UC Berkeley awarded $47 million grant to study how healthy lifestyle changes the aging brain

The University of California, Berkeley announced today that it has received a five-year grant expected to total $47 million from the U.S. National Institute on Aging (NIA) to incorporate advanced brain imaging into the Alzheimer's Association's groundbreaking clinical trial, the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to determine whether lifestyle changes can protect memory in people at risk of developing dementia.

The expanded study will be the first large-scale investigation of how lifestyle interventions, including exercise, diet, cognitive stimulation and health coaching, affect well-known biological markers of Alzheimer's and dementia in the brain.

U.S. POINTER is a $35 million Alzheimer's Association-led two-year clinical study to test whether lifestyle interventions focused on combining healthy nutrition, physical activity, social and intellectual challenge, and increased medical monitoring of vascular and metabolic conditions can protect cognitive function in older adults (60-79 years old) who are at increased risk for cognitive decline later in life. U.S. POINTER is the first study to examine these combined multidimensional interventions in a large-scale U.S.-based population.

The new award of $47 million from the NIA, part of the U.S. National Institutes of Health, (NIH grant number R01AG062689) will support the U.S. POINTER Neuroimaging Ancillary Study, which will use advanced brain imaging techniques (amyloid positron emission tomography (PET), tau PET and magnetic resonance image (MRI) scans) to assess the biological effects of these lifestyle interventions on brain health, including overall and regional brain shape, size and blood flow, and on indicators of heart health risk and small vessel disease.

Susan Landau, Ph.D., a research neuroscientist at UC Berkeley's Helen Wills Neuroscience Institute, is principal investigator of the add-on study.

"A healthy diet and lifestyle are generally recognized as good for health, but U.S. POINTER is the first large randomized controlled trial to look at whether lifestyle changes actually influence Alzheimer's disease-related brain changes," said Landau. "Lifestyle modification is a non-drug option that is accessible to people and may reduce the likelihood of developing Alzheimer's."

"The U.S. POINTER trial gives us an opportunity to ask whether diet and exercise can actually change the brain, and ultimately the risk of Alzheimer's and other dementias," Landau added.

The proposed study responds to the 2018 NIA Research Summit recommendations that encourage rigorous investigations of lifestyle change as a disease-modifying therapy to prevent Alzheimer's and other dementias.

This groundbreaking project is an unparalleled examination of how lifestyle 'therapies' may change our brain in ways that are related to Alzheimer's disease, vascular dementia and overall brain health.

U.S. POINTER is designed to determine what lifestyle interventions have a tangible impact on our brains. The addition of brain imaging is an important component that could provide the roadmap for brain health to reduce the risk of dementia before symptoms have a chance to appear."

Maria C. Carrillo, Ph.D., Chief Science Officer of the Alzheimer's Association

Public health implications

According to the Alzheimer's Association 2019 Alzheimer's Disease Facts and Figures report, an estimated 5.8 million Americans of all ages are living with Alzheimer's dementia, and Alzheimer's is the sixth-leading cause of death in the U.S. Barring the development of medical breakthroughs, the number may nearly triple to 13.8 million by 2050.

Previous results suggest that the benefits of lifestyle changes on brain health in older adults are potentially larger than pharmacological treatments tested to date. In addition, healthful lifestyle modification is an affordable and accessible approach with health benefits that extend beyond brain health.

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed that in at-risk adults, lifestyle intervention improved cognitive function by 25 percent relative to adults randomized to health education. The success of FINGER led to the initiation of U.S. POINTER and multiple additional national studies based on that model, now being coordinated through an interdisciplinary global network known as World Wide FINGERS.

A critical feature of the U.S. POINTER trial is its recruitment approach, which aims to include a geographically and racially/ethnically diverse population. This can help ensure the intervention will be applicable to a large proportion of older individuals. Four sites (Winston-Salem, NC; Houston, TX; Davis, CA, and Chicago, IL) have been chosen for U.S. POINTER, with one more site planning to come online later this year.

Just over one-half of the U.S. POINTER Study participants (up to 1,250 out of 2,000) will be assessed with PET imaging at study start and at two years to measure the buildup of amyloid and tau, two proteins whose accumulation in the brain has been linked to Alzheimer's dementia, and MRI at baseline, one year, and two years to measure the size of brain regions, identify lesions related to strokes or other vascular changes, and observe changes in brain blood flow.

Landau notes:

Brain markers of dementia, when measured at the beginning of the study, may predict who will respond best to the interventions, which could inform future precision medicine approaches to healthcare."

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