TAMPA, Fla. (April 6, 2021) — The National Institutes of Health (NIH) has awarded the University of South Florida (USF) total expected funds of $44.4 million over the next five years to study whether computerized brain training exercises can reduce the risk of mild cognitive impairment (MCI), and dementias like Alzheimer’s disease, in older adults.

The grant from the NIH’s National Institute on Aging, supported under Award Number R01AG070349, expands USF’s Preventing Alzheimer’s with Cognitive Training (PACT) study. PACT will be the largest primary prevention trial to date designed to rigorously test the effectiveness of computer-based training to protect against MCI and dementias. Dementia such as Alzheimer’s disease leads to a loss in thinking, reasoning, memory, and everyday functional abilities.

“We are grateful for the willingness of the Tampa Bay community to support our efforts to prevent Alzheimer’s disease and dementia by participating in the PACT trial,” said USF site principal investigator Jerri Edwards, PhD, a professor of psychiatry and behavioral neurosciences at the USF Health Morsani College of Medicine. “Because of their willingness to join us in the fight against Alzheimer’s disease, we can now expand this trial across the U.S. with hope of ultimately reducing dementia incidence.”

No proven treatments yet exist to cure or stop the progression of Alzheimer’s disease, the most common form of dementia. Dementia prevention research like that done by Dr. Edwards and her team takes on increased urgency, because the few Alzheimer’s medications currently on the market primarily provide short-term management of symptoms for those who already have dementia. Alzheimer’s disease afflicts 5.8 million Americans, including one in every 10 people age 65 and older, according to the Alzheimer’s Association. Without effective interventions, the human and economic costs for those living with dementia, their caregivers, and the health care system will continue to rise as the population ages.

“If we can reduce the chances of progressing to Alzheimer’s disease and related dementias with a cognitive training regimen – an inexpensive and safe non-drug intervention – that would be a huge public health advance,” Dr. Edwards said. “Research suggests that delaying the onset of dementia by even one year would result in millions of fewer cases over the next 30 years.”

Jerri Edwards, PhD, professor of psychiatry and behavioral neurosciences at the USF Health Morsani College of Medicine, is  USF site principal investigator for the PACT study.

The multisite trial is expected to expand the study to enroll 7,600 healthy adults at various US locations who are ages 65 and older with no signs of cognitive impairment or dementia. People with mild cognitive impairment experience more memory problems than expected for those the same age. MCI can increase the risk for dementia. Within two years, Dr. Edwards said, about 15% of people with MCI progress to dementia with more serious cognitive decline that interferes with everyday tasks, such as preparing a meal, doing laundry, or driving.

Published research by Dr. Edwards and others indicates that targeted computerized training can help maintain mental and physical function. In the breakthrough Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, healthy older adults randomized to receive such training had a 29% lower risk of dementia after 10 years than the untreated control group. Those completing additional training benefited even more; they were 48% less likely to show signs of dementia 10 years later.

“As an academic medical center with a growing Neuroscience Institute and well-established Byrd Alzheimer’s Center, USF Health is at the forefront of the latest research attacking Alzheimer’s disease and related dementias on multiple fronts,” said Charles J. Lockwood, MD, senior vice president of USF Health and dean of the USF Health Morsani College of Medicine. “This pivotal study, based on compelling preliminary evidence, moves us one step closer to answering a critical question: Can computer-based cognitive training prevent dementia and help keep our brains healthy as we age?”

With the PACT study, Dr. Edwards’ team seeks more conclusive evidence about whether and how computerized training can protect against age-related cognitive impairment and dementia. The researchers will identify through comprehensive medical evaluation any study participants who develop MCI or dementia three years after enrollment in the PACT study. They will use brain scans to diagnose dementia such as Alzheimer’s disease and to see if those with amyloid protein in the brain (a hallmark protein of the neurodegenerative disease) benefit from the training.

Dr. Edwards emphasizes the need for more African-American and Hispanic/Latino study volunteers as the Alzheimer’s Association reports they are populations at highest risk for Alzheimer’s disease and other dementias.

USF Health expects to continue enrolling participants across the Tampa Bay region in the PACT study over the next three years. Study participants cannot have dementia or other neurological disorders, but a family history of Alzheimer’s disease does not disqualify an otherwise healthy person. Two initial supervised training sessions will be conducted onsite (with strict adherence to CDC guidelines for COVID-19), and study participants will complete the remaining brain training sessions independently at home over the next two years.

For more information, please visit the PACT study website at pactstudy.org or call (813) 974-6703.

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Researchers from the University of South Florida and the University of Miami say the case control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset.  Their findings appear in the online version of an article  published June 5 in the Journal of Alzheimer’s Disease. The collaborative study involved 124 people, ages 65 to 88, in Tampa and Miami.

“These intriguing results suggest that older adults with mild memory impairment who drink moderate levels of coffee — about 3 cups a day — will not convert to Alzheimer’s disease — or at least will experience a substantial delay before converting to Alzheimer’s,” said study lead author Dr. Chuanhai Cao, a neuroscientist at the USF College of Pharmacy and the USF Health Byrd Alzheimer’s Institute. “The results from this study, along with our earlier studies in Alzheimer’s mice, are very consistent in indicating that moderate daily caffeine/coffee intake throughout adulthood should appreciably protect against Alzheimer’s disease later in life.”

The study shows this protection probably occurs even in older people with early signs of the disease, called mild cognitive impairment, or MCI.  Patients with MCI already experience some short-term memory loss and initial Alzheimer’s pathology in their brains.  Each year, about 15 percent of MCI patients progress to full-blown Alzheimer’s disease.  The researchers focused on study participants with MCI, because many were destined to develop Alzheimer’s within a few years.

Blood caffeine levels at the study’s onset were substantially lower (51 percent less) in participants diagnosed with MCI who progressed to dementia during the two-to-four year follow-up than in those whose mild cognitive impairment remained stable over the same period.

No one with MCI who later developed Alzheimer’s had initial blood caffeine levels above a critical level of 1200 ng/ml – equivalent to drinking several cups of coffee a few hours before the blood sample was drawn.  In contrast, many with stable MCI had blood caffeine levels higher than this critical level.

“We found that 100 percent of the MCI patients with plasma caffeine levels above the critical level experienced no conversion to Alzheimer’s disease during the two-to-four year follow-up period,” said study co-author Dr. Gary Arendash.

The researchers believe higher blood caffeine levels indicate habitually higher caffeine intake, most probably through coffee.  Caffeinated coffee appeared to be the main, if not exclusive, source of caffeine in the memory-protected MCI patients, because they had the same profile of blood immune markers as Alzheimer’s mice given caffeinated coffee. Alzheimer’s mice given caffeine alone or decaffeinated coffee had a very different immune marker profile.

Since 2006, USF’s Dr. Cao and Dr. Arendash have published several studies investigating the effects of caffeine/coffee administered to Alzheimer’s mice.   Most recently, they reported that caffeine interacts with a yet unidentified component of coffee to boost blood levels of a critical growth factor that seems to fight off the Alzheimer’s disease process.

USF Health's Dr. Chuanhai Cao, study lead author

“We are not saying that moderate coffee consumption will completely protect people from Alzheimer’s disease,” Dr. Cao cautioned.  “However, we firmly believe that moderate coffee consumption can appreciably reduce your risk of Alzheimer’s or delay its onset.”

Alzheimer’s pathology is a process in which plaques and tangles accumulate in the brain, killing nerve cells, destroying neural connections, and ultimately leading to progressive and irreversible memory loss.  Since the neurodegenerative disease starts one or two decades before cognitive decline becomes apparent, the study authors point out, any intervention to cut the risk of Alzheimer’s should ideally begin that far in advance of symptoms.

“Moderate daily consumption of caffeinated coffee appears to be the best dietary option for long-term protection against Alzheimer’s memory loss,” Dr. Arendash said.  “Coffee is inexpensive, readily available, easily gets into the brain, and has few side-effects for most of us. Moreover, our studies show that caffeine and coffee appear to directly attack the Alzheimer’s disease process.”

In addition to Alzheimer’s disease, moderate caffeine/coffee intake appears to reduce the risk of several other diseases of aging, including Parkinson’s disease, stroke, Type II diabetes, and breast cancer.  However, supporting studies for these benefits have all been observational (uncontrolled), and controlled clinical trials are needed to definitively demonstrate therapeutic value.

A study tracking the health and coffee consumption of more than 400,000 older adults for 13 years, and published earlier this year in the New England Journal of Medicine, found that coffee drinkers reduced their risk of dying from heart disease, lung disease, pneumonia, stroke, diabetes, infections, and even injuries and accidents.

With new Alzheimer’s diagnostic guidelines encompassing the full continuum of the disease, approximately 10 million Americans now fall within one of three developmental stages of Alzheimer’s disease — Alzheimer’s disease brain pathology only, MCI, or diagnosed Alzheimer’s disease.  That number is expected to climb even higher as the baby-boomer generation continues to enter older age, unless an effective and proven preventive measure is identified.

“If we could conduct a large cohort study to look into the mechanisms of how and why coffee and caffeine can delay or prevent Alzheimer’s disease, it might result in billions of dollars in savings each year in addition to improved quality of life,” Dr. Cao said.

The USF-UM study was funded by the NIH-designated Florida Alzheimer’s Disease Research Center and the State of Florida.

Article citation:
“High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia;”  Chuanhai Cao, David A. Lowenstein, Xiaoyang Lin, Chi Zang, Li Wang, Ranjan Duara, Yougui Wu, Alessandra Giannini, Ge Bai, Jianfeng Cai, Maria Greig, Elizabeth Schofield, Raj Ashok, Brent Small, Huntington Potter and Gary W. Arendash;  Journal of Alzheimer’s Disease, 29 (2012) 1-14,  DOI 10.3233/JAD-2012-111781.

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USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities.

Media contacts:
Shani Jefferson, USF Health Byrd Alzheimer’s Institute, 813-396-0675 or  sjeffer1@health.usf.edu
Anne DeLotto Baier, USF Health Communications, (813) 974-3303 or abaier@health.usf.edu