Chapter 111
Neurodegeneration — 17
GLP-1 drugs work predominantly through the brain and reduce brain inflammation. There are ongoing clinical trials testing these drugs to prevent progression in early Alzheimer’s disease and Parkinson’s disease, well beyond their current role in treating diabetes and obesity. It would not be at all surprising if such agents that safely and durably block brain inflammation, when given early enough in people at high risk of neurodegenerative diseases, would ultimately render some protection. Our ability for identifying who and when is rapidly improving with the growing acceptance of biomarkers and use of multimodal AI to process all the layers of a person’s data.
There are other novel approaches to promoting brain health in people. In five participants with mild Alzheimer’s disease, the first senolytic clinical trial targeted brain cellular senescence using the combination of dasatinib, a tyrosine kinase inhibitor used in treating cancer, and quercetin, a natural flavonoid. This combination has been studied in experimental models and shown to be synergistic (beyond additive, as in 1 + 1 = 3) for the goal of inducing the death of senescent cells. After twelve weeks of therapy, blood and cerebrospinal biomarkers suggested a reduction in senescent cells. This first small foray trial without controls can be viewed as a very early step for possible senolytic therapy for preserving brain health.
Beyond these pharmacologic approaches, noninvasive device neuromodulation, with transient alternating current stimulation, has been shown to improve memory in people aged sixty-five to eighty-eight years. In a small randomized trial with sham controls, four days of treatment led to sustained benefit in memory one month later.
As these approaches go forward in clinical trials with controls, we will be able to determine brain-specific changes of aging using plasma proteins and MRI imaging. That’ll facilitate a determination of whether they are working, promoting brain health, slowing the progression of aging, or even achieving a rejuvenating impact.
Before moving on, just a quick note about nootropic supplements that are purported to improve learning and memory, such as Alpha Brain, Neuriva, Kin Euphorics, several amino acids, herbal extracts, probiotics, and other substances. None of these have any meaningful clinical trial data to support their use.
Countering the neurodegeneration that occurs with aging, no less with Alzheimer’s and Parkinson’s, remains one of the most formidable challenges for promoting health span. I think of it as one of the big killers in the second half of our lives because extending lifespan without preserving cognitive function is not appealing to anyone. Fortunately, from the culmination of a large body of recent studies, we may be on the cusp of breaking through with new ways to promote brain health so that when we reach advanced age, we’re cognitively crisp.
The implications of the current historic convergence of breakthroughs in medical science are broader than is easy to grasp for even the sharpest mind.