toxic proteins. The findings represent a major advancement toward identifying people at high risk for the debilitating condition years sooner.

    The study, published in JCI Insight, comes amid a sharp rise in the number of people affected by the disease. Today, more than 5 million Americans have Alzheimer’s disease. That number is expected to triple by 2050, according to the Alzheimer’s Association.

    “The findings suggest that the retina may serve as a reliable source for Alzheimer’s disease diagnosis,” said the study’s senior lead author, Maya Koronyo-Hamaoui, PhD, a principal investigator and associate professor in the departments of Neurosurgery and Biomedical Sciences at Cedars-Sinai.

    “One of the major advantages of analyzing the retina is the repeatability, which allows us to monitor patients and potentially the progression of their disease.”

    Yosef Koronyo, MSc, a research associate in the Department of Neurosurgery and first author on the study, said another key finding from the new study was the discovery of amyloid plaques in previously overlooked peripheral regions of the retina. He noted that the plaque amount in the retina correlated with plaque amount in specific areas of the brain.

    “Now we know exactly where to look to find the signs of Alzheimer’s disease as early as possible,” said Koronyo.

    Keith L. Black, MD, chair of Cedars-Sinai’s Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute, who co-led the study, said the findings offer hope for early detection when intervention could be most effective.

    “Our hope is that eventually the investigational eye scan will be used as a screening device to detect the disease early enough to intervene and change the course of the disorder with medications and lifestyle changes,” said Black.

    For decades, the only way to officially diagnose the debilitating condition was to survey and analyze a patient’s brain after the patient died. In recent years, physicians have relied on positron emission tomography (PET) scans of the brains of living people to provide evidence of the disease but the technology is expensive and invasive, requiring the patient to be injected with radioactive tracers.

    In an effort to find a more cost-effective and less invasive technique, the Cedars-Sinai research team collaborated with investigators at NeuroVision Imaging, Commonwealth Scientific and Industrial Research Organisation, University of Southern California, and UCLA to translate their noninvasive eye screening approach to humans.

    The published results are based on a clinical trial conducted on 16 Alzheimer’s disease patients who drank a solution that includes curcumin, a natural component of the spice turmeric. The curcumin causes amyloid plaque in the retina to “light up” and be detected by the scan. The patients were then compared to a group of younger, cognitively normal individuals.

    Koronyo-Hamaoui and Koronyo also were key authors of the original results, published in the journal Neuroimage in 2011 and first presented at the Alzheimer’s Association’s International Conference in 2010.


  4. Less REM sleep tied to greater risk of dementia

    September 9, 2017 by Ashley

    From the American Academy of Neurology (AAN) press release:

    People who get less rapid eye movement (REM) sleep may have a greater risk of developing dementia, according to a new study published in the August 23, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. REM sleep is the sleep stage when dreaming occurs.

    There are five stages of sleep. Stage one is light sleep. Stage two is when the body begins to prepare for deeper sleep, including stages three and four. Stage five is REM sleep. During this dream stage, the eyes move rapidly and there is increased brain activity as well as higher body temperature, quicker pulse and faster breathing. The first REM stage occurs about an hour to an hour-and-a-half into sleep and then recurs multiple times throughout the night as the cycles repeat.

    “Sleep disturbances are common in dementia but little is known about the various stages of sleep and whether they play a role in dementia risk,” said study author Matthew P. Pase, PhD, of Swinburne University of Technology in Australia. “We set out to discover which stages of sleep may be linked to dementia and while we did not find a link with deep sleep, we did with REM sleep.”

    For the study, researchers looked at 321 people with an average age of 67 from Massachusetts who participated in The Framingham Heart Study. During that study, sleep cycles were measured for each participant. Researchers collected the sleep data and then followed participants for an average of 12 years. During that time, 32 people were diagnosed with some form of dementia and of those, 24 were determined to have Alzheimer’s disease.

    The people who developed dementia spent an average of 17 percent of their sleep time in REM sleep, compared to 20 percent for those who did not develop dementia. After adjusting for age and sex, researchers found links between both a lower percentage of REM sleep and a longer time to get to the REM sleep stage and a greater risk of dementia. In fact, for every percent reduction in REM sleep there was a 9 percent increase in the risk of dementia. The results were similar after researchers adjusted for other factors that could affect dementia risk or sleep, such as heart disease factors, depression symptoms and medication use.

    Other stages of sleep were not associated with an increased dementia risk.

    “Our findings point to REM sleep as a predictor of dementia,” said Pase. “The next step will be to determine why lower REM sleep predicts a greater risk of dementia. By clarifying the role of sleep in the onset of dementia, the hope is to eventually identify possible ways to intervene so that dementia can be delayed or even prevented.”

    Limitations of the study include a small sample size. Studies on larger groups of people need to be done to confirm findings. There was also no data available on shift work among study participants, which can cause unusual sleep patterns and possibly lead to sleep disorders.


  5. Toward an early Alzheimer’s test

    by Ashley

    From the Arizona State University press release:

    According to Paul Coleman, an Alzheimer’s researcher at the ASU-Banner Neurodegenerative Disease Research Center (NDRC), one of the greatest difficulties plaguing efforts to find effective treatments for Alzheimer’s is the enormous lag between the disease’s inception and the appearance of clinical symptoms.

    In a new study, Coleman and his colleagues demonstrate the promise of an early blood test for Alzheimer’s disease. The results suggest that Alzheimer’s can be detected even before the onset of symptoms in persons at genetic risk for Alzheimer’s disease.

    In addition to the NDRC, study collaborators include ASU, the Mayo Clinic, University of Rochester, Banner Alzheimer Institute and Barrow Neurological Institute.

    The new method successfully distinguished between Alzheimer’s, Parkinson’s and healthy controls, indicating that the test does not simply identify general phenomena of neurodegeneration but is able to pick out AD from other degenerative brain conditions.

    “What we’ve done in our paper is to replicate our own work multiple times with different populations and even using different technologies,” Coleman says. “We also presented data showing the ability to detect people at risk of a future diagnosis for Alzheimer’s disease.”

    The method accomplishes this feat by examining white blood cells or leucocytes. Here, segments of RNA known as transcripts — derived from specific DNA genes — hold vital clues regarding health.

    The study was recently published in the journal Neurobiology of Aging.

    Hidden menace

    Alzheimer’s disease continues its pitiless ascent. The illness afflicts 11 percent of those 65 or older, with the figure soaring to 45 percent for people over 85. Current trends predict some 14 million Americans will be afflicted with the disease by mid-century at a towering cost of a trillion dollars.

    Along its path of destruction, Alzheimer’s tears out its victim’s memory, reasoning capacity and personal identity, necessitating around-the-clock care, before death eventually ensues. The crippling toll of the disease on patients, family and society at large makes it a global health crisis of frightening proportions.

    Researchers now know that by the time the first outward manifestations of Alzheimer’s appear, in the form of confusion, memory loss and other classic hallmarks, Alzheimer’s has been ravaging the brain for decades. If the disease could be identified much earlier — close to its origin — there is hope that perhaps it could be slowed or even halted in its tracks.

    Given the vital need for a safe and reliable early diagnostic for Alzheimer’s, many previous efforts have taken aim at the problem. Ideally, such a method should be appropriate for primary care settings, allowing a broad swath of the public to be accurately and regularly tested.

    Until now, however, efforts to develop a reliable early diagnostic for Alzheimer’s have run aground. Further, the accuracy of diagnosis even after the disease has entered its clinical phase, remains poor.

    Signposts of disorder

    It has long been known that Alzheimer’s produces changes in the brain, which can stimulate genes relating to conditions like stress and inflammation. Expression of these genes appears in the blood in the form of specific RNA transcripts.

    The research results clearly demonstrate that these RNA transcripts can be combined into a potent early diagnostic or biomarker, able to distinguish normal patients from those with Alzheimer’s or Parkinson’s disease and — most importantly — make accurate predictions about patients at risk for future development of Alzheimer’s disease.

    The diagnostic precision of the new test is significant. Existing diagnostic screening results for known AD cases (identified through clinical and neuropathological factors), showed diagnostic sensitivity was between 71 percent and 87 percent while specificity ranged from 44 percent to 70 percent. (In medical diagnosis, sensitivity is the ability of a test to correctly identify those with the disease, known as the true positive rate, whereas specificity refers to the ability of the test to correctly identify those without the disease or the true negative rate.)

    Such diagnoses are typically conducted in specialized facilities devoted to the study of Alzheimer’s. As the authors note, the accuracy of standard diagnosis falls significantly in primary care settings. The result is that Alzheimer’s is generally detected very late in the disease process, if it is correctly identified at all — a blueprint for treatment failure, because the illness has already irreparably damaged the brain. The high rate of misdiagnosis leads to frequently unnecessary and ineffective treatment.

    Disease in the cross-hairs

    In a fresh approach, the authors identify RNA transcripts in blood using two different RNA-analysis techniques, known as cDNA array and reverse transcriptase polymerase chain reaction (RT-PCR). Results of the two methods were in close agreement and were further shown to be replicable across multiple sample populations. This allowed the researchers to design a consistent suite of transcripts that could be used to diagnose the disease. This multivariate analysis demonstrated impressive accuracy in a number of critical experiments described in the new paper.

    The study divides 177 blood and 27 post-mortem brain samples into several groups, establishing that careful analysis of RNA transcripts in blood samples has the ability to distinguish early clinical AD, Parkinson’s disease (PD), and cognitively healthy patients. It can accurately identify those carrying two copies of the APOE4 gene — known to be a severe risk factor for developing Alzheimer’s. Transcript screening was also used to identify those at risk for future cognitive impairment due to having at least one direct relative with AD.

    The study reveals that both cDNA and RT-PCR methods managed to distinguish probable AD from normal controls with an accuracy of 93.8 percent, using just 5 RNA transcripts for the test. As the authors note, the blood test’s’ accuracy may be even higher as some of the “false positives” — healthy cases mischaracterized as AD — may be from subjects who are actually positive for pre-symptomatic manifestations of Alzheimer’s.

    Assessing future risk

    The results demonstrate that multivariate analysis of transcripts in blood samples provide an accurate and minimally invasive strategy for diagnosis of AD and early detection of AD risk. Further, the results were consistent with examination of the same transcripts identified in the post-mortem brains of subjects with Alzheimer’s compared with those diagnosed with Parkinson’s disease and with normal controls. (The brain samples, obtained through the Banner Sun Health Research Institute, were taken from a region known to be vulnerable to the most devastating effects of Alzheimer’s.)

    In addition to RNA transcripts linked with inflammation and stress, the study examines a series of epigenetic transcripts — RNA sequences that have undergone post-transcriptional modification. Results again found a strong correlation between the presence of these epigenetic markers and AD, implying they may also provide a compelling diagnostic tool.

    Future refinements should sharpen the method’s ability to accurately identify Alzheimer’s disease at an early stage — prior to the onset of clinical symptoms — in a primary care setting, with just a simple blood extraction. Efforts to conduct long term longitudinal studies and hunt for additional diagnostic transcripts should eventually be combined with testing of new therapeutics aimed at early intervention.

    Intriguingly, one or more of the many existing drugs for Alzheimer’s which have failed in clinical trials, may actually succeed in slowing or arresting Alzheimer’s if they can be delivered early enough in the disease process. Further, trials for new drugs targeting at-risk patients can be ramped up significantly if a simple, non-invasive blood test can replace costly imaging like PET scan.

    The new early diagnostic therefore represents a promising milestone in the war on Alzheimer’s disease.


  6. Physical activity in midlife not linked to cognitive fitness in later years

    September 8, 2017 by Ashley

    From the Johns Hopkins University Bloomberg School of Public Health press release:

    A study led by Johns Hopkins Bloomberg School of Public Health researchers that tracked activity levels of 646 adults over 30 years found that, contrary to previous research, exercise in mid-life was not linked to cognitive fitness in later years.

    The finding suggests that physical activity may not help maintain cognitive function, or help avoid or delay the onset of the debilitating conditions like dementia and Alzheimer’s. Alzheimer’s affects as many as 30 million, mostly older people throughout the world. With no known treatment or cure, researchers are trying to identify measures that might help delay Alzheimer’s onset or limit its reach.

    The study, which appears online in the Journal of Alzheimer’s Disease, did find that activity levels among study participants in the later years were associated with high cognitive function two years later. This supports earlier research findings that exercise may help to maintain cognitive fitness in the short term.

    “This study reminds us that physical activity has all sorts of benefits for people, including promoting cardiovascular health, managing optimal weight levels and maintaining bone and muscle mass,” says Alden L. Gross, assistant professor in the Bloomberg School’s Department of Epidemiology. “Unfortunately it is too early for us to say the same about exercise and Alzheimer’s, especially as a possible long-term preventive measure.”

    There is no known treatment or cure for Alzheimer’s or dementia, syndromes that involves declining memory, confusion and eventually limited ability to perform daily tasks. To date, there are no preventive measures, such as physical exercise, brain games or a diet regimen, that have been proven to help delay or altogether prevent its onset. In the US, an estimated five million adults are currently living with Alzheimer’s, according to the Centers for Disease Control and Prevention (CDC), and the CDC predicts that this number will rise to 14 million by 2050.

    The researchers undertook the study because of a growing consensus that physical activity levels helps prevent Alzheimer’s, however much of the evidence for this thinking is based on cross-sectional studies that compare responses from one group of participants with another at a given point in time or within a very short duration, typically several years. Such studies can be valuable for confirming associations, or links, but not at establishing actual causation because of what is known as reverse causation: it is possible that people who eventually develop dementia may reduce their physical activity and exercise as dementia advances. That’s where longitudinal studies, which look at the same group of participants over a long time, are more helpful.

    The researchers used data from the Johns Hopkins Precursors study, which registered students studying at Johns Hopkins School of Medicine between 1948 and 1964 and tracked them with annual questionnaires about their overall health. The researchers note that the cohort’s homogeneity — students at a selective medical school — meant that any differences in physical activity and later cognitive function could not be explained by other differences among participants.

    The median age for study participants was 46 years in 1978 and 77 years in 2008. Every several years, the questionnaire asked about exercise, physical activity and physical limitations. The researchers used responses from 1978 through 2008 from 646 participants (598 men, 48 women) to calculate so-called metabolic equivalents, which quantify physical activity levels. Participants were also asked whether they regularly exercise to a sweat.

    The team administered cognitive tests in 2008, and, using participants’ medical records, scored for dementia through 2011. The researchers identified 28, or 4.5 percent of the cohort, to have Alzheimer’s.

    No physical activity measure in mid-life was associated with late-life cognitive fitness or onset of dementia. The study confirmed findings of other cross-sectional studies, that higher levels of physical activity and exercise measured close in time to the cognitive testing were associated with better cognitive functioning. The authors also looked at whether patterns of change in physical activity levels over the life span were associated with cognitive health and found no relationships.

    The idea that exercise might play a role in preventing or limiting Alzheimer’s makes sense, the researchers say, because physical activity, at least in mouse models, has shown less accumulation of B-amyloid plaques, which are thought to play a role in dementia, including Alzheimer’s. In addition, physical activity improves blood flow to the brain, which is linked to better cognitive performance. This may explain why studies find that exercise may contribute to cognitive fitness in the short term.

    “These findings have implications for intervention work moving forward,” says Gross. “We still need to focus on causes and mechanisms of Alzheimer’s and dementia, since we don’t yet know which preventive measures may or may not work. For now, when I speak in the community about Alzheimer’s, I find that people take some relief in understanding that there wasn’t anything that anyone might have done to avoid a loved one developing Alzheimer’s. Of course, the goal for researchers is to identify factors that may help older people maintain their cognitive function into their later years. More long-term studies like the Precursors study are needed.”


  7. Visual impairment among older adults associated with poor cognitive function

    September 7, 2017 by Ashley

    From the JAMA Network Journals press release:

    In a nationally representative sample of older U.S. adults, visual impairment was associated with worse cognitive function, according to a study published by JAMA Ophthalmology.

    The number of individuals in the U.S. with vision problems is anticipated to double by 2050. Visual dysfunction and poor cognition are highly prevalent among older adults; however, the relationship is not well defined. Suzann Pershing, M.D., M.S., of the Stanford University School of Medicine, Palo Alto, Calif., and colleagues conducted an analysis of two national data sets, the National Health and Nutrition Examination Survey (NHANES), 1999-2002, and the National Health and Aging Trends Study (NHATS), 2011-2015, to examine the association of measured and self-reported visual impairment (VI) with cognition in older US adults.

    The NHANES included 2,975 respondents, ages 60 years and older, who completed a test measuring cognitive performance. The NHATS included 30, 202 respondents ages 65 years and older with dementia status assessment. The researchers found that VI was significantly associated with worse cognitive function after adjusting for demographics, health, and other factors. These findings were most pronounced for visual acuity measured at distance and by self-report.

    The study notes some limitations, including that the results presented in this analysis are observational, and a causative relationship between VI and cognitive dysfunction cannot be established without longitudinal studies.

    “Further research is warranted to better understand longitudinal and causal relationships between visual and cognitive decline. However, from a policy perspective, should causality be established, this may contribute to the value of vision screening, not only to identify patients who may benefit from treatment of correctable eye diseases but also to suspect broader limitations in function from cognitive and directly visual tasks,” the authors write.


  8. Artificial intelligence predicts dementia before onset of symptoms

    September 6, 2017 by Ashley

    From the McGill University press release:

    Imagine if doctors could determine, many years in advance, who is likely to develop dementia. Such prognostic capabilities would give patients and their families time to plan and manage treatment and care. Thanks to artificial intelligence research conducted at McGill University, this kind of predictive power could soon be available to clinicians everywhere.

    Scientists from the Douglas Mental Health University Institute’s Translational Neuroimaging Laboratory at McGill used artificial intelligence techniques and big data to develop an algorithm capable of recognizing the signatures of dementia two years before its onset, using a single amyloid PET scan of the brain of patients at risk of developing Alzheimer’s disease. Their findings appear in a new study published in the journal Neurobiology of Aging.

    Dr. Pedro Rosa-Neto, co-lead author of the study and Associate Professor in McGill’s departments of Neurology & Neurosurgery and Psychiatry, expects that this technology will change the way physicians manage patients and greatly accelerate treatment research into Alzheimer’s disease.

    “By using this tool, clinical trials could focus only on individuals with a higher likelihood of progressing to dementia within the time frame of the study. This will greatly reduce the cost and the time necessary to conduct these studies,” adds Dr. Serge Gauthier, co-lead author and Professor of Neurology & Neurosurgery and Psychiatry at McGill.

    Amyloid as a biomarker of dementia

    Scientists have long known that a protein known as amyloid accumulates in the brain of patients with mild cognitive impairment (MCI), a condition that often leads to dementia. Though the accumulation of amyloid begins decades before the symptoms of dementia occur, this protein couldn’t be used reliably as a predictive biomarker because not all MCI patients develop Alzheimer’s disease.

    To conduct their study, the McGill researchers drew on data available through the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a global research effort in which participating patients agree to complete a variety of imaging and clinical assessments.

    Sulantha Mathotaarachchi, a computer scientist from Rosa-Neto’s and Gauthier’s team, used hundreds of amyloid PET scans of MCI patients from the ADNI database to train the team’s algorithm to identify which patients would develop dementia, with an accuracy of 84%, before symptom onset. Research is ongoing to find other biomarkers for dementia that could be incorporated into the algorithm in order to improve the software’s prediction capabilities.

    “This is an example how big data and open science brings tangible benefits to patient care,” says Dr. Rosa-Neto, who is also director of the McGill University Research Centre for Studies in Aging.

    While new software has been made available online to scientists and students, physicians won’t be able to use this tool in clinical practice before certification by health authorities. To that end, the McGill team is currently conducting further testing to validate the algorithm in different patient cohorts, particularly those with concurrent conditions such as small strokes.


  9. Noninvasive retinal imaging may improve early detection of Alzheimer’s disease

    September 2, 2017 by Ashley

    From the JCI Journals press release:

    Alzheimer’s disease (AD) represents the leading cause of dementia worldwide. Currently, challenges in making an early and definitive diagnosis of AD limit opportunities to intervene with disease-modifying therapies before substantial neurodegeneration occurs. Neurodegeneration in AD has been attributed to the accumulation of amyloid-? proteins (A?) in the central nervous system, and A? may be present up to 20 years prior to the onset of cognitive symptoms.

    Recently, noninvasive imaging techniques have been developed that can accurately detect and monitor A? deposition in the retinas of rodent AD models. The use of similar techniques to assess A? accumulation in human retinas may enable significant advances in early detection and treatment of AD.

    In this issue of JCI Insight, a study led by Maya Koronyo-Hamaoui at Cedars-Sinai Medical Center adapted a noninvasive retinal imaging approach to characterize A? deposition, the pathological hallmark of AD, in the retinas of AD patients and healthy controls. This live retinal imaging enabled the detection and quantification of A? plaques and revealed increased deposits in AD patients compared to controls. These positive results demonstrate the feasibility of this approach as a tool for screening those at risk of AD.


  10. Brain scan study adds to evidence that lower brain serotonin levels are linked to dementia

    August 27, 2017 by Ashley

    From the Johns Hopkins Medicine press release:

    In a study looking at brain scans of people with mild loss of thought and memory ability, Johns Hopkins researchers report evidence of lower levels of the serotonin transporter — a natural brain chemical that regulates mood, sleep and appetite.

    Previous studies from Johns Hopkins and other centers have shown that people with Alzheimer’s disease and severe cognitive decline have severe loss of serotonin neurons, but the studies did not show whether those reductions were a cause or effect of the disease. Results of the new study of people with very early signs of memory decline, the researchers say, suggest that lower serotonin transporters may be drivers of the disease rather than a byproduct.

    A report on the study, published in the September issue of Neurobiology of Disease, also suggest that finding ways to prevent the loss of serotonin or introducing a substitute neurotransmitter could slow or stop the progression of Alzheimer’s disease and perhaps other dementias.

    “Now that we have more evidence that serotonin is a chemical that appears affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression,” says Gwenn Smith, Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of geriatric psychiatry and neuropsychiatry at Johns Hopkins University School of Medicine.

    Serotonin levels that are lower and out of balance with other brain chemicals such as dopamine are well known to significantly impact mood, particularly depression, and drugs that block the brain’s “reuptake” of serotonin (known as SSRIs) are specific treatments for some major forms of depression and anxiety.

    Smith notes that researchers have tried with limited success to treat Alzheimer’s disease and cognitive impairment with antidepressants such as SSRIs, which bind to the serotonin transporters. But, since these transporters are at much lower levels in people with Alzheimer’s, she speculates that the drugs can’t serve their purpose without their target.

    The idea for Smith’s study was inspired by the work of co-author Alena Savonenko, M.D., Ph.D., associate professor of pathology, and her colleagues who showed that loss of serotonin neurons was associated with more protein clumps, or amyloid, in mouse brain.

    To further study serotonin’s role in cognition and neurodegenerative disease, the Johns Hopkins research team used brain positron emission tomography (PET) scans to look at levels of serotonin in the brains of people with mild cognitive problems, which may be early harbingers of Alzheimer’s disease or other dementias.

    For the study, the researchers recruited participants with community newspaper ads and flyers, as well as from the Johns Hopkins Memory and Alzheimer’s Treatment Center. They paired 28 participants with mild cognitive impairment to 28 healthy matched controls. Participants were an average age of 66 and about 45 percent were women. People with mild cognitive impairment were defined as those who have a slight decline in cognition, mainly in memory in terms of remembering sequences or organization, and who score lower on tests such as the California Verbal Learning Test, which requires participants to recall a list of related words, such as a shopping list. According to Smith, the inability to do this test accurately reflects changes in memory and cognitive impairment indicative of Alzheimer’s disease.

    Each participant underwent an MRI and PET scan to measure brain structures and levels of the serotonin transporter. During the PET scans, participants were given a chemical — similar in structure to an antidepressant but not a high enough dose to have a pharmacological effect — labeled with a radioactive carbon. The chemical binds to the serotonin transporter and the PET scanner detects the radioactivity. When a neuron sends a message it releases the neurotransmitter serotonin, which is detected by the next neuron receiving the message. After this nerve impulse transaction completes, the serotonin transporter SERT grabs up the serotonin and carts it back into the message-sending cell, a metabolic process marked by the ebb and flow of the chemical.

    Normally, as people age, the serotonin neurons are especially vulnerable to neurodegeneration, so the transporters are lost when these neurons die and serotonin levels go down. The older they are, the more likely a person is to have lower serotonin levels. That being said, the researchers found that people with mild cognitive impairment had up to 38 percent less SERT detected in their brains compared to each of their age-matched healthy controls. And not a single person with mild cognitive impairment had higher levels of SERT compared to their healthy control.

    Each participant also underwent learning and memory tests. In the California Verbal Learning Test, on a scale of 0 to 80, with 80 reflecting the best memory, the healthy participants had an average score of 55.8, whereas those with mild cognitive impairment scored an average of 40.5.

    With the Brief Visuospatial Memory Test, participants were shown a series of shapes to remember and draw later. From a scale of 0 to 36, with 36 being the top score, healthy people scored an average of 20.0 and those with mild cognitive problems scored an average of 12.6.

    The researchers then compared the results from the brain imaging tests for the serotonin transporter to those two memory tests, and found that the lower serotonin transporters correlated with lower scores. For example, those people with mild cognitive impairment had 37 percent lower verbal memory scores and 18 percent lower levels of SERT in the brain’s hippocampus compared to healthy controls.

    Smith says her group is investigating whether PET imaging of serotonin could be a marker to detect progression of disease, whether alone or in conjunction with scans that detect the clumping protein known as amyloid that accumulates in the brains of those with Alzheimer’s disease. When it comes to targeting the disease, because of reduced levels of the serotonin transporters, Smith says, the receptors that detect serotonin on message-receiving cells might be a better option. There are 14 types of serotonin receptors that could be used as possible targets. She says a number of experimental drugs now in clinical trials are designed to target serotonin in other ways in the brain, and may have better success than the SSRIs.

    About 5.5 million people in the U.S. have Alzheimer’s disease-caused dementia, and that number is expected to rise with the increasingly aging population.