• March 11, 2008

    A team led by researchers from the National Institute on Aging’s (NIA's) Laboratory of Neurogenetics conducted a genome-wide association study using genotype and transcriptome* expression arrays to study gene expression in the human brain. Working with brain tissue from 193 people age 65 and older who died free from neurological disease, the scientists found that 58 percent of more than 24,000 measured transcripts were expressed in the brain in at least 5 percent of the samples; of those transcripts, 21 percent had profiles suggesting that their expression was under genetic influence. By counting the number of transcripts, researchers may be able to determine what genes are active, or expressed, in brain cells and how genetic variations may contribute to a disease. Made possible through tissue donated by NIA-funded Alzheimer’s Disease Centers, this highly collaborative effort has made the database and most of the DNA samples accessible online to enable future studies regarding risk for common neurological diseases and which areas of the genome play a role. The research was published in Nature Genetics.

    *The transcriptome is a collection of all the gene transcripts found in a given cell. Transcripts, or messenger RNA (mRNA) molecules, deliver instructions for making proteins. By analyzing the transcriptome, scientists can learn when and where a gene is turned on or off in various types of cells and tissues.


    Myers, A., et al. (2007). A survey of genetic human cortical gene expression. Nat Genet. 2007 Dec;39(12):1494-9. Epub 2007 Nov 4.

  • March 11, 2008

    Cognitively normal people with a maternal family history of Alzheimer’s disease (AD) show reductions in their cerebral glucose metabolism in the same brain areas as those seen in people who have been diagnosed with AD, according to an National Institute on Aging-funded study by researchers at the New York University School of Medicine. These findings, published in the Proceedings of the National Academy of Sciences, are based on clinical, neuropsychological, and positron emission tomography (PET) examinations of 49 cognitively normal study participants age 50 to 80 who had a parental family history of AD. The researchers suggest that these findings, with further study, may improve understanding of preclinical changes related to AD.


    Mosconi, L. et al. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci USA. 2007 Nov 27;104(48):19067-72. Epub 2007 Nov 14.

  • March 17, 2009

    Research has shown that hypertension (high blood pressure), a common condition in older adults, affects cardiovascular function and, by extension, increases the risk of cerebrovascular disease. While previous studies have identified hypertension as a risk factor for cognitive decline and dementia, a new NIA-funded study was the first to use a brain imaging technology called continuous arterial spin-labeled magnetic resonance imaging (CASL-MRI) to look at the effect of hypertension on cognitively normal people.

    Researchers at the University of Pittsburgh School of Medicine studied 41 cognitively normal elderly people, 19 with hypertension and 22 without it, to compare regional cerebral blood flow (rCBF). The study participants, who ranged in age from 75 to 92, had noninvasive CASL-MRI, which measured rCBF rates over the entire brain. All of the individuals with hypertension controlled their blood pressure with medication.

    The CASL-MRI results showed that the people with hypertension had reduced cerebral blood flow in many subcortical regions of the brain, including the bilateral putamen, globus pallidus, and left hippocampus, as well as in the limbic and paralimbic structures. These results are consistent with those of previous studies that used other imaging methods.

    The authors suggest that, with further development, CASL-MRI might be used to predict dementia by identifying patterns of blood flow in the brains of hypertensive, cognitively healthy individuals and that better blood pressure control may help reduce the risk of AD.


    Weiying, Dai, et al. Abnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension. Stroke. 2008. 39:349-54.

  • March 17, 2009

    People with a large waist circumference have a higher risk of mortality, even if they have a normal body mass index (BMI—a ratio of weight to height), finds a recent study supported in part by the NIA. The results suggest that waist circumference should be considered as a health risk factor independent of BMI, according to Dr. Annemarie Koster and co-authors in the American Journal of Epidemiology.

    The researchers analyzed demographic and health data on 245,533 participants (154,776 men and 90,757 women) ages 51 to 72, drawn from the NIH–AARP Diet and Health Study. Defining a large waist circumference as more than 102 cm for men and 88 or more cm for women, they looked at the combined effects of BMI and waist circumference on time to death during 9 years (1996–2005).

    Individuals with a large waist circumference had a 20 percent higher mortality risk than those with a normal waist circumference, after adjusting for BMI, the investigators found. This higher risk existed in people with and without prevalent disease, in smokers and nonsmokers, and to varying degrees across racial and ethnic groups. In addition, among participants with a normal BMI, those with a large waist circumference had a 20 percent higher risk of death than those with a normal waist circumference.


    Koster A., et al. Waist circumference and mortality. Am J Epidemiol. 2008. 167:1465-75.

  • March 17, 2009

    The implementation of Medicare Part D—the prescription drug benefit—provided Americans aged 65 and over the opportunity to enroll for Medicare coverage of prescription drugs. Following the first year of the program, two teams of NIA-funded researchers analyzed aspects of this coverage to see how the program is affecting use of medications and how well older people understand the features of their Part D coverage.

    The results appeared in the April 23/30, 2008, issue of the Journal of the American Medical Association. The first study, by Dr. Jeanne Madden of Harvard Medical School in Boston and colleagues, examined cost-related medication nonadherence and spending on basic needs. The researchers found that the prevalence of cost-related medication nonadherence decreased from 14.1 percent in 2005 to 11.5 percent in 2006, following implementation of Medicare Part D. The prevalence of spending less on basic needs to afford medications was 11.1 percent in 2005 and 7.6 percent in 2006. Cost-related medication nonadherence was strongly associated with disabled status, poorer self-reported health, higher numbers of morbidities, and lower income, both before and after implementation of Part D.

    A second study, by Dr. John Hsu of the Center for Health Policy Studies of the Kaiser Permanente Medical Care Program in Oakland, CA, and colleagues, looked at beneficiaries’ knowledge of the coverage gaps in their Part D benefits and their response to drug costs when they reached the coverage gap. Among beneficiaries in a Medicare Advantage prescription plan, only 40 percent of beneficiaries surveyed said they knew that their plan included a coverage gap. Approximately 36 percent of these beneficiaries reported taking measures to control spending on prescriptions. Limited knowledge of coverage gaps was associated with more reports of financial burden. Seniors with worse knowledge of their Part D benefits were less likely to switch to lower cost medications and more likely to report reducing consumption of basic necessities, like food.

    “The study shows that many seniors have trouble understanding these benefits, and that this poor knowledge limits their ability to manage their medication needs and costs,” commented Dr. Hsu.


    Madden, J.M., et al.Cost-related medication nonadherence and spending on basic needs following Medicare Part D. JAMA. 2008. 299(16):1922–28

    Hsu, J., et al. Medicare beneficiaries’ knowledge of Part D prescription drug program benefits and responses to drug costs. JAMA. 2008. 299(16):1929–36.

  • March 17, 2009

    As they age, dogs, like people, can accumulate beta-amyloid (Aβ) plaques, sticky protein deposits in the brain that are a signature sign of Alzheimer’s disease (AD). In a recent NIA-funded study, immunization prevented these deposits and cleared preexisting ones in older dogs’ brains but yielded only limited cognitive improvement and functional benefit.

    Following up on studies in mice that linked immunization and reduced Aβ deposits, researchers studied a similar regimen in 20 8- to 12-year-old beagles. Nine dogs were given 25 injections of fibrillar Aβ1-42 and aluminum salt over a 2-year period (provided to boost the immune response). The control group of 11 dogs received either aluminum salt only or saline only. All of the animals were trained and regularly tested on several learning and memory tasks to assess changes in cognitive function.

    The researchers, led by Dr. Elizabeth Head of the University of California, Irvine, found no significant difference in cognition between the immunized dogs and the control groups, as shown by their performance on tasks measuring spatial attention, complex learning, and other aspects of cognition. The only exception was reversal learning, in which positive and negative stimuli are reversed, for which the immunized dogs showed less decline than the control-group dogs.

    Overall, there was a significant reduction in Aβ plaques in the immunized dogs’ brains, especially in the prefrontal cortex, seen at the end of the study. Smaller reductions in non-plaque (unassembled) Aβ were observed. Importantly, this unassembled form of Aβ may be most toxic to neurons and their synapses. The authors note that reducing preexisting plaques does not restore neuronal and cognitive function in dogs, as it has in aged mice. The canine results are consistent with vaccine studies in people with AD.


    Head, E., et al. A two-year study with fibrillar β-amyloid (Aβ) immunization in aged canines: Effects on cognitive function and brain Aβ. J Neurosci. 2008. 28(14):3555–66.

  • March 17, 2009

    Cognitive impairment in people with mild to moderate Alzheimer’s disease (AD) can diminish their capacity to provide informed consent for clinical trials, presenting ethical challenges for researchers. A semistructured interview can help determine which people are capable of giving their own informed consent, according to an NIA-supported study in the American Journal of Geriatric Psychiatry.

    The MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR), an interview tool that assesses 4 decision-making abilities—choice, understanding, appreciation, and reasoning—was administered to 59 people with mild to moderate AD, who were participating in a 13-site clinical trial. Researchers, led by Dr. Jason Karlawish of the University of Pennsylvania School of Medicine in Philadelphia, adapted the interview procedure by allowing individuals to keep a summary of the trial as they answered questions. Three psychiatrists independently reviewed the MacCAT-CR interviews and decided the strength of each subject’s capacity to give informed consent.

    The researchers found that MacCAT-CR scores, specifically the subscores for understanding, had the best ability to discriminate which subjects were able to provide informed consent. Nearly half of the study group (47 percent) was judged not capable of providing their own consent. However, the authors note, this proportion could vary depending on the risk of the study and the techniques interviewers use to administer the MacCAT-CR. They caution other investigators against using this tool alone to decide which people with AD are capable of providing informed consent, but to use its results “as evidence to guide what is ultimately an ethical judgment.”


    Karlawish, J., et al. Interpreting the clinical significance of capacity scores for informed consent in Alzheimer disease clinical trials. Am J Geriatr Psychiatry. 2008. 16(7):568-74. Epub 2008 June 12.

  • March 17, 2009

    Researchers at Princeton University in New Jersey and Stony Brook University in New York used a novel method to assess the percentage of people experiencing pain and its severity at randomly selected times in a representative sample of U.S. residents. According to results published in the May 3, 2008, Lancet, more than a quarter of American men and women report feeling pain at any point in time, and those with lower incomes and less education spent more time in pain and had higher than average pain.

    Collecting diary information through a community-based telephone survey, Drs. Alan Krueger and Arthur Stone found that 29 percent of men and 27 percent of women said they felt some pain at sampled times. People with lower incomes or less education spent a higher proportion of time in pain and reported feeling more severe pain than those with higher incomes or more education. The average pain rating increased with age, although it reached a temporary plateau between the ages of 45 and 75 before rising again above age 75. Information was not collected on the cause, location, treatment, or duration of the pain. Medical conditions that might have caused the pain were not identified.

    An important aspect of this NIA-funded study was the measurement of pain during specific random periods of time rather than the global assessment typically used in population studies. This approach allowed researchers to study how pain affected activities of daily living in particular segments of the sample population.


    Krueger, A.B., and Stone, A.A. Assessment of pain: a community-based diary survey in the USA. Lancet. 2008 May 3. 371:1519–25.

  • March 17, 2009

    Training clinical staff in fall-prevention practices and strategies can help reduce serious falls and the need for related medical care among elderly people, suggests a new study, funded in part by the NIA.

    Research has shown that falls—a common cause of injuries, hospitalization, and functional decline among older adults—can be prevented through multifaceted programs addressing multiple risk factors for falls. But known prevention strategies rarely transfer from academic study to clinical practice, and researchers from the Yale School of Medicine in New Haven, CT, looked at whether interventions educating a variety of clinicians about risk factors for falls would help reduce falls in people age 70 and older.

    Working with the Connecticut Collaboration for Fall Prevention, the research team led by Dr. Mary E. Tinetti encouraged clinicians (including primary-care doctors, physical therapists, and advanced practice nurses) and facilities (such as home health care agencies and hospitals) in the Hartford, CT, area to incorporate proven fall-prevention techniques into their practices, providing clinicians with training materials and teaching them how to educate seniors about fall prevention.

    After 2 years of evaluation, the researchers found the rate of serious fall-related injuries, such as hip fractures and head injuries, was 9 percent lower in the intervention area than in a demographically similar usual-care area in southern Connecticut. Similarly, the rate of fall-related use of medical services was 11 percent lower in the intervention area than in the usual-care area. Data came from a Connecticut Hospital Association database of information on all state residents who receive care in an emergency department or hospital.

    The authors could not say which particular intervention or which group of clinicians accounted for the differences between the two geographic areas. However, they suggest that much discomfort, disability, and health care spending due to falls by older people could be averted by disseminating information about fall prevention to clinicians and encouraging them to adopt changes in clinical practice.


    Tinnetti, M.E., et al. Effect of dissemination of evidence in reducing injuries from falls. N Engl J Med. 2008 July 17. 359:252-61.


  • May 12, 2009

    Researchers at the Pennington Biomedical Research Center in Baton Rouge, LA, have shown that when people significantly reduce their calorie intake, they undergo a metabolic adaptation that results in a slower metabolic rate. The slower metabolic rate results in a behavioral adaptation in which individuals become less physically active.

    The researchers examined data from 48 overweight people who followed 1 of 4 diet regimens for 6 months: a 25-percent calorie restriction (CR) diet, a low-calorie diet, a 12.5-percent CR diet plus 12.5-percent aerobic exercise program, or a normal diet. While the first three groups lost weight, after 6 months, the CR and low-calorie diet groups showed a reduction in their basal metabolic rate, accompanied by reduced physical activity. The CR plus physical activity group also lost weight but did not undergo a metabolic adaptation.

    This is the first study to measure metabolic rate and energy expenditure precisely through the use of doubly labeled water and indirect calorimetry. The study also shows that long-term calorie reduction without increased exercise can result in a lower metabolic rate. The researchers note that the data “suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.”


    Redman, L.M., et al. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS ONE. 2009. 4(2):e4377.