Jan. 29, 2019 – What if solving brain games and puzzles on a computer could reduce the chances of developing dementia such as Alzheimer’s or delay the debilitating loss of function associated with the disease?

That’s the question researchers from the University of South Florida (USF) are seeking to answer through a pioneering new study that will test a training regimen designed to improve brain function. Using a $2.7-million grant from the National Institutes of Health (NIH), the researchers are developing a clinical trial for up to 1,600 older adults, who will learn a mental exercise routine focused on processing information to target cognitive improvements over time.

“This is a large primary prevention trial to examine if computerized cognitive exercises will reduce the risk of dementia,” said Elizabeth Hudak, PhD, research assistant professor at the USF Health Morsani College of Medicine (MCOM). “It is the first-of-its-kind study that will train adults on these exercises.”

As one ages, cognitive functions associated with thinking and memory can decline. Dementia is a general term for a decline that interferes with daily life, and Alzheimer’s is the most common form of dementia.

An estimated 5.7 million Americans live with Alzheimer’s today. By 2050, the number is projected to rise to nearly 14 million, according to the Alzheimer’s Association.

The primary investigators of the new study “Preventing Alzheimer’s Disease with Cognitive Training” are Jerri Edwards, PhD, of the MCOM Department of Psychiatry and Behavioral Neurosciences and David Morgan, PhD, of Michigan State University. They will oversee four training facilities, three in Tampa Bay and one in Michigan, which will each host up to 400 older adults.

One of the training sites will be located on the campus of USF St. Petersburg (USFSP).

“What we have learned is that the types of activities people do as they age really matter,” said Jennifer O’Brien, PhD, assistant professor of psychology who will supervise data collection and analysis at USFSP. “Those that target these cognitive functions that continue to challenge a person and adapt with performance across time are beneficial to improving quality of life.”

The clinical trial at USF will consist of a variety of brain games on a computer in which participants are asked to indicate what they saw or heard and solve puzzles. Each participant will visit a training facility three times to learn how to follow the mental regimen. Over three years, they will complete a total of 45 hours of computerized training exercises on their own. Researchers will then monitor for cognitive improvements or signs of decline.

Prior studies have shown such training is an effective way to reduce chances of developing dementia. In 2017, findings from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study showed that among nearly 3,000 healthy older adults, those who completed 11 or more computerized sessions were up to 48 percent less likely to develop dementia across a 10-year period than adults who did no exercises at all.

“Cognitive training enhances mental quickness and visual attention, improves gait speed and balance, promotes safer and prolonged driving mobility and maintains health and well-being, including protection against depression,” said Alisa Houseknecht, coordinator of the clinical trial at USF.

The researchers will recruit adults age 65 and older who are willing to commit to the exercise training and are not experiencing dementia or other forms of neurological disease. A family history of Alzheimer’s does not disqualify a person.

Ultimately, researchers hope this short-term study will show enough feasibility for a longer, more rigorous clinical trial in the future. If the researchers can enroll 1,600 older adults in the trial, the research team will apply for a larger grant to train and monitor a cohort of participants for five to seven years. For the follow-up study, neuroimaging of the brain and genetic testing will be incorporated to get a better understanding of which individuals are more likely to develop dementia and would benefit from this training.

“We will be looking across time to see who ends up with dementia and who does not,” O’Brien said. “We estimate that even if this intervention delays onset of dementia by only one year, that would be 9.2 million fewer cases across the next 30 years.”

For more information about the clinical trial, visit: www.pactstudy.org or call the Cognitive Aging Lab at 813-974-6703.

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.

 – USF Health –

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