New Research Discoveries

Benefits of cognitive training can last 10 years in older adults


Jan. 16, 2014

by Eric Schoch

Exercises meant to boost mental sharpness can benefit older adults as many as 10 years after they received the cognitive training, researchers said Monday.

In a study published online by the Journal of the American Geriatrics Society, a multi-institutional team of researchers reported that older adults who had participated in the mental exercise programs reported less difficulty with everyday tasks of living than were those who had not participated, even after 10 years had passed.

The study, known as Advanced Cognitive Training for Independent and Vital Elderly, or ACTIVE, is the first to link such cognitive training to benefits in activities in everyday living and not just to mental skills related to the exercises, said Frederick W. Unverzagt, Ph.D., professor in the Department of Psychiatry at the IU School of Medicine and one of the ACTIVE study investigators.

“Previous data from this clinical trial demonstrated that the effects of the training lasted for five years,” said Richard J. Hodes, M.D., director of the National Institute on Aging. “Now, these longer term results indicate that particular types of cognitive training can provide a lasting benefit a decade later. They suggest that we should continue to pursue cognitive training as an intervention that might help maintain the mental abilities of older people so that they may remain independent and in the community.”

Dr. Unverzagt also discusses his research in a video on Vital Signs.

The study involved 2,832 people living independently in Detroit, Baltimore and western Maryland, Birmingham, Ala., Indianapolis, Boston and central Pennsylvania. The participants averaged 74 years old at the beginning of the study. About one-quarter of the participants were African-Americans, and about three-quarters were women.

The participants were divided randomly into groups receiving either memory training, reasoning training or speed training. A fourth -- control -- group received no training. Meeting in small groups, the participants had 10 training sessions of 60 to 75 minutes each over a period of five to six weeks. Some participants received "booster" training one and three years after the initial sessions.

Memory training involved improving abilities to recall texts and lists. Reasoning training included solving problems that involved patterns. Speed training, conducted on touch screen computers, was designed to increase speed in identifying information in different screen locations. The types of training were selected because they appeared in previous testing to be applicable to such daily activities as using the phone, tracking medication use and taking care of finances.

After 10 years, participants in each of the training groups reported less difficulty in conducting activities of daily living than those in the control groups. Participants in all three treatment groups saw immediate improvements in the cognitive ability that was trained compared to participants in the control group who received no training. This cognitive improvement was maintained through 5 years for all three treatments and through 10 years for the participants who received reasoning and speed training. 

"The durability of this effect was remarkable," Dr. Unverzagt said.

Dr. Unverzagt noted that overall, the training sessions produced clear but modest benefits, suggesting it would be worthwhile to study the potential benefits of combining cognitive training with other lifestyle and health interventions as exercise and improved diet.

Other researchers involved in the study were Karlene Ball, Ph.D., Department of Psychology, University of Alabama at Birmingham; Richard N. Jones, Sc.D., Social and Health Policy Research, Hebrew SeniorLife; Jonathan W. King, Ph.D., Division of Social and Behavioral Research, National Institute on Aging; Michael Marsiske, Ph.D., Institute on Aging and Department of Clinical and Health Psychology, University of Florida; John N. Morris, Ph.D., Social and Health Policy Research, Hebrew SeniorLife; George W. Rebok, Ph.D., Department of Mental Health and Center on Aging and Health, Johns Hopkins University; Sharon L. Tennstedt, Ph.D., New England Research Institutes and Sherry L. Willis, Ph.D., Department of Psychiatry and Behavioral Sciences, University of Washington; the ACTIVE Study Group.

The study was supported by grant numbers U01NR04507, U01NR04508, U01AG14260, U01AG14282, U01AG14263, U01AG14289, and U01AG14276 from the National Institute on Aging and the National Institute for Nursing Research of the National Institutes of Health.

Genome-wide imaging study identifies new gene associated with Alzheimer’s plaques

February 20, 2013

INDIANAPOLIS -- A study combining genetic data with brain imaging, designed to identify genes associated with the amyloid plaque deposits found in Alzheimer’s disease patients, has not only identified the APOE gene -- long associated with development of Alzheimer’s -- but has uncovered an association with a second gene, called BCHE.

A national research team, led by scientists at the Indiana University School of Medicine, reported the results of the study in an article in Molecular Psychiatry posted online Tuesday. The study is believed to be the first genome-wide association study of plaque deposits using a specialized PET scan tracer that binds to amyloid.

The research also is believed to be the first to implicate variations in the BCHE gene in plaque deposits visualized in living individuals who have been diagnosed with Alzheimer’s disease or are at-risk for developing the disease. The enzyme coded by the BCHE gene has previously been studied in post-mortem brain tissue and is known to be found in plaques.

“The findings could recharge research efforts studying the molecular pathways contributing to amyloid deposits in the brain as Alzheimer’s disease develops and affects learning and memory,” said Vijay K. Ramanan, the paper’s first author and an M.D./Ph.D. student at the IU School of Medicine.

The BCHE gene finding “brings together two of the major hypotheses about the development of Alzheimer’s disease,” said Andrew J. Saykin, Psy.D., Raymond C. Beeler Professor of Radiology and Imaging Sciences at IU and principal investigator for the genetics core of the Alzheimer’s Disease Neuroimaging Initiative.

Scientists have long pointed to the loss of an important brain neurotransmitter, acetylcholine, which is depleted early in the development of the disease, as a key aspect of the loss of memory related neurons. The BCHE gene is responsible for an enzyme that breaks down acetylcholine in the brain. The other major Alzheimer’s hypothesis holds that the development of the amyloid plaques is the primary cause of the disease’s debilitating symptoms. As it turns out, the enzyme for which the BCHE gene codes is also found in significant quantities in those plaques.

“This study is connecting two of the biggest Alzheimer’s dots,” said Dr. Saykin, director of the Indiana Alzheimer Disease Center and the IU Center for Neuroimaging at the IU Health Neuroscience Center.

“The finding that BCHE gene variant predicts the extent of plaque deposit in PET scans among people at risk for Alzheimer’s disease is likely to reinvigorate research into drugs that could modify the disease by affecting the BCHE enzyme or its metabolic pathway,” he said. Some existing drugs inhibit this enzyme, but it is unclear whether this influences plaque deposits.

Overall, the results appear to offer scientists new potential targets for drugs to slow, reverse or even prevent the disease. Alzheimer’s disease affects an estimated 5.4 million Americans and has proven resistant to treatments that do more than temporarily slow the worsening of symptoms.

Amyloid plaque deposits build up abnormally in the brains of Alzheimer’s patients and are believed to play an important role in the memory loss and other problems that plague patients.

The study makes use of an imaging agent, florbetapir, now approved for use by the U.S. Food and Drug Administration, that allows physicians to see the level of plaque buildup in a patient’s brain, something that previously could be determined only with an autopsy.

In a genome-wide association study, researchers evaluate alternate versions of many genes to determine whether particular genetic variants are associated with a particular trait -- in this case, the amounts of amyloid plaque deposits that the PET scans revealed in the brains of study participants.

Using the imaging agent that enables detection of the plaques in the brain, the researchers conducted PET scans of 555 participants in the Alzheimer’s Disease Neuroimaging Initiative, a long-term public-private research project that includes people at risk for Alzheimer’s disease and patients who have been diagnosed with the disease as well as participants with no symptoms.

With sophisticated statistical analyses, the imaging data was combined with analyses of DNA collected from the 555 participants to determine whether particular gene variants were found more often among patients with higher levels of plaque deposits.

The analysis found that a variant in BCHE was significantly associated with the levels of plaque deposits. As would be expected, the analysis also found a strong association with variants of another gene, APOE, that has long been known to be associated with the development of Alzheimer’s. The effect of BCHE was independent of APOE, however. Moreover, the effects of the two genes were additive -- that is, people with the suspect variants of both genes had more plaque deposits than people who had only one of the variants associated with plaque development.

Download a copy of the paper here.


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