• June 15, 2010

    A recent study examining predictors of participant dropout in a clinical trial of treatments for mild cognitive impairment (MCI) has found that participants recruited by NIA-funded Alzheimer's Disease Centers (ADCs) and university-affiliated sites have dramatically lower dropout rates than do those recruited by commercial sites. The authors of the study, including researchers in ADCs at the University of California, San Diego, and the Mayo Clinic, suggest that superior participant retention rates may translate into greater statistical power and validity of clinical trial results.

    A high number of dropouts during a trial can weaken the statistical power of a trial and make it more difficult to detect an effect. In addition, a high number of dropouts may bias results, because participants that drop out may be different (e.g., they may be sicker, etc.) from those who complete the trial.

    The Edland, et al., study identified several demographic parameters that, in addition to the trial site, predict a higher dropout rate. Some of these include marital status, education, and race/ethnicity. For example, lower education and non-white race were associated with higher dropout. The authors speculate that retention efforts targeting the identified subgroups may improve the validity and power of future trials.

    The authors offer several possible causes for the differences in subject retention between ADCs and university-affiliated trial sites compared to commercial sites. The authors note that commercial sites tend to recruit more subjects through advertising. ADCs and university-affiliated sites also recruit through advertising, but they recruit many participants from their clinic populations. Longstanding relationships among clinic staff and participants may improve retention. Moreover, people who respond to advertising may be more focused on receiving the active drug or treatment and be more likely to drop out if they believe they are receiving placebo, think the drug is not working, or it causes unwelcome side effects.

    Edland, S.D., et al. NIA-funded Alzheimer Centers are more efficient than commercial clinical recruitment sites for conducting secondary prevention trials of dementia. Alzheimer's Disease and Associated Disorders. 2010. 24(2):159-64.

  • March 11, 2008

    Physical conditioning helps maintain older adults’ driving performance, decreasing on-road errors by more than one-third, suggests National Institute on Aging-sponsored research published in the Journal of General Internal Medicine.

    The randomized, controlled trial included 178 drivers age 70 and older who were driving at least once a week and had physical but not substantial visual or cognitive impairments when recruited. The intervention group received 12 weekly visits from a physical therapist who led them through a graduated exercise program to improve flexibility, coordination, and speed of movement relevant to driving and asked them to do the exercises for 15 minutes each day. The control group received monthly in-home education about home safety, fall prevention, and vehicle care.

    From baseline to 3 months, overall on-road driving performance remained unchanged among those who took part in the physical conditioning program, while the control group’s performance declined. The investigators assessed the number of “critical errors”—not paying attention, changing lanes without looking, and disobeying traffic signs or signals—made during the on-road driving evaluation. They found that the conditioning group committed 37 percent fewer critical errors, and had fewer falls than the control group over the 3 months.


    Marottoli, R.A., et al. A randomized trial of a physical conditioning program to enhance the driving performance of older persons. J Gen Intern Med. 2007 May;22(5):590-7.

  • March 11, 2008

    Patients with mild cognitive impairment (MCI) may, in addition to their cognitive impairment, have functional limitations that diminish their ability to make decisions about medical treatment. Researchers at the National Institute on Aging-funded Alzheimer’s Disease Research Center at the University of Alabama at Birmingham used the Capacity to Consent to Treatment Instrument (CCTI) and a comprehensive neuropsychological battery to assess the medical decision-making abilities of 56 healthy controls, 60 people with MCI, and 31 people with mild Alzheimer’s disease. The CCTI consists of two clinical vignettes presenting a hypothetical medical problem and symptoms and two treatment alternatives. Consent capacity scores were assigned for each of four consent standards.

    The MCI group scored significantly lower than the control group on measures for appreciating the consequences of a treatment choice (6.82 and 7.55 out of 8 points, respectively); reasoning for making a particular treatment choice (7.48 and 9.52 out of 12 points, respectively); and understanding the treatment situation, treatment choices, and risks/benefits (49.78 and 62.1 out of 78 points, respectively). The study also showed differences within the MCI group. Some of those with MCI performed well on even the most stringent consent standard—understanding the treatment situation, treatment choices, and risks/benefits—suggesting that they still had the capacity to make medical decisions.

    Based on these findings, published in Neurology, the researchers suggest that clinicians and researchers repeat key points, use simple language, and ask targeted questions when seeking informed consent for treatment from people with MCI.


    Okonkwo, O., et al. Medical decision-making capacity in patients with mild cognitive impairment. Neurology. 2007 Oct 9;69(15):1528-35.

  • March 11, 2008

    Limited time, limited reimbursement, and other health care barriers may lead to challenges when treating dementia patients, according to a study by the NIA-funded Alzheimer’s Disease Research Center at the University of California, San Francisco. These findings, published in the November 2007 issue of the Journal of General Internal Medicine, are based on open-ended interviews with 40 primary care physicians in Northern California. Recurring themes arising in at least 25 percent of the interviews included insufficient time, difficulty accessing and communicating with specialists, low reimbursement for certain services, and poor connections with community social service agencies.

    The findings suggest that practice constraints may lead to delayed detection of behavioral problems, reactive rather than proactive dementia management, and reliance on pharmacological rather than psychosocial approaches to care. The researchers conclude that more effective educational interventions for families and physicians and structural practice changes are needed to better meet the needs of people with dementia and their families.


    Hinton, L., et al. Practice constraints, behavioral problems, and dementia care: Primary care physicians’ perspectives. J Gen Intern Med. 2007 Nov;22(11):1487-92. Epub 2007 Sep 7.

  • 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.