FROM OBSERVATION TO INVESTIGATION
The gap between understanding and treatment
Throughout clinical practice, a recurring pattern emerges: patients with cognitive symptoms that do not fit neatly into classic Alzheimer's disease, but instead show signs of vascular or microvascular dysfunction. Their MRIs reveal white matter hyperintensities rather than focal hippocampal atrophy. Their symptoms fluctuate — worsening with stress, poor sleep, illness, or uncontrolled blood pressure.
For years, this left a sense of therapeutic frustration. We could describe the problem — impaired blood flow at the microvascular level — but had few tools to actively target it. That gap between understanding and treatment is what ultimately led to our current research program.
This research evaluates whether a medication that improves microvascular function — tadalafil — can measurably enhance cerebral blood flow (CBF) and cognitive performance in patients with suspected vascular brain disease.
THE CORE QUESTION
Why focus on microvascular function?
The brain's smallest blood vessels regulate moment-to-moment delivery of oxygen and glucose to neurons. When these vessels lose their ability to dilate and constrict appropriately — a process known as impaired vascular reactivity — cognition suffers.
Most current dementia treatments focus on protein accumulation, not blood flow. Our research asks a different question:
“What if improving microvascular function could improve brain performance — even in the absence of amyloid-targeting therapy?”
MICROVASCULAR DYSFUNCTION IS LINKED TO
THE INTERVENTION
Why Tadalafil?
Tadalafil is a PDE5 inhibitor — a class of medications originally developed to treat vascular disease — that targets the same NO-mediated vasodilation mechanism central to healthy microvascular function.
Improves endothelial responsiveness
Targets the vascular endothelium directly, restoring the capacity for dynamic blood flow regulation.
Long half-life
Allows steady, sustained vascular effects rather than short-term spikes in perfusion.
FDA-approved safety profile
Well-characterized from decades of clinical use, reducing unknowns in a neurologic population.
Neurovascular alignment
Does not target amyloid or tau — instead targets the vascular system that sustains neuronal function, directly aligned with the BrainFlow framework.
Important: Tadalafil is not currently approved for the treatment of cognitive impairment or dementia. No conclusions should be drawn until rigorous data analysis is complete. This research is ongoing.
STUDY DESIGN
Who we enroll & how the trial works
Our research program enrolls adults whose profile reflects the patients most commonly seen in real-world neurology clinics — individuals whose symptoms are significant, but whose diagnoses are often ambiguous.
OUTCOMES WE MEASURE
CBF velocity & reactivity
Changes in cerebral blood flow measured non-invasively
Cognitive performance
Standardized testing at baseline and follow-up
Cognitive variability
Stability or improvement in day-to-day fluctuations
Safety & tolerability
Careful monitoring in a neurologic population
WHY THIS MATTERS
Intervening at the level of vascular function — before late-stage pathology sets in
If our hypothesis proves correct, it would represent a meaningful shift in how we approach cognitive aging and dementia risk. Rather than focusing exclusively on late-stage pathology, we may be able to intervene earlier — at the level of vascular function — when the brain still has reserve and adaptability.
This work reflects a broader evolution in brain health science: a growing recognition that blood flow is not secondary to cognition, but foundational to it. As we continue to explore exercise, vascular control, supplements, and medications that support the microvasculature, the goal is not to find a single miracle therapy, but to build layered, rational strategies that help patients maintain clarity, independence, and quality of life.
Better daily functioning
Reduced cognitive fluctuations
Slower progression of vascular cognitive impairment
RESEARCH PARTICIPATION
Considering participation in microvascular brain research?
Clinical research plays a critical role in advancing our understanding of brain health. Participation is always voluntary and should be undertaken thoughtfully. You may be a potential candidate if you have cognitive symptoms such as memory lapses or slowed thinking, white matter changes or small-vessel disease on MRI, and are interested in a proactive, science-based approach to brain health.
What participation involves
Important to understand
Explore the tools built from this research
Our vascular research directly informs the BrainFlow book, the Neurovasa supplement, and the Brain Age screening tool.