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ARRA Investments in Age-Related Cognitive Decline and Alzheimer’s Disease: Comparative Effectiveness Research

Public Health Burden
Some cognitive change is normal with advancing age. However, memory loss and other symptoms of cognitive decline can signal the onset of Alzheimer’s disease (AD), an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks of daily living. Estimates vary, but experts suggest that between 2.6 million and 5.1 million Americans aged 65 years and older may have AD, and these numbers are predicted to increase to 13.2 million by 2050 unless more effective ways to treat and prevent AD are found. In April 2010, the expert panel of the NIH State of the Science Conference on Preventing Alzheimer’s Disease and Cognitive Decline determined that there is currently insufficient scientific evidence to support use of any interventions to prevent age-related cognitive decline or AD.

Comparative Effectiveness Studies
Comparative effectiveness studies compare the clinical outcomes, effectiveness, and appropriateness of items, services, and procedures that are used to prevent, diagnose, or treat diseases, disorders, and other health conditions. Such studies can provide information on the relative strengths and weaknesses of various medical interventions and help clinicians and patients make treatment decisions. ARRA funds are being used to identify the most effective ways to delay or prevent the onset of age-related cognitive decline, diagnose AD, and manage AD’s symptoms.

Prevention of Age-Related Cognitive Decline and Alzheimer’s Disease
Several lifestyle interventions, including cognitive training and physical exercise, have been associated with a reduced risk of cognitive decline and/or AD in both animal and human studies. However, the effectiveness of such interventions has not been definitively established. ARRA-supported researchers are comparing the effectiveness of lifestyle interventions to prevent cognitive decline and AD.
  • Several studies compare cognitive training, physical exercise, or a combination of the two in cognitively normal elders. In one study, investigators are comparing the effects of physical training and training in “reasoning” on cognitive performance and brain structure and function in cognitively normal older adults.1 Other ARRA-supported researchers are developing and pilot testing a Web-based health coaching platform for delivering health interventions to elders in their homes; this will facilitate a larger clinical trial evaluating the effectiveness of various cognitive interventions delivered over longer periods of time with remote health coaching technology.2 Scientists are also comparing the effectiveness of a cognitive engagement intervention (quilting, digital photography, or both), a walking regimen, or a combination of the two on cognition and on blood flow to the brain, which may, when increased, enhance the effects of cognitive training.3
  • In 2002, NIH-supported researchers on the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study found that several cognitive training interventions, but particularly training in the domain of speed of processing (focusing on the ability to identify and locate visual information quickly), improved memory, concentration, and problem solving skills in healthy independent adults 65 years and older, and that these improvements persisted for several years after training ended. ARRA-funded researchers are extending and expanding these findings using an updated version of the speed of processing software that can be used on virtually any home computer without supervision. If shown to be at least as effective as the original, the new version of the software will be ready for widespread implementation to reduce and/or prevent the risk of disability driven by age-related cognitive decline.4
  • A study compares the effects of cognitive training, aerobic exercise training, and a combination intervention on cognitive outcomes and imaging biomarkers in older individuals who are at genetic risk for developing AD or have a family history of the disease.5
  • A study assesses the impact of exercise training, cognitive training, and a combination intervention on physical fitness, inflammatory and immunological biomarkers, and cognitive function among Hispanic and non-Hispanic older adults with mild cognitive impairment, often a precursor condition to AD.6
Diagnosing Alzheimer’s Disease
Identification of AD biomarkers in the blood and cerebrospinal fluid, along with the development of new imaging tools that allow visualization of AD’s characteristic pathology in the living brain, have improved our ability to diagnose the condition. However, optimal diagnostic methods remain to be determined. Investigators are:
  • Comparing genetic and imaging data from individuals with AD, then developing a “composite classifier” to determine whether composite data is more useful than either data source alone in diagnosing AD.7
  • Comparing brain imaging and blood biomarkers in diagnosing AD.8
Managing the Symptoms of Alzheimer’s Disease
  • Eating problems are common in persons with dementia. However, controversy exists about the effectiveness of feeding tubes, and hospitals vary in their rate of feeding tube use among patients with dementia. An ARRA-supported study will establish the effectiveness of feeding tubes and identify hospital characteristics and state policies that could account for the variation in feeding tube use.9
  • Investigators are validating and comparing measures of patient-reported outcomes in patients with AD or who are at risk. Results will facilitate future CER studies of interventions for AD and cognitive decline.10

  1. 1RC1AG035954-01 – Brain & Cognitive Changes After Reasoning or Physical Training in Cognitively Normal Seniors – Chapman, Sandra (TX)
  2. 1RC1AG036121-01 – Cognitive Interventions Delivered to Elders in the Home via Coaching Technology – Jimison, Holly Brugge (OR)
  3. 1RC1AG036003-01 – Impact of Exercise and Engagement on Cognition in Older Adults – Park, Denise (TX)
  4. 1RC1AG035546-01 – RCT of Two Speed of Processing Modes to Prevent Cognitive Decline in Older Adults – Wolinsky, Fredric (IA)
  5. 1RC1AG035775-01 – Neural Effects of Exercise, Cognitive, or Combined Training in AD At-Risk Elders – Rao, Stephen (OH)
  6. 1RC1AG035933-01 – Exercise versus Cognitive Interventions for Elders at Risk for Dementia – Loewenstein, David (FL)
  7. 1RC1AG035691 – Genetic, Genomic, and Imaging Biomarkers in Degenerative Dementia – Coppola, Giovanni (CA)
  8. 1RC1AG036208 – Comparative Effectiveness of Brain Imaging and Blood Biomarkers in Alzheimer’s Disease. Lazarov,Orly (IL)
  9. 1RC1AG036418-01—Effectiveness of Feeding Tubes among Persons with Advanced Cognitive Impairment – Teno, Joan (RI)
  10. 1RC4AG038825-01 – Assessing Early Alzheimer and At-Risk Groups with Patient-Reported Outcomes – Smyth, Kathleen (OH)

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