Abstract
Study: Willingness to be screened for dementia varies by age but not by sex, race or income
INDIANAPOLIS -- The first study to examine the actual willingness of older adults to be screened for dementia has found that acceptance of screening is pervasive, although it varies by age. However, willingness to be screened for dementia does not differ by sex, race or income level.
Almost 90 percent of the 554 people in the study, who ranged in age from 65 to 96, indicated their willingness by undergoing actual screening. The odds of refusal were higher for patients age 70 to 79 than for those age 65 to 69 or for those age 80 or older. Refusal rates were lowest for those who ranged in age from 65 to 69.
Seventy percent of study participants were female, and slightly over half of those in the study were African-American. Three quarters of the older adults had an annual income of less than $20,000. Neither sex, race nor income level affected the study participants' willingness to undergo dementia screening. Refusal rates also did not vary by education level.
“Unlike past studies which asked about theoretical willingness to be screened for dementia and found less interest, we looked at actual willingness of primary care patients to be screened,” said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate professor of medicine at the Indiana University School of Medicine. A geriatrician, Dr. Boustani is the study's corresponding author and principal investigator. He is also medical director of the Healthy Aging Brain Center at Wishard Health Services, the public hospital where the study was conducted. The majority of older adults receive their health care from primary care physicians.
“We were surprised by the fact that only one in 10 older adults did not want to be screened for dementia, and we believe this finding of an extremely high level of acceptance of screening by our well-powered study will help doctors and the United States Preventive Services Task Force evaluate the benefits and harms of dementia screening by providing the voice and perceptions of patients,” said Dr. Boustani, who pointed out that if dementia screening is recommended in the future, special efforts will need to be employed to reach those in their 70s because of their higher rate of refusal.
"Effect of Patient Perceptions on Dementia Screening in Primary Care" appears in the June issue of the Journal of the American Geriatrics Society.
In addition to Dr. Boustani, co-authors of the study are Nicole R. Fowler, Ph.D. of the University of Pittsburgh; Amie Frame, MPH, and Anthony J. Perkins, M.S., of the Regenstrief Institute; Patrick Monahan, Ph.D. and Sujuan Gao, Ph.D., of the IU School of Medicine; and Greg A. Sachs, M.D., and Hugh C. Hendrie, M.B., Ch.B., D.Sc., of the Regenstrief Institute and the IU School of Medicine. Frame, Perkins and Drs. Monahan, Gao, Sachs and Hendrie are also with the IU Center for Aging Research, of which Dr. Boustani is associate director.
Study participants who indicated stronger agreement to statements about the benefits of knowing about dementia earlier (for example, ability to plan for the future) were more likely to accept screening. Of the 497 individuals screened in the study, 13 percent were found to be positive for dementia and were referred for a confirmatory diagnostic assessment. (Source: EurekAlert! A service of AAAS and Indiana University School of Medicine).
Attitude towards age increases risk of dementia diagnosis
Our attitude towards our age has a massive impact on the likelihood of being diagnosed with dementia. New research shows that when seniors see themselves as ‘older' their performance on a standard dementia screening test declines dramatically; making them five times more likely to meet the criteria for dementia.
The research, conducted by the University of Exeter, highlights the significance of our age perceptions and its effect on our mental functioning. It is presented today (Tuesday 12 June) at the first International Conference on Social Identity and Health. Hosted by the University of Exeter, the conference will cover community and public health, health in India, stress and resilience, and aging and dementia.
The research involved 68 people aged between 60 and 70 years, who were primed to either feel older or younger than others taking part in the study. Those in the ‘older' group were told the participants ranged in age from 40 to 70, encouraging them to think of themselves as being at the upper end of the age spectrum, while those in the ‘younger' group were told that participants ages ranged from 60 to 90 years, encouraging them to think of themselves at the lower end of the age spectrum. All participants were then given one of two articles to read, which either focused on the effects of age on memory loss or on the impact of ageing on general cognitive ability.
The participants then completed a series of standard clinical tests that included a standard dementia screening test, the Addenbrooke's Cognitive Examination-Revised. 70 per cent of people who were encouraged to see themselves as older and to believe that aging was associated with a general decline in ability, met the criterion for dementia. This was compared to an average of 14 per cent in the other groups.
The tests used in the study are the same as those used in memory clinics and GP surgeries to assist in dementia diagnosis. Therefore, the participants' sense of their own age had a major impact on widely-established clinical tools.
Lead author Dr Catherine Haslam of the University of Exeter said: “Our research shows that the effect of age perceptions on performance can be dramatic, and that seeing oneself as ‘older' significantly increases a person's risk of being diagnosed with dementia on such tests. It highlights the importance of taking a person's attitude towards their age into account when assessing for dementia.” (Source: EurekAlert! A service of AAAS and University of Exeter).
Diabetes, poor glucose control associated with greater cognitive decline in older adults
CHICAGO – Among well-functioning older adults without dementia, diabetes mellitus (DM) and poor glucose control among those with DM are associated with worse cognitive function and greater cognitive decline, according to a report published Online First by Archives of Neurology, a JAMA Network publication.
Findings from previous studies have suggested an association between diabetes mellitus and an increased risk of cognitive impairment and dementia, including Alzheimer disease, but this association continues to be debated and less is known regarding incident DM in late life and cognitive function over time, the authors write as background in the study.
Kristine Yaffe, M.D., of the University of California, San Francisco and the San Francisco VA Medical Center, and colleagues evaluated 3,069 patients (mean age, 74.2 years; 42 percent black; 52 percent female) who completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years.
At study baseline, 717 patients (23.4 percent) had prevalent DM and 2,352 (76.6 percent) were without DM, 159 of whom developed DM during follow-up. Patients who had prevalent DM at baseline had lower 3MS and DSST test scores than patients without DM, and results from analysis show similar patterns for 9-year decline with participants with prevalent DM showing significant decline on both the 3MS and DSST compared with those without DM.
Also, among participants with prevalent DM at baseline, higher levels of hemoglobin A1c (HbA1c) were associated with lower 3MS and DSST scores. However, after adjusting for age, sex, race and education, scores remained significantly lower for those with mid (7 percent to 8 percent) and high (greater than or equal to 8 percent) HbA1c levels on the 3MS but were no longer significant for the DSST.
“This study supports the hypothesis that older adults with DM have reduced cognitive function and that poor glycemic control may contribute to this association,” the authors conclude. “Future studies should determine if early diagnosis and treatment of DM lessen the risk of developing cognitive impairment and if maintaining optimal glucose control helps mitigate the effect of DM on cognition.” (Source: EurekAlert! A service of AAAS and JAMA and Archives Journals).
Role of omega-3 in preventing cognitive decline in older people questioned
Older people who take omega-3 fish oil supplements are probably not reducing their chances of losing cognitive function, according to a new Cochrane systematic review. Based on the available data from studies lasting up to 3.5 years, the researchers concluded that the supplements offered no benefits for cognitive health over placebo capsules or margarines, but that longer term effects are worth investigating.
Omega-3 fatty acids are fats responsible for many important jobs in the body. We get these fats through our daily diets and the three major omega-3 fats are: alpha linolenic acid (ALA) from sources such as nuts and seeds and eicosapentoic acid (EPA) and docosahexaenoic acid (DHA) from sources including oily fish such as salmon and mackerel. A number of studies have hinted that omega-3 fatty acids and DHA in particular may be involved in keeping nerve cells in the brain healthy into old age. However, there is limited evidence for the role of these fats in preventing cognitive decline and dementia.
The researchers, led by Emma Sydenham at the London School of Hygiene & Tropical Medicine (LSHTM), London, UK, gathered together evidence from three high quality trials comparing the effects of omega-3 fatty acids taken in capsules or margarine spread to those of sunflower oil, olive oil or regular margarine. A total of 3,536 people over the age of 60 took part in the trials, which lasted between six and 40 months. None of the participants had any signs of poor cognitive health or dementia at the start of the trials.
The researchers found no benefit of taking the omega-3 capsules or spread over placebo capsules or spread. Participants given omega-3 did not score better in standard mental state examinations or in memory and verbal fluency tests than those given placebo.
“From these studies, there doesn't appear to be any benefit for cognitive health for older people of taking omega-3 supplements," said Alan Dangour, a nutritionist at LSHTM and co-author of the report. "However, these were relatively short-term studies, so we saw very little deterioration in cognitive function in either the intervention groups or the control groups. It may take much longer to see any effect of these supplements.”
The researchers conclude that the longer term effects of omega-3 fatty acids on cognitive decline and dementia need to be explored in further studies, particularly in people with low intakes of omega-3 fatty acids in their diet. In the meantime, they stress other potential health benefits. “Fish is an important part of a healthy diet and we would still support the recommendation to eat two portions a week, including one portion of oily fish,” said Dangour. (Source: EurekAlert! A service of AAAS and JAMA and Wiley-Blackwell).
Key gene found responsible for chronic inflammation, accelerated aging and cancer
NEW YORK, May 24, 2012 – Researchers at NYU School of Medicine have, for the first time, identified a single gene that simultaneously controls inflammation, accelerated aging and cancer.
“This was certainly an unexpected finding,” said principal investigator Robert J. Schneider, PhD, the Albert Sabin Professor of Molecular Pathogenesis, associate director for translational research and co-director of the Breast Cancer Program at NYU Langone Medical Center. “It is rather uncommon for one gene to have two very different and very significant functions that tie together control of aging and inflammation. The two, if not regulated properly, can eventually lead to cancer development. It's an exciting scientific find.”
The study, funded by the National Institutes of Health, appears online ahead of print today in Molecular Cell and is scheduled for the July 13 print issue.
For decades, the scientific community has known that inflammation, accelerated aging and cancer are somehow intertwined, but the connection between them has remained largely a mystery, Dr. Schneider said. What was known, due in part to past studies by Schneider and his team, was that a gene called AUF1 controls inflammation by turning off the inflammatory response to stop the onset of septic shock. But this finding, while significant, did not explain a connection to accelerated aging and cancer.
When the researchers deleted the AUF1 gene, accelerated aging occurred, so they continued to focus their research efforts on the gene. Now, more than a decade in the making, the mystery surrounding the connection between inflammation, advanced aging and cancer is finally being unraveled.
The current study reveals that AUF1, a family of four related genes, not only controls the inflammatory response, but also maintains the integrity of chromosomes by activating the enzyme telomerase to repair the ends of chromosomes, thereby simultaneously reducing inflammation, preventing rapid aging and the development of cancer, Dr. Schneider explained.
“AUF1 is a medical and scientific trinity,” Dr. Schneider said. “Nature has designed a way to simultaneously turn off harmful inflammation and repair our chromosomes, thereby suppressing aging at the cellular level and in the whole animal.”
With this new information, Dr. Schneider and colleagues are examining human populations for specific types of genetic alterations in the AUF1 gene that are associated with the co-development of certain immune diseases, increased rates of aging and higher cancer incidence in individuals to determine exactly how the alterations manifest and present themselves clinically. (Source: EurekAlert! A service of AAAS and NYU Langone Medical Center / New York University School of Medicine).
Patient-derived stem cells could improve drug research for Parkinson's
NIH-funded study shows cells from different patients have unique drug responses
Researchers have taken a step toward personalized medicine for Parkinson's disease, by investigating signs of the disease in patient-derived cells and testing how the cells respond to drug treatments. The study was funded by the National Institutes of Health.
The researchers collected skin cells from patients with genetically inherited forms of Parkinson's and reprogrammed those cells into neurons. They found that neurons derived from individuals with distinct types of Parkinson's showed common signs of distress and vulnerability – in particular, abnormalities in the cellular energy factories known as mitochondria. At the same time, the cells' responses to different treatments depended on the type of Parkinson's each patient had.
The results were published in Science Translational Medicine.
“These findings suggest new opportunities for clinical trials of Parkinson's disease, in which cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention,” said Margaret Sutherland, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS).
A consortium of researchers conducted the study with primary funding from NINDS. The consortium is led by Ole Isacson, M.D., Ph.D., a professor of neurology at McLean Hospital and Harvard Medical School in Boston.
The NINDS consortium's first goal was to transform the patients' skin cells into induced pluripotent stem (iPS) cells, which are adult cells that have been reprogrammed to behave like embryonic stem cells. The consortium researchers then used a combination of growth conditions and growth-stimulating molecules to coax these iPS cells into becoming neurons, including the type that die in Parkinson's disease.
Parkinson's disease affects a number of brain regions, including a motor control area of the brain called the substantia nigra. There, it destroys neurons that produce the chemical dopamine. Loss of these neurons leads to involuntary shaking, slowed movements, muscle stiffness and other symptoms. Medications can help manage the symptoms, but there is no treatment to slow or stop the disease.
Most cases of Parkinson's are sporadic, meaning that the cause is unknown. However, genetics plays a strong role. There are 17 regions of the genome with common variations that affect the risk of developing Parkinson's disease. Researchers have also identified nine genes that, when mutated, can cause the disease.
Dr. Isacson and his collaborators derived iPS cells from five people with genetic forms of Parkinson's disease. By focusing on genetic cases, rather than sporadic cases, they hoped they would have a better chance of seeing patterns in the disease process and in treatment responses. Three of the individuals had mutations in a gene called LRRK2, and two others were siblings who had mutations in the gene PINK1. The researchers also derived iPS cells from two of the siblings' family members who did not have Parkinson's or any known mutations linked to it.
Because prior studies have suggested that Parkinson's disease involves a breakdown of mitochondrial function, the researchers looked for signs of impaired mitochondria in patient-derived neurons. Mitochondria turn oxygen and glucose into cellular energy. The researchers found that oxygen consumption rates were lower in patient cells with LRRK2 mutations, and higher in cells with the PINK1 mutation. In PINK1 mutant cells, the researchers also found increased vulnerability to oxidative stress, a damaging process that in theory can be counteracted with antioxidants.
Next, the researchers tested if neurons derived from patients and healthy volunteers were vulnerable to a variety of toxins, including some that target mitochondria. Compared to neurons from healthy individuals, patient-derived neurons were more likely to become damaged or die after exposure to mitochondrial toxins. Patient-derived neurons also suffered more damage from the toxins than did patient-derived skin cells.
Next, the researchers attempted to rescue the toxin-exposed cells with various drug treatments that have shown promise in animal models of Parkinson's, including the antioxidant coenzyme Q10 and the immunosuppressant rapamycin. All patient-derived neurons – whether they carried LRRK2 or PINK1 mutations – had beneficial responses to coenzyme Q10. However, the patient-derived neurons differed in their response to rapamycin; the drug helped prevent damage to neurons with LRRK2 mutations, but it did not protect the neurons with PINK1 mutations.
These results hint that iPS cell technology could be used to help define subgroups of patients for clinical trials. To date, interventional trials for Parkinson's disease have not focused on specific groups of patients or forms of the disease, because there have been few clues to point investigators toward individualized treatments. Although the current study focused on genetic forms of Parkinson's, iPS cell technology could be used to define disease mechanisms and the most promising treatments for sporadic Parkinson's as well.
The NINDS Parkinson's Disease iPS Cell Research Consortium is one of three such consortia funded by NINDS. One of the consortia is focused on developing iPS cells for the study of Huntington's disease, and another focuses on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
The Huntington's disease consortium recently reported successful derivation of iPS cells and iPS-generated neurons from patients. Cells from patients with both early and later onset disease showed severe defects in physiology, metabolism, and cell viability, compared to cells from healthy volunteers. These results were reported in the June 28th issue of Cell Stem Cell. The consortium is led by led by Leslie Thompson, PhD, a professor of psychiatry and human behavior at the University of California, Irvine.
Skin cell and iPS cell lines developed by the consortia are available to both academic and industry researchers through the NINDS human cell line repository at the Coriell Institute. To date the NINDS repository has distributed more than 200 cell lines worldwide.
The Parkinson's Disease iPS Cell Research Consortium is funded primarily by grants and contracts from NINDS (NS070276, NS078338). The three disease consortia were started in 2009 with more than $11 million in NINDS grants, made possible by the Recovery Act. Funding for the consortia was recently renewed through 2013 via a public-private partnership. Future goals include increasing the number of iPS cell lines and the variety of mutations represented, and giving some lines biological tags that will enable researchers to see when the cells have transformed into specific neuronal types. NINDS is funding this next phase in collaboration with the Michael J. Fox Foundation, the Parkinson's Disease Foundation, the ALS Association, the Association for Frontotemporal Degeneration, the CHDI Foundation, the Huntington's Disease Society of America, the Hereditary Disease Foundation, and the California Institute for Regenerative Medicine. (Source: EurekAlert! A service of AAAS and NIH/National Institute of Neurological Disorders and Stroke).
Researchers gain better understanding of mechanism behind tau spreading in the brain And the progression of Alzheimer's disease
Researchers at Mount Sinai School of Medicine have gained insight into the mechanism by which a pathological brain protein called tau contributes to the progression of Alzheimer's disease (AD) and other neurodegenerative disorders. This finding, published in the most recent issue of the Journal of Biological Chemistry, may provide the basis for future investigations on how to prevent tau from damaging brain circuits involved in cognitive function.
Previous studies have shown that the abnormal folding, or misfolding, and buildup of tau are key neuropathological features of many neurodegenerative disorders, including AD. Some research has demonstrated that AD-type tau neuropathology spreads in the brain, seemingly moving from one brain cell to another.
A research group led by Giulio Maria Pasinetti, MD, PhD, Saunders Family Chair in Neurology at Mount Sinai School of Medicine, explored whether misfolded tau released by neurons from the human brain – also known as paired helical filaments (PHFs) – could actually be taken up by surrounding cells and promote the spread of tau neuropathology. The evidence was gathered by treating human neuronal cell lines with human Alzheimer's disease-derived PHFs. The researchers found that not only did the cells in fact internalize the human PHFs, the abnormal tau then propagated its abnormal state to the native, normal tau protein in the cells.
“While these findings are potentially important for possibly opening new therapeutic avenues in Alzheimer's disease, they also shed light on a new therapeutic target for a wide variety of disorders sharing pathological features with Alzheimer's disease, for which there are currently no cures,” said Dr. Pasinetti. “Such diseases include Progressive Supranuclear Palsy, frontotemporal dementia, and other devastating neurodegenerative disorders in which misfolded tau forms aggregates in the brain.”
Next the researchers treated the same cell lines with a grape-seed extract enriched in polyphenols, which are natural compounds found in grapes, fruits, and vegetables, based on 2011 research showing the efficacy of this extract in preventing the progression of AD in mice. Dr. Pasinetti's group found that a subfraction of this natural grape-seed extract enriched in polyphenols was able to prevent the cell-to-cell spread of tau pathology in the same human neuronal cell lines.
“Pathology in neurodegenerative disorders is thought to be initiated decades before disease onset,” said Dr. Pasinetti. “While further research is needed in humans, we hypothesize that this grape-derived compound may be a promising therapy for not only treating but preventing neurodegenerative disorders involving tau neuropathology.”
Dr. Pasinetti and Jun Wang, PhD, Assistant Professor of Neurology at Mount Sinai, are named inventors of a pending application filed by Mount Sinai School of Medicine titled “Methods Preventing Neurodegenerative Disease” related to the use of grape-seed extracts for the treatment of neurodegenerative diseases and may benefit financially from this patent. (Source: EurekAlert! A service of AAAS and The Mount Sinai Hospital / Mount Sinai School of Medicine).
Parkinson's disease gene identified with help of Mennonite family: UBC-VCH research
An international team led by human genetic researchers at the University of British Columbia and Vancouver Coastal Health has identified the latest gene associated with typical late-onset Lewy body Parkinson's disease (PD), with the help of a Canadian Mennonite family of Dutch-German-Russian ancestry.
Twelve of the 57 members of the Saskatchewan family who participated in the study had previously been diagnosed with PD.
UBC Medical Genetics Prof. Matthew Farrer, who led the research, notes that unequivocal confirmation of the gene's linkage with PD required DNA samples from thousands of patients with PD and healthy individuals. He refers to the new discovery as the “missing link,” as it helps to unify past genetic discoveries in PD.
“A breakthrough like this would not be possible without the involvement and support of the Saskatchewan Mennonite family who gave up considerable time, contributed clinical information, donated blood samples, participated in PET imaging studies and, on more than one occasion following the death of an individual, donated brain samples,” says Farrer, Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience and the Dr. Donald Rix BC Leadership Chair in Genetic Medicine.
“We are forever indebted to their generosity and contribution to better understanding – and ultimately finding a cure – for this debilitating disease.”
The mutation, in a gene called DNAJC13, was discovered using massively parallel DNA sequencing. Conclusive evidence came from the identification of the gene mutation in several other families across many Canadian provinces, including British Columbia.
“This discovery is not only significant for researchers, but also for those families carrying this genetic mutation and afflicted with this disease in that it offers hope that something good might yet result from their suffering,” says Bruce Guenther, President of the Mennonite Brethren Biblical Seminary Canada, a community leader and spokesperson for the family that participated in the study.
“The family involved is very grateful for the research team's respectful, collaborative and sensitive approach, and we hope that this enables the discovery of more effective treatments, and hopefully eventually a cure.”
The discovery resulted from a longstanding collaboration with neurology colleagues, Ali and Alex Rajput at the University of Saskatchewan and Silke Cresswell and Jon Stoessl at UBC. The research team also includes scientists from McGill University, the Mayo Clinic in Florida, and St. Olav's Hospital in Norway.
Farrer shared the discovery last week with the medical community as part of his keynote speech in Dublin today at the 16th International Congress of Parkinson's Disease and Movement Disorders (Plenary Session V: Is it time to change how we define Parkinson's disease?) Details of the study was presented at the conference and is being submitted for publication.
“The identification of DNAJC13 will certainly be of interest to people around the world who trace their family history to the nineteenth-century Mennonite colonies in Russia, and who have family members suffering from Parkinson's disease,” Guenther adds.
BACKGROUND | New Parkinson's gene identified
Parkinson's disease (PD) is the second most common chronic neurodegenerative disorder after Alzheimer's. According to the U.S. National Institutes of Health, Parkinson's disease affects more than one million people in North America and more than four million people worldwide. The late-onset form is the most common type of PD. The risk of developing late-onset PD increases with age but most patients begin showing symptoms in their late 60s and early 70s.
Once considered a sporadic disease, latest studies have shown genetic components of PD that provide the foundation for neuroscience research and potential treatment targets.
Approximately 15 per cent of people with PD have a family history of the disorder. There is a higher rate of PD in families where two or more members are affected, possibly due to a shared genetic susceptibility among blood relatives.
UBC Prof. Matthew Farrer is an internationally renowned expert in the genetic aspects of PD and related dementia. He and his team have helped identified many genes involved in PD by analyzing DNA from families throughout the world.
Farrer and his research team are based at the Department of Medical Genetics at UBC's Faculty of Medicine, and at the Brain Research Centre at UBC and Vancouver Coastal Health Research Institute. He has had an adjunct Faculty in Medicine (Neurology) at the University of Saskatchewan since 2003. (Source: EurekAlert! A service of AAAS and University of British Columbia).