Announcements

  • April 15, 2009

    People with increased levels of tau protein in their CSF develop late-onset AD at earlier ages than do others with the disease, according to a study by researchers at the Washington University School of Medicine in St. Louis. The levels of this protein in CSF may provide a potential biomarker to identify people who may develop AD sooner than others do. The levels of both beta-amyloid and tau—two proteins whose abnormalities characterize AD—in CSF vary widely in individuals with the disease.

    The investigators used genotyping to pinpoint the association between MAPT, the gene that encodes tau, and AD. They found four genetic variants of MAPT that were associated with higher levels of tau, but the higher tau levels were found only in the presence of beta-amyloid deposits. The researchers also confirmed that the genetic variants of MAPT influenced the age at onset of AD clinical symptoms but had no effect on the overall risk of developing AD.

    The results indicate that beta-amyloid deposition leads to MAPT gene expression, which in turn raises tau levels and increases early neurodegeneration in late-onset AD.

    Reference:

    Kauwe, J.S., et al. Variation of MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. Proc Natl Acad Sci USA. 2008 Jun 10. 105(23):8050-54.

  • April 15, 2009

    Previous studies have suggested that frailty, a common but poorly understood condition in older people, may predict the development of dementia. In this study, Rush University researchers examined 165 physically frail older adults before and after their deaths to investigate this connection. First, participants' frailty was evaluated by measuring their grip strength, timed walk, body composition, and fatigue. After death (at a mean age of 88.1 years), their brains were autopsied for evidence of AD, cerebral infarcts, and Lewy body disease.

    Regression analyses controlling for age, chronic diseases, medications, and other factors showed an association between levels of frailty and of AD pathology but no association between frailty and cerebral infarcts or Lewy body disease. A higher level of AD pathology was associated with a higher level of frailty. The link was similar in people with and without dementia.

    The researchers speculate that AD pathology may contribute to frailty by affecting parts of the brain that control movement. Or, AD and frailty may share a common cause. "These different mechanisms are not mutually exclusive and underscore the need for further studies of the relationship between AD and frailty," they conclude.

    Reference:

    Buchman, A.S., et al. Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology. 2008. 71:499-504.

  • April 15, 2009

    Examination of people at risk for the rare familial form of AD may provide clues to how the disease develops in others—years before clinical symptoms appear, according to a recent study. The clues are levels of certain proteins found in plasma and cerebrospinal fluid (CSF), biomarkers that might be used to diagnose AD in its earliest preclinical stage.

    The research team, led by scientists at the University of California, Los Angeles, examined blood and CSF samples from 21 adults under age 50, most of whom had no symptoms of AD but were related to people with familial AD, a genetically inherited form of the disease. One of their biomarkers, elevated levels of plasma Aß42 (a type of beta-amyloid protein), also has been found in people with late-onset AD.

    The results confirmed and amplified what previous studies have shown: Pre-symptomatic people with the familial-AD mutation had higher levels of plasma Aß42, which declined as the disease progressed, as well as higher plasma Aß42/Aß40 ratios, than those in people without the mutation. People with the mutation had lower CSF Aß42/Aß40 ratios and higher levels of CSF tau and p-tau181 than people who did not carry the mutation. There was no significant difference between the two groups in plasma F2-isoprostane levels.

    Reference:

    Ringman, J.M., et al. Biochemical markers in persons with preclinical familial Alzheimer disease. Neurology. 2008 July. 71:85-92.

  • April 15, 2009

    Receiving a diagnosis of dementia does not prompt a strong negative reaction in most people and may even provide relief because it explains symptoms and makes patients feel less helpless, concludes a recent study.

    To gauge psychological reactions to a dementia diagnosis, researchers from Washington University in St. Louis conducted telephone interviews with patients a few days after they received a dementia diagnosis. Two tests were used: the Geriatric Depression Scale and the "State" version of the State-Trait Anxiety Inventory. Both patients and their companions took the tests. Baseline scores were obtained through comprehensive physical and neurological examinations. Of 90 study participants, 41 were diagnosed with very mild dementia, 21 with mild dementia, and 28 with no dementia.

    The researchers found no significant increase in depression in individuals or their companions, regardless of diagnostic outcome or dementia severity. The level of anxiety also did not increase—and decreased significantly in some cases.

    Reference:

    Carpenter, B.D., et al. Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment. J Am Geriatr Soc. 2008. 56:405-12.

    More information for health care professionals about communicating with older patients is provided in the NIA publication Talking With Your Older Patient: A Clinician's Handbook.

  • April 15, 2009

    A combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) can more accurately detect mild cognitive impairment (MCI) brain abnormalities in the early stages of their development than can either method used alone, a recent study finds. Early diagnosis of amnestic MCI is important because the condition is often a precursor to Alzheimer's disease (AD).

    The researchers, from the National Institute on Aging (NIA) and the University of Pennsylvania, examined MRI and PET images from 30 elderly participants in NIA's Baltimore Longitudinal Study of Aging to distinguish people with aMCI from people who were aging normally. They looked at spatial patterns of brain atrophy and reduced blood flow in dozens of regions of the brain.

    MRI data alone produced an 87 percent accuracy rate for aMCI diagnosis, and PET data alone produced a 50 percent accuracy rate. However, when the two were combined, researchers obtained a 90 to 100 percent accuracy rate—"an excellent diagnostic value" for this method.

    Reference:

    Fan Y., et al. Structural and functional biomarkers of prodromal Alzheimer's disease: a high-dimensional pattern classification study. Neuroimage. 2008. 41:277-85.

  • April 15, 2009

    The Rosalyn Carter Leadership in Caregiving Award is among the most prestigious awards in the caregiving field. This award, presented annually by the Rosalyn Carter Institute of Caregiving, recognizes programs that develop and implement innovative approaches to promote collaborations between community agencies and caregiving researchers that bridge the gap between science and practice.

    One of two 2008 awards recognizes the REACH VA program, implemented by the Veterans Health Administration (VHA) Geriatrics and Extended Care Unit in partnership with the Memphis VA Medical Center. REACH VA focuses on "education, safety for the patient, support for the caregiver, and skills building to help caregivers manage difficult patient behaviors and decrease their own stress." The goal of REACH VA is "to implement an effective intervention to decrease caregiver stress and improve the management of patient behaviors throughout the VHA system."

    REACH VA is the first national clinical translation of a proven dementia behavioral intervention, REACH II (Resources for Advancing Alzheimer's Caregiver Health). REACH II is a social and behavioral research effort funded by NIA and the National Institute of Nursing Research. The goal of REACH II is to translate the results of research in caregiver support into evidence-based community practices. REACH VA has made it possible to broadly implement the findings from the REACH II research project. Clinical staffs from VA Home-Based Primary Care programs in 36 cities and 19 states have volunteered to learn and deliver the intervention to caregivers of dementia patients.

    The second winner of the 2008 award is Minnesota's NYU Caregiver Intervention Project, designed and implemented by the Minnesota Board on Aging and the Alzheimer's Association Minnesota/North Dakota Chapter, in partnership with New York University's Dr. Mary Mittelman and Cynthia Epstein. The goals of the project are to develop and improve appropriate supportive services for people with Alzheimer's disease and to integrate these services into long-term care-, home-, and community-based systems. The project uses the care model developed by Dr. Mittelman and funded in part by NIA. In the journal Neurology, Dr. Mittelman and colleagues report that nursing home placement for patients with AD who received their care intervention was delayed a median of 557 days, due in large part to improvements in caregiver social support, learned responses to patient behavior problems, and symptoms of depression.

  • October 15, 2009

    A new “dementia risk index” can accurately predict which older adults will develop dementia within 6 years, according to a study in Neurology. Some of the factors that may predict dementia—age, poor performance on cognitive tests, and the apolipoprotein E ε4 gene—are well known. Others, such as ventricular enlargement, not drinking alcohol, and being underweight, are less well known. The tool could be developed for use in clinical and research settings to target prevention and treatment strategies for high-risk individuals.

    Researchers at the University of California, San Francisco, devised the index by studying 3,375 participants from the Cardiovascular Health Cognition Study, part of the larger Cardiovascular Health Study of people 65 and older. Of the participants, 14 percent developed dementia during the 6-year study. Fifty-six percent of participants with high scores on the 15-point index developed dementia, compared with 23 percent with mid-range scores and 4 percent with low scores.

    The study lays the groundwork for development of a shorter, simpler index that would be easier to use in a doctor’s office, yet have the same predictive accuracy, the researchers write.

    Reference:

    Barnes, D.E., et al. Predicting risk of dementia in older adults: the late-life dementia risk index. Neurology. 2009. Epub. May 13, 2009.

  • October 15, 2009

    An article in the Spring 2009 issue of Connections (Is a Big Belly Bad for the Brain? Examining Body Fat's Ties to Dementia) described research into links between obesity, Alzheimer’s disease, and other dementias. The article mentions studies that have found “both generalized and regional brain atrophy and changes in white matter in association with obesity." A recent 5-year study, partly funded by the NIA, amplifies earlier work, by showing that overweight or obese participants tended to have lower brain volumes in specific areas. To obtain these results, scientists at the University of Pittsburgh and the University of California, Los Angeles, applied sophisticated methods of computer analysis to high-resolution brain scans.

    This is the first time anyone has created brain maps showing a possible link between being overweight and brain degeneration in particular brain regions, according to senior investigator Dr. Paul M. Thompson. “The brains of obese people looked 16 years older than the brains of those who were lean, and the brains of overweight people looked 8 years older,” he said.

    Raji, C., et al. Brain structure and obesity. Human Brain Mapping (online ahead of print). August 6, 2009.

  • October 15, 2009

    Reduction of a protein in cerebrospinal fluid called brain-derived neurotrophic factor (BDNF) is associated with age-related cognitive decline, report scientists at the University of Washington School of Medicine in Seattle. The study confirms earlier research findings of low levels of BDNF in the cerebrospinal fluid of people with Alzheimer’s disease. Now, scientists have found reduced BDNF in older adults, including cognitively normal ones across the lifespan.

    The researchers compared BDNF levels in the cerebrospinal fluid of 128 cognitively normal people, 21 with Alzheimer’s, and 9 with mild cognitive impairment, who were given standard tests of memory and cognition. The scientists found that, as the normal participants aged, not only did their test scores fall, but also BDNF levels were lower.

    The findings suggest that reduced secretion of BDNF is associated with age-related cognitive decline in the absence of dementia or MCI and independent of the presence of the APOE e4 allele and the BDNF variant. The authors conclude that further studies are needed to validate their results. If these results are validated, scientists can look for ways to increase levels of BDNF to determine whether this restores cognition or slows its decline.

    Li, G., et al. Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects. PloS One. 2009. 4(5):e5424.

  • October 15, 2009

    An NIA-funded study at Columbia University Medical Center has found an association between a Mediterranean diet and a reduced risk of mild cognitive impairment (MCI). Previous studies have found an association of this diet with a reduced risk of Alzheimer’s disease. Many people with MCI ultimately develop Alzheimer’s. A Mediterranean diet includes vegetables, legumes, fruits, cereals, fish, and mono-unsaturated fats; mild to moderate alcohol use; and low intake of saturated fats, dairy products, meat, and poultry.

    The researchers recruited 1,393 cognitively normal participants and 482 participants with MCI. Subjects were divided into three groups, characterized by low, medium, and high adherence to a Mediterranean diet. After an average 4.3 years, 275 of the cognitively normal participants had developed MCI, and 106 of the participants with MCI had progressed to Alzheimer’s disease. The high-adherence groups had a 28 percent and 48 percent lower risk of developing MCI and progressing to Alzheimer’s, respectively, than those in the low-adherence group did. Those in the medium-adherence group had a 17 percent and 45 percent lower risk of MCI and Alzheimer’s, respectively, than did those in the low-adherence group.

    Researchers speculated that a Mediterranean diet may improve cholesterol and blood sugar levels and blood vessel health or reduce inflammation, all of which have been associated with MCI, but more research is needed to determine whether it has the effect suggested in this epidemiological study.

    Scarmeas, N., et al. Mediterranean diet and mild cognitive impairment. Arch Neurol. 2009. 66(2):216-25.

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