For testing a drug in patients with early signs of cognitive impairment but no functional disability, just improvement in memory and thinking ability would be an acceptable trial goal.
The deletion of just a single enzyme saw the near total reversal of the deposition of amyloid plaques found in brains of those with Alzheimer's, improving cognitive functions in the mouse subjects, according to the study from researchers at the Cleveland Clinic, published February 14 in the Journal of Experimental Medicine. Brain Institute at UT Southwestern.
Loss of BACE1 also improved the learning and memory of mice with Alzheimer's disease. The researchers determined that lower fitness levels were associated with weaker white matter, which in turn correlated with lower brain function.
Interestingly, unlike previous studies that relied on study participants to assess their own fitness, this study objectively measured cardiorespiratory fitness with a scientific formula called maximal oxygen uptake. Cut out BACE1 completely and the brain's functionality will be seriously damaged.
The study adds to a growing body of evidence pointing to a simple yet crucial mandate for human health: Exercise regularly. "We are grateful to the patients and caregivers who participated in this study, and despite this outcome, Merck remains committed to developing novel therapies for the treatment of Alzheimer's and other neurodegenerative diseases". For instance, what fitness level is needed to notably reduce the risk of dementia? Is it too late to intervene when patients begin showing symptoms? This comes after years of research and clinical trials up to this point.
"Evidence suggests that what is bad for your heart is bad for your brain", noted senior study author Rong Zhang, Ph.D., a professor at UT Southwestern and director of the cerebrovascular laboratory in the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas.
Researchers at the Cleveland Clinic Lerner Research Institute have found that gradually depleting a specific enzyme in the brain could be the key to undoing the damage caused by the debilitating brain disease.
An ongoing five-year national clinical trial conducted at the same institute is now seeking to determine if combinations of aerobic exercise and certain medications can help preserve brain function. It involves more than 600 older adults at high risk to develop Alzheimer's disease.
At left, the brain of a mouse with Alzheimer's disease full of amyloid plaques shown in red, surrounded by activated microglial cells, in green.
Merck & Co has ended a second phase 3 trial of its Alzheimer's drug, verubecestat, after an interim analysis found that it was unlikely to succeed in slowing the progression of the disease in its early stages. "But, eventually, the hope is that our studies will convince people to exercise more".