• June 15, 2010

    Allopregnanolone, a metabolite of the hormone progesterone that is made in the central nervous system, reversed neurological decline and improved performance on memory tests in 3-month-old mice with characteristics of Alzheimer's disease, a recent study showed. Allopregnanolone can increase the number of neural progenitor cells of mice and humans in vitro. In this study, led by researchers at the University of California, Los Angeles, the same molecule was given in vivo to triple transgenic Alzheimer's disease mice and to normal mice to test its effect on learning and memory. Allopregnanolone was found to regenerate nerve cells significantly in a part of the hippocampus—a region of the brain important to memory—in the transgenic mice but not in the normal mice. The Alzheimer's mice not only improved their performance on a trace eye-blink conditioning test of learning and memory, but performed as well as did the normal mice.

    Allopregnanolone can reverse cognitive deficits in an Alzheimer's mouse model, perhaps by helping certain nerve cells proliferate and thrive, the authors concluded. The findings, they say, suggest further investigation of allopregnanolone for its therapeutic potential in Alzheimer's disease.

    Wang, J.M., et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences USA. 2010. 107(14):6498-503. (PDF, 690K)

  • June 15, 2010

    Older adults with strong muscles are at lower risk of developing Alzheimer's disease and mild cognitive impairment than their weaker peers, researchers report in Archives of Neurology. The study builds on previous research showing a link between grip strength and Alzheimer's risk.

    In this study, researchers at the Rush University Alzheimer's Disease Center in Chicago measured a wide range of cognitive skills and muscle strength throughout the body in 970 participants with an average age of 80 years. During nearly 4 years of follow-up, 138 people developed Alzheimer's disease. After adjusting for age and other variables, the researchers found that the strongest 10 percent of participants had a 61 percent lower risk of developing Alzheimer's, compared with the weakest 10 percent of study participants. Muscle strength and mild cognitive impairment, a condition that often precedes Alzheimer's, were similarly but less closely linked. Stronger muscles were also associated with a slower rate of cognitive decline.

    The authors surmise that a common underlying disease process could account for the association between muscle weakness and declining cognition. Replication of the results in a population-based study is important, they add.

    Boyle, P.A., et al. Association of muscle strength with the risk of Alzheimer's disease and the rate of cognitive decline in community-dwelling older persons. Archives of Neurology. 2009. 66(11):1339-44.

  • June 15, 2010

    Cognitive fluctuations are common in people who have dementia with Lewy bodies, but they have rarely been assessed in people with Alzheimer's disease. According to one new study, such fluctuations do occur with Alzheimer's disease and are correlated with impaired performance on neuropsychological tests.

    The study found that older people with “cognitive fluctuations”—spontaneous changes in cognition, attention, and arousal—are more likely than people without these fluctuations to have Alzheimer's disease, according to researchers at the Alzheimer's Disease Research Center at Washington University, St. Louis. Of 511 subjects (average age, 78 years) in this NIA-funded study, 12 percent had cognitive fluctuations, defined as having three or four of the following symptoms: often feeling drowsy or lethargic during the day despite a good night's sleep, sleeping 2 or more hours before 7 p.m., having disorganized or unclear thoughts at times, and staring into space for long periods. Subjects with these symptoms were 4.6 times more likely to have Alzheimer's than were those without them, with disorganized, illogical thinking having the strongest correlation with dementia.

    These fluctuations may be possible new symptoms to be considered in the diagnosis of Alzheimer's disease, the study authors conclude.

    Escandon, A., et al. Effect of cognitive fluctuation on neuropsychological performance in aging and dementia. Neurology. 2010. 74:210-17.

  • June 15, 2010

    The cognitive health of older adults with “subjective cognitive impairment” (SCI) declined faster and further than that of people without SCI over a period of years, a recent study found. The study suggests that very early, subtle changes in memory in people who test as cognitively normal might predict more serious types of impairment.

    In SCI, people complain of memory problems but score in the normal range on tests of cognition. Complaints of cognitive impairment are commonly heard from older adults. In this NIA-supported study, 213 cognitively healthy subjects at least 40 years old—166 with SCI and 47 without—were followed for an average of 7 years after taking a series of baseline neuropsychological tests. Over that time, 54 percent of people with SCI progressed to mild cognitive impairment or probable dementia, compared with only 15 percent of people without SCI. The people with SCI declined faster, too, with an average time to decline of 5.3 years vs. 8.8 years for those without SCI.

    The study investigators, Dr. Barry Reisberg of the New York University School of Medicine and colleagues, suggest further studies be done of SCI in broader at-risk populations to assess the possibility of using SCI to identify individuals for prevention studies.


    Reisberg, B., et al. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimer's & Dementia. 2010. 6(1):11-24.

  • June 15, 2010

    African-American family members and other informants are less likely than are their white counterparts to report mild cognitive impairment in people who are cognitively impaired but not demented (CIND), NIA-funded research shows. The finding suggests that cultural differences may influence informant reports of cognitive impairment in non-demented people.

    The analysis included 645 older African-American and white participants in the Aging, Demographics, and Memory Study, a subset of the NIA-funded Health and Retirement Study. Researchers compared results of both direct testing of participants and informant reports of participant cognition with clinical diagnoses of cognitive impairment and dementia. Informants completed the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)—a widely used measure of cognitive decline, while participants were given clinical diagnoses of normal cognition, CIND, or dementia by an expert panel.

    Informant reports of higher cognitive decline, as measured by IQCODE scores, were associated with increased odds of dementia in both African Americans and whites. However, higher IQCODE scores were associated with increased odds of CIND diagnosis among whites but not among African Americans. For both African Americans and whites, a higher total score on another test, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) measure, was associated with lower odds of CIND and dementia.

    The results suggest that African-American informants are less inclined than whites are to report mild cognitive changes, the authors explain. More comparative research is needed to establish the cultural validity of measures used to diagnose cognitive impairment, the researchers state.


    Potter, G.G., et al. Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites. Alzheimer's & Dementia. 2009. 5:445-53.

  • 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.