For years, functional and precision medicine has centered on one foundational idea: heal the gut to improve health. But according to functional medicine pioneer Dr. Jeffrey Bland, the next evolution of medicine may begin somewhere even more fundamental.
The immune system.
In a recent TruNeura Mastermind session, members reviewed Dr. Bland’s keynote from the Personalized Lifestyle Medicine Institute (PLMI) 2025 conference, followed by a discussion with James Maskell and Kristine Burke about what these emerging discoveries mean for clinicians working to reverse cognitive decline.
The takeaway was clear. Understanding immune function is becoming essential for delivering precision brain health care.
A Nobel Prize That Could Reshape Clinical Practice
Dr. Bland opened his presentation by explaining why the recent Nobel Prize in Physiology or Medicine represents a major milestone for clinicians.
The award recognized discoveries surrounding regulatory T cells (Tregs) and the FOXP3 transcription factor, which helps regulate immune balance by influencing the expression of more than 1,000 genes.
Even more compelling, emerging research suggests that FOXP3 activity may be influenced by nutrition and lifestyle factors, including:
Vitamin D
Omega-3 fatty acids
Vitamin C
Vitamin A
Dietary polyphenols
For clinicians practicing precision medicine, this reinforces an important concept. Lifestyle interventions are not simply supportive care. They may directly influence the biological systems responsible for regulating inflammation and immune resilience.
Why This Matters for Cognitive Decline
Alzheimer’s disease and other neurodegenerative conditions are increasingly understood through the lens of chronic inflammation, immune dysregulation, and metabolic dysfunction.
As James Maskell pointed out during the discussion, many of today’s leading experts in cognitive decline, including Dr. Dale Bredesen, Dr. David Perlmutter, and Dr. Robert Lustig, are converging around the role of immunometabolism.
Rather than viewing cognitive decline solely as a neurological condition, clinicians are beginning to recognize it as a systems biology problem involving:
Immune regulation
Metabolic health
Environmental exposures
Mitochondrial function
Lifestyle factors
This systems approach aligns closely with TruNeura’s precision medicine framework.
Looking Beyond Traditional Inflammatory Markers
One of the most practical sections of Dr. Bland’s presentation focused on inexpensive, accessible tools that may provide deeper insight into immune function.
Among them were two indices calculated directly from a standard CBC with differential:
Systemic Immune-Inflammation Index (SII)
SII combines platelet, neutrophil, and lymphocyte counts into a single value that reflects systemic inflammatory tone.
Research suggests SII may correlate with:
Cardiometabolic disease
Autoimmune conditions
Chronic inflammation
Overall health status
Because it requires no additional laboratory testing, it can be incorporated into routine patient evaluations.
Systemic Inflammation Response Index (SIRI)
SIRI uses neutrophils, monocytes, and lymphocytes to evaluate a different aspect of immune activation.
Together, SII and SIRI provide clinicians with complementary perspectives on immune balance using laboratory data they may already collect.
Introducing suPAR
Perhaps the newest biomarker discussed during the Mastermind was soluble urokinase plasminogen activator receptor, commonly known as suPAR.
Unlike highly reactive markers such as hs-CRP, suPAR appears to remain relatively stable over time and may better reflect chronic immune activation rather than short-term inflammatory changes.
According to Dr. Bland, suPAR has shown associations with:
Cardiovascular disease
Chronic kidney disease
Diabetes
Frailty
Mortality risk
James Maskell noted that one of suPAR’s most interesting characteristics is that meaningful improvements appear to require sustained lifestyle changes over time, making it a potentially valuable tool for monitoring long-term patient engagement and biological progress.
Although suPAR remains an emerging biomarker in functional medicine, many clinicians are watching its development with great interest.
Building a Better Patient Journey
The Mastermind discussion also explored how these biomarkers may eventually reshape patient onboarding and care pathways.
Rather than jumping immediately into comprehensive cognitive decline programs, practices may eventually create staged evaluations that help patients better understand what’s driving their symptoms before committing to more extensive care.
This type of structured journey can improve patient education while reinforcing the value of precision diagnostics.
As James Maskell emphasized, the future of cognitive decline care will depend not only on advanced interventions but also on helping patients understand why those interventions are needed.
Precision Medicine Requires Precision Measurement
One of Dr. Bland’s strongest messages was that clinicians need objective ways to measure immune function over time.
He highlighted a broader framework that includes metrics such as:
Waist-to-hip ratio
Grip strength
Heart rate variability (HRV)
Sleep metrics
Body temperature
Daily movement
Cognitive assessments
Immune biomarkers
Together, these measurements create a more complete picture of biological resilience than any single laboratory value alone.
The Future of Brain Health Is Systems Biology
The field of cognitive decline is moving beyond isolated diagnoses toward understanding the interconnected biology driving disease progression.
Immune function, metabolism, environmental factors, mitochondrial health, and lifestyle are increasingly recognized as part of the same conversation.
For clinicians committed to reversing cognitive decline, staying current with these emerging models will become increasingly important.
TruNeura Mastermind sessions are designed to bring these evolving concepts into practical clinical discussion, helping providers translate cutting-edge research into better patient care.
Interested in Offering suPAR Testing?
As interest in immunometabolism and precision biomarkers continues to grow, suPAR is emerging as a valuable tool for assessing chronic immune activation and tracking long-term lifestyle interventions. If you’re a clinician interested in incorporating suPAR into your practice, you can now apply to become one of the first partners in the US.
👉 Learn more about becoming a suPAR provider
Ready to Build Your Cognitive Decline Program?
If you’re ready to strengthen your cognitive decline program with structured implementation support, precision medicine tools, and a collaborative clinical community, book a TruNeura Success Planning Session to explore how we can help you build and grow your practice.
