2010 Alzheimer’s Disease Progress Report: A Deeper Understanding, the latest annual Alzheimer’s research report from the National Institutes of Health (NIH) , is now available online. Prepared by the National Institute on Aging, which leads the NIH effort conducting and supporting research on age-related cognitive decline and Alzheimer’s disease, the report highlights important developments and directions in NIH-funded research, including: risk for developing Alzheimer’s; genes that play a role in the disease; neuroimaging and biomarkers that detect and track the disease; research into new treatments; lifestyle factors that may worsen or protect against the disease; and help for caregivers. Special features include animation showing the progression of Alzheimer’s in the brain and video interviews highlighting new insights into the disease.
January 17, 2012
January 5, 2012
While most Americans depend on heating and air conditioning systems to keep comfortable during winter and summer, the body itself is a master regulator of temperature. The nervous system regulates the body’s heat production and dissipation through the skin, causing us to shiver when we are too cold and sweat when we are too hot. However, the genetic mechanisms driving sweat secretion are still largely unknown.
In the January 5, 2012 online issue of Proceedings of the National Academy of Sciences, investigators from NIA’s Laboratory of Genetics describe the first genetic cascade found to be involved in regulating sweat secretion. The scientists developed a strain of mice that lack FoxA1, a protein that controls when certain genes are activated, specifically in skin. They found that, while the mice did develop sweat glands, they did not sweat. This indicates that FoxA1 is involved in regulating sweat secretion. They also found evidence that two additional proteins, Best2 and NKcc1, were targets of FoxA1 and involved in the sweating process. The findings may provide future research direction for studying potential medicines that could protect against hyperthermia in extreme conditions, and alleviate reduced temperature regulation in older people.
Reference: Cui C.Y., et al. Forkhead transcription factor FoxA1 regulates sweat secretion through Bestrophin 2 anion channel and Na-K-Cl cotransporter 1. PNAS USA January 5, 2012. Epub ahead of print.
January 16, 2012
NIA and the World Health Organization (WHO) announce the availability of a new report, Global Health and Aging (PDF, 15.7M). As both the proportion of older people and the length of life increase throughout the world, key questions arise. Will population aging be accompanied by a longer period of good health, a sustained sense of well-being, and extended periods of social engagement and productivity, or will it be associated with more illness, disability, and dependency? How will aging affect health care and social costs? Are these futures inevitable, or can we act to establish a physical and social infrastructure that might foster better health and wellbeing in older age? How will population aging play out differently for low-income countries that will age faster than their counterparts have, but before they become industrialized and wealthy? This brief report, jointly issued by the WHO’s Department of Ageing and the Life Course and the NIA attempts to address some of these questions, emphasizing the central role that health will play in coming years.
January 10, 2012
A nicotine skin patch may improve cognition in older people with mild cognitive impairment (MCI), a condition marked by memory loss that often leads to Alzheimer’s dementia, according to findings from a small pilot clinical trial reported in the Jan. 10, 2012 print issue of Neurology. Nearly 70 volunteers, all non-smokers, wore either a nicotine patch or a placebo patch during the six month trial supported by the NIH. Researchers measured the volunteers’ cognitive performance at the start, at three months and at the end of the trial. They found the nicotine group showed significantly improved cognition during tests of mental speed, attention, and memory, and that the nicotine patch was safe to use for the trial period. Additionally, the nicotine group participants reported improved cognition, which was also noted by their caregivers. While the results of this small pilot trial were promising, the findings are not definitive and further investigation of a nicotine patch treatment for MCI in larger studies is warranted. Paul Newhouse, M.D., now of Vanderbilt University School of Medicine, Nashville, TN, led the trial while at the University of Vermont College of Medicine. The study was supported by the National Institute on Aging and the National Institute of General Medical Sciences, both parts of NIH at the U.S. Department of Health and Human Services.
Newhouse P., et al. Nicotine treatment of mild cognitive impairment: a six-month double-blind pilot clinical trial. Neurology January 10, 2012 78:91-101.
February 15, 2011
The U.S. Department of Veterans Affairs (VA) is expanding support nationally to caregivers of veterans with Alzheimer’s disease with a program developed by NIA-funded researchers. The REACH VA (Resources for Enhancing Alzheimer’s Caregiver Health in VA) program is the first national clinical implementation of a proven behavioral intervention for caregiver burden and stress. Results of the original REACH program were published in 2006.
REACH VA involved 127 caregivers connected to 24 VA medical centers. The median age for the caregiver was 72 and the majority of the participants were spouses. For 6 months, the REACH VA caregivers were provided with a number of options based on their needs: individual in-home and telephone counseling sessions; telephone support group sessions; a caregiver quick guide with 48 behavioral and stress topics; education on safety and patient behavior management; and training for their individual health and well-being.
Caregivers for veterans with Alzheimer’s disease and dementia typically reported feeling overwhelmed, frustrated, cut off from family and friends, lonely, prone to bouts of crying and having worse physical health than the year before. After participating in the REACH VA program, caregivers reported their burden reduced; drops in depressive symptoms; fewer frustrations, including those that have potential for abuse; and decreases in dementia-related behaviors from the veterans they cared for. Caregivers also reported they were able to spend fewer hours per day devoted to caregiving duties.
Nichols LO, Martindale-Adams J, Burns R, Graney MJ, Zuber J. Translation of a Dementia Caregiver Support Program in a Health Care System—REACH VA. Arch Intern Med. 2011;171(4):353-359.
February 19, 2011
Parkinson’s disease, a progressive movement disorder, was historically considered a nongenetic disease. Now, in the largest genome-wide association study to date of Parkinson’s disease, scientists show genetics play a substantial role in the disease. They have identified five new genomic regions in people of European ancestry and confirmed six previously identified regions that may contribute to increased disease risk.
The study, funded in part by the NIH, involved leading Parkinson’s research centers in the United States and Europe working together to pool DNA data from more than 33,000 participants. The researchers first scanned the genome to locate regions containing gene variants associated with Parkinson’s. To confirm these findings, they then looked for these suspect risk variants in DNA from an independent group of people with Parkinson’s or free of the disease. Based on these 11 risk variants, they found that those individuals who were in the top 20 percent in terms of genetic risk were more than two and a half times as likely to have the disease than those who were in the bottom 20 percent of the genetic risk spectrum.
“Up until just 10 or 15 years ago, the field did not think genetics played much of a role in the development of Parkinson’s disease,” said Dr. Andrew Singleton, chief of NIA’s Laboratory of Neurogenetics and co-author of the study. “This work not only increases our understanding of how genes are involved in the disease process, but with more research, may one day result in the development of better diagnostics and therapeutic interventions for this debilitating disease.”
International Parkinson Disease Genomics Consortium. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet. 2011 Feb 19;377(9766):641-9. Epub 2011 Feb 1.
Oregon health insurance lottery shows access to insurance increases health care use; improves well-being, decreases financial strainJuly 7, 2011
The first results of the 2008 Oregon health insurance lottery study, supported in part by the NIA, indicate that people enrolled in the state’s Medicaid program reported improved health and well-being, as well as reduced financial strain. They also saw an increase in use of primary and preventive care as well as hospitalizations. Program expenditures rose as a result of the rise in utilization. The study results were reported in a National Bureau of Economic Research (NBER) Working Paper, in a collaboration between NBER researchers and the state of Oregon.
The Oregon program randomly assigned 10,000 low-income uninsured adults to the state’s Medicaid program. Participants were chosen from about 90,000 people who signed up for the lottery program. After 1 year, the study found that enrollment in Medicaid increased the likelihood of using outpatient care by 35 percent, using prescription drugs by 15 percent, and having a regular office or clinic for primary health care by 70 percent among those with insurance. The probability of having an unpaid medical bill sent to a collection agency decreased by 25 percent among those in the program. The probability of people reporting themselves in good to excellent health (compared with fair or poor health) increased by 25 percent among those with insurance. The increased use of health care services resulted in an estimated 25 percent increase in annual health care expenditures.
The researchers note that these findings are part of a broader study that will continue to follow the participants in the program. Ongoing work will provide more information on the effects of expanded insurance, including specific clinical indicators and health outcomes measured over 2 years; the current study covers the first year of the lottery. Together, this information will facilitate the evaluation of costs and benefits of insurance expansions.
Finkelstein, A., et al. The Oregon Health Insurance Experiment: Evidence from the First Year, NBER Working Paper 17190, National Bureau of Economic Research, Cambridge, Mass., July 7, 2011. www.nber.org.
July 28, 2011
Valter Longo and colleagues proposed that a treatment used to prolong life in some laboratory organisms could offer protection against the negative effects of chemotherapy. That treatment is fasting, a special type of dietary restriction. Dietary restriction provides adequate nutrition at lower-than-average calories, either through special daily meals or intermittent fasting.
In some of the earlier studies of dietary restriction in animal models, researchers measured resistance to stress as a way of predicting potential impact on lifespan and health. Successful resistance to short-term stress caused by reduction in calories typically correlates with longer life and better health. Researchers have also found in some models that fasting for relatively short periods of time – or months of dietary restriction – actually enhanced normal cells’ resistance to stress, but did not have an effect on cancer cells.
Based on these observations, Longo and colleagues hypothesized that they could use this “differential stress resistance” induced by fasting to reduce chemotherapy-related stress on normal cells, without jeopardizing the treatment’s efficacy for killing cancerous cells. Initial results in mice were encouraging: the mice survived and the chemotherapy was still effective. A subsequent but still very preliminary clinical study showed that patients who fasted in conjunction with chemotherapy reported fewer side-effects without loss of efficacy. The clinical study has been expanded to an early phase clinical trial.
Raffaghello L, et al. Fasting and differential chemotherapy protection in patients. Cell Cycle 2010 9: 4474 – 4476.
Lee C, Longo VD. Fasting vs. dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene 2011 30: 3305 – 3316.
November 17, 2011
Certain behaviors and exposure to environmental elements can have a lasting impact on gene expression by modifying chromatin at both the DNA and protein levels. These modifications comprise the field of epigenetics. Because older people have literally a lifetime of exposure to the environment, it is likely that epigenetics might play a crucial role in aging. Yet, studies of the epigenetics of aging are just in their infancy.
Researchers have found that reducing a certain epigenetic modification of proteins associated with DNA in C. elegans (a type of round worm) leads to a longer lifespan. In the November 17, 2011, issue of Nature, A. Brunet’s group at Stanford University reports that lifespan extension (resulting from the reduction of this particular epigenetic modification) is inheritable for three generations. Breeding the worms that had the extended lifespan with wild-type worms resulted in offspring that had a wild-type genome; but, surprisingly, the offspring also lived longer than normal, wild-type worms. Offspring of the second generation of worms also had a longer lifespan, as did the generation after that. The inheritance of longer life did eventually subside after four generations.
It is too early to apply this finding to human aging, but the work reveals the possibility that good (or bad) habits can have a lasting effect not only on health and lifespan, but possibly on the health and lifespan of succeeding generations. More research is needed to determine the molecular mechanisms, and to establish whether the findings can be applied to more complex organisms.
Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature. 2011 Nov 17;479(7373):302-3.
December 6, 2011
The RAND Survey Meta Data Repository provides researchers with information on survey content from the international collection of longitudinal aging studies harmonized to the U.S. Health and Retirement Study. It includes a digital library of survey questions, a search engine for finding comparable questions across the surveys, and a set of identically defined variables for cross-country analysis for over ten studies (and growing). For more information, please visit the Mega Meta homepage.