Inflammation as a Unifying Signal: Biomarkers, Glucose Variability, and the Heart–Brain Axis

Fred Shaffer
3 hours ago
27 min read

Executive Summary

Inflammation has become the common language linking coronary disease, metabolic dysfunction, autonomic dysregulation, and part of the biology of neurodegeneration.

In atherosclerosis, the evidence is now causal and clinically actionable because lipids accumulate, innate immune pathways activate, high-sensitivity C-reactive protein can expose residual inflammatory risk, and selected anti-inflammatory therapies can reduce events (Mensah et al., 2025; Ridker et al., 2002; Ross, 1999).

In Alzheimer’s disease, the picture is biologically compelling but therapeutically unfinished because neuroinflammation, microglial activation, and blood-brain barrier dysfunction are clearly involved, yet broad anti-inflammatory drug trials have not reliably slowed disease (Aisen et al., 2003; De Strooper & Karran, 2016; Heneka et al., 2013; Meyer et al., 2019; Sims et al., 2017).

For the practicing clinician, three complementary biomarkers triangulate this systemic inflammatory burden. High-sensitivity C-reactive protein indexes peripheral immune activation, heart rate variability (HRV) metrics such as the natural log of very low frequency power (LnVLF) capture vagal anti-inflammatory tone, and a specific electroencephalographic pattern called spindling excessive beta can signal cortical involvement in refractory psychiatric presentations (Morrow et al., 2025; Shaffer & Ginsberg, 2017; Sproston & Ashworth, 2018). Together these measures help separate immune-driven clinical pictures from symptom-defined diagnoses.

Glucose variability sharpens this story because repeated swings, especially postprandial excursions, meaning after-meal spikes, appear capable of provoking oxidative stress, endothelial dysfunction, and inflammatory signaling in the cardiovascular system. These swings may also amplify neurovascular stress in the brain, even when fasting glucose or hemoglobin A1c looks acceptable.

Continuous glucose monitoring (CGM) can reveal these patterns directly, although targets outside established diabetes are not yet standardized (Battelino et al., 2019; Ceriello et al., 2008; Spartano et al., 2025; Watt et al., 2020; Zahalka et al., 2024).

In coronary disease, inflammation already belongs in risk assessment and sometimes in treatment.

In dementia prevention and refractory psychiatric care, the most actionable anti-inflammatory strategy remains meticulous vascular and metabolic care, along with targeted biomarker assessment, rather than broad-spectrum pharmacotherapy (Ngandu et al., 2015; Swatzyna et al., 2024; Williamson et al., 2019).

Inflammation as a Common Language

The connection between the immune system and the nervous system is a bidirectional physiological pathway. When the body experiences chronic low-grade inflammation, the effects extend far beyond localized tissues because inflammatory cytokines, meaning immune signaling proteins, instruct the brain and autonomic nervous system to shift their operational states (Dantzer, 2018). The result is widespread systemic distress that crosses traditional diagnostic boundaries.

Identifying this disruption requires clinicians to evaluate multiple biological markers simultaneously rather than relying on a single number. C-reactive protein, heart rate variability, and specific electroencephalographic patterns each open a different diagnostic window into the same physiology (Morrow et al., 2025; Shaffer & Ginsberg, 2017; Sproston & Ashworth, 2018). Glucose instability underlies all three and warrants parallel attention (Watt et al., 2020).

From Clogged Pipes to Immune Battlefields

The artery is no longer best imagined as a passive pipe collecting debris. It is more accurately described as a chronically injured tissue staging an immune response, and images of sharp cholesterol crystals inside plaque reflect real pathology rather than metaphor (Duewell et al., 2010).

Atherosclerosis, the chronic buildup of lipid-rich plaque in the arterial wall, begins when cholesterol-bearing particles are retained beneath the endothelium, the thin cell layer that lines blood vessels. Prospective studies then showed that hs-CRP, a sensitive blood marker of low-grade systemic inflammation, predicts first cardiovascular events and adds information beyond low-density lipoprotein (LDL) cholesterol alone (Ridker et al., 2002; Ross, 1999).

Cholesterol becomes more dangerous when it crystallizes. Cholesterol crystals activate the NLRP3 inflammasome, an intracellular danger-sensing complex, which promotes maturation of interleukin-1 beta, or IL-1β, a cytokine that amplifies downstream inflammatory signaling (Duewell et al., 2010).

This explains why statins are powerful but incomplete. In the JUPITER trial, rosuvastatin reduced events in people with relatively low LDL but elevated hs-CRP, reinforcing that lipid lowering and inflammation control are interlocking rather than rival explanations. Later guidance emphasized that some statin-treated patients still carry substantial residual inflammatory risk (Mensah et al., 2025; Ridker et al., 2008).

The most convincing proof of causality came from intervention. CANTOS showed that blocking IL-1β with canakinumab lowered recurrent vascular events without lowering LDL, whereas low-dose methotrexate lowered neither inflammatory biomarkers nor events (Ridker et al., 2017; Ridker et al., 2019). Pathway specificity matters, and “anti-inflammatory” is not a single pharmacologic category.

Colchicine sits closer to ordinary practice. Event reduction has been shown in recent studies of myocardial infarction and chronic coronary disease, but guidance remains selective rather than universal, as benefit appears clearest in well-chosen secondary-prevention populations (Nidorf et al., 2020; Tardif et al., 2019; Virani et al., 2023).

C-Reactive Protein: Reading the Systemic Signal

C-reactive protein (CRP) is an acute-phase protein synthesized rapidly by the liver, with production primarily triggered by interleukin-6, a pro-inflammatory cytokine released by macrophages during tissue damage or infection (Sproston & Ashworth, 2018). The high-sensitivity C-reactive protein (hs-CRP) assay is the clinical standard for measuring chronic low-grade inflammation. Serum levels at or above 3 mg/L are consistently associated with a higher risk of cardiovascular events, metabolic syndrome, and refractory depression.

CRP is more than a passive indicator of an immune response. It actively participates in the inflammatory cascade by binding to damaged cells and activating the complement system, a group of plasma proteins that amplify immune responses. Crucially for psychiatric and neurological health, elevated systemic inflammation can compromise the integrity of the blood-brain barrier (Dantzer, 2018).

Increased permeability allows peripheral inflammatory mediators to infiltrate the central nervous system. Once inside, these mediators trigger a cascade of neuroinflammation that profoundly alters brain function and neurotransmission (DiSabato, Quan, & Godbout, 2016). That mechanism is part of why hs-CRP elevation is relevant well beyond cardiology clinics.

In cardiovascular prevention, hs-CRP is most useful when risk decisions are uncertain or when residual risk remains despite apparently good LDL control. In primary prevention, hs-CRP at or above 2 mg/L functions as a risk-enhancing factor, and in secondary prevention it can help identify residual inflammatory risk that standard lipid measures understate (Arnett et al., 2019; Mensah et al., 2025; Virani et al., 2023).

However, CRP has not become an Alzheimer’s biomarker because peripheral inflammatory markers relate to dementia risk imperfectly and are not specific for Alzheimer’s disease (Darweesh et al., 2018).

C-Reactive Protein: Reading the Systemic Signal

C-reactive protein (CRP) is an acute-phase protein synthesized rapidly by the liver, with production primarily triggered by interleukin-6, a pro-inflammatory cytokine released by macrophages during tissue damage or infection (Sproston & Ashworth, 2018). The high-sensitivity assay, hs-CRP, is the clinical standard for measuring chronic low-grade inflammation. Serum levels at or above 3 mg/L are consistently associated with higher risk of cardiovascular events, metabolic syndrome, and refractory depression.

In cardiovascular prevention, hs-CRP is most useful when risk decisions are uncertain or when residual risk remains despite apparently good LDL control. In primary prevention, hs-CRP at or above 2 mg/L functions as a risk-enhancing factor, and in secondary prevention, it can help identify residual inflammatory risk that standard lipid measures understate (Arnett et al., 2019; Mensah et al., 2025; Virani et al., 2023).

Heart Rate Variability and the Vagal Anti-Inflammatory Pathway

Heart rate variability (HRV) measures beat-to-beat temporal fluctuations in heart rhythm. It serves as a direct, non-invasive window into the autonomic nervous system and its regulation by the vagus nerve. Respiratory sinus arrhythmia (RSA), the speeding and slowing of the heart across each breathing cycle, is an important parasympathetic HRV driver.

The vagus nerve is the primary conduit for parasympathetic signaling, which functions as the body’s physiological braking system against stress (Shaffer & Ginsberg, 2017).

Through the cholinergic anti-inflammatory pathway, vagal outflow directly dampens production of pro-inflammatory cytokines in the spleen and other organs (Pavlov & Tracey, 2012). When this system functions properly, peripheral inflammation is held in check. When it does not, cytokines continue to accumulate and signal upward to the brain.

Systemic inflammation disrupts this autonomic balance. High levels of circulating cytokines frequently produce vagal withdrawal, a state in which parasympathetic signaling is suppressed and the inflammatory response runs unchecked (Fagundes et al., 2011). In HRV analysis, this failure is reflected in the natural log of the very low frequency band, or LnVLF, which depends on parasympathetic outflow, thermoregulation, and the renin-angiotensin system (Shaffer & Ginsberg, 2017).

Depressed LnVLF power is therefore a robust physiological indicator of systemic distress. When a patient is inflamed, the complex, chaotic rhythms of a healthy heart collapse into rigid predictability, and the autonomic nervous system loses metabolic flexibility. For clinicians, persistently low LnVLF is a reasonable red flag for underlying chronic inflammatory processes that may warrant hs-CRP evaluation (Fagundes et al., 2011; Shaffer & Ginsberg, 2017).

Glucose Variability: The Hidden Driver of Low-Grade Inflammation

Glucose variability is the magnitude and frequency of glucose swings around a person’s mean. It includes after-meal spikes, overnight dips, and day-to-day instability, and it is commonly described with metrics such as standard deviation, mean amplitude of glycemic excursions (MAGE), and coefficient of variation (%CV). In diabetes care, a %CV below 36% is commonly treated as relatively stable (Battelino et al., 2019).

This matters because fasting glucose is a single snapshot and hemoglobin A1c (HbA1c) is an average. A patient can look acceptable on paper yet still have repeated postprandial surges, nocturnal lows, or wide day-to-day swings that never appear in a fasting specimen. HbA1c can also mislead when conditions affecting red-cell turnover distort the relationship between average glycemia and the laboratory measurement (Bergman et al., 2020).

Continuous glucose monitoring (CGM) measures interstitial glucose, meaning glucose in the fluid beneath the skin, every few minutes and displays mean glucose, time in range (TIR), time above range, time below range, and %CV. It can uncover clinically useful patterns even when fasting glucose or HbA1c seems reassuring (Battelino et al., 2019). Interpretation in people without diabetes is not yet fully standardized, and not every isolated spike warrants medicalization; however, a recent review concluded that the signal is strong enough to warrant clinical attention (Daya et al., 2025; Spartano et al., 2025; Zahalka et al., 2024).

How Glucose Swings Feed Vascular and Neural Inflammation

In the cardiovascular system, glucose swings behave less like background noise and more like repeated biochemical jolts. Experimental work showed that oscillating glucose can impair endothelial function and generate more oxidative stress than comparably elevated but steady glucose (Ceriello et al., 2008; Monnier et al., 2006).

Oxidative stress means excess reactive oxygen species that damage lipids, proteins, DNA, and vascular signaling, while endothelial dysfunction means the vessel lining becomes less able to dilate, resist clotting, and restrain inflammation.

That biology fits the inflammatory model of atherosclerosis. Reviews link greater glucose variability with inflammation, endothelial dysfunction, and a more prothrombotic state (Klimontov, 2021). Preclinical work after coronary stenting has associated variability with NLRP3 inflammasome signaling and reduced plaque stability (Xia et al., 2020).

Why the Retina, Kidneys, and Brain Notice the Swings

The retina and kidneys register these swings because both depend on exquisitely vulnerable microvascular beds. Greater variability measured by CGM has been associated with diabetic retinopathy, worsening endothelial and renal dysfunction, and faster progression to kidney failure in diabetes complicated by chronic kidney disease (Habte-Asres et al., 2022; Lu et al., 2019; Wei et al., 2016).

The brain is likely similarly exposed. Reviews and cohort studies link higher glucose variability to oxidative stress, neuroinflammation, and worse cognition, and a meta-analysis in type 2 diabetes found that greater acute variability was associated with higher odds of cognitive impairment (Chi et al., 2023; Watt et al., 2020). Notably, young-adult fasting-glucose variability below the diabetes threshold was associated with worse midlife cognition (Bancks et al., 2018). The causal chain is less secure than it is in coronary disease, but the signal is strong enough to matter clinically.

The Alzheimer Brain: Inflamed, Vascular, and Metabolically Exposed

The modern view of Alzheimer’s disease is no longer purely neuron-centric. Amyloid-β, a peptide that aggregates into plaques, and tau, a neuronal protein that can misfold into tangles, remain central, but the “cellular phase” of disease now includes astrocytes, microglia, and vascular cells (De Strooper & Karran, 2016). Human genetics has strengthened the case for microglial-mediated innate immunity in disease onset (Bellenguez et al., 2022; Sims et al., 2017).

The blood-brain barrier is part of the story. Endothelial low-density lipoprotein receptor-related protein 1 (LRP1) helps transport amyloid-β across that barrier, and recent single-nucleus transcriptomic studies in Alzheimer’s disease show disturbed endothelial and perivascular programs consistent with impaired angiogenesis and barrier dysfunction (Storck et al., 2016; Tsartsalis et al., 2024).

Peripheral inflammatory markers relate to later dementia risk in some studies, but meta-analytic work shows that they are not specific for Alzheimer’s disease. That helps explain why CRP has not become an Alzheimer biomarker in routine practice, even though inflammation clearly participates in disease biology (Darweesh et al., 2018).

Trial history reinforces the caution. Rofecoxib, naproxen, and celecoxib did not convincingly slow established Alzheimer’s disease or prevent it in early-prevention settings, suggesting that the wrong target, the wrong timing, or both may have been chosen (Aisen et al., 2003; Lyketsos et al., 2007; Meyer et al., 2019).

Glucose variability is therefore best viewed as a plausible metabolic amplifier of neurovascular and inflammatory stress, not as a proven stand-alone cause of Alzheimer’s disease (Watt et al., 2020).

Spindling Excessive Beta: A Cortical Signature of Neuroinflammation

When systemic inflammation crosses into the brain, it triggers activation of microglia, the resident immune cells of the central nervous system. While acute activation is protective, prolonged microglial activation releases cytokines that damage neurons and impair cognition (DiSabato et al., 2016). This chronic neuroinflammatory state mimics many psychiatric illnesses and contributes to fatigue, depression, and cognitive dysfunction (Rhie, Jung, & Shim, 2020). Detecting it traditionally required invasive or expensive procedures such as lumbar punctures or positron emission tomography.

Electroencephalography (EEG) has emerged as a non-invasive, cost-effective alternative for identifying cortical features consistent with inflammation. Clinicians should look for a distinct phenotype called spindling excessive beta, characterized by sinusoidal, spindle-like beta wave activity between 13 and 35 Hz (Arns, Swatzyna, Gunkelman, & Olbrich, 2015; Morrow et al., 2025). This presentation is distinctly different from the typical irregular beta activity associated with normal cognitive arousal or medication effects. This spindling excessive beta examples is courtesy of Dr. Ronald Swatzyna, Houston Neuroscience Brain Center.

Spindling excessive beta represents cortical hyperexcitability and thalamocortical disruption driven by inflammatory stress. Morrow and colleagues (2025) analyzed EEGs from 1,233 patients with refractory psychiatric conditions and found that spindling excessive beta was present in approximately 25% of the total clinical cohort. The prevalence was particularly striking in adults with traumatic brain injury (TBI), reaching nearly 78%, compared with 31.5% in adults without a TBI history (Morrow et al., 2025).

Topographical analysis provides further clinical insight. Patients without TBI typically showed spindling excessive beta concentrated in frontal and central regions, while patients with TBI exhibited a shift toward heavy temporal concentration, aligning with the known biomechanical vulnerabilities of temporal lobes during head trauma (Morrow et al., 2025; Schimmel, Acosta, & Lozano, 2017). In statistical models, right-lateralized electrodes predicted TBI group membership with 85.1% classification accuracy (Morrow et al., 2025).

Identifying this biomarker can significantly alter the treatment trajectory. Relying solely on symptom-driven diagnoses can lead to counterproductive pharmaceutical choices; for example, prescribing selective serotonin reuptake inhibitors for anxiety can exacerbate beta activity and worsen the spindling excessive beta pattern in inflamed patients (Swatzyna et al., 2024).

Interventions such as guanfacine combined with N-acetylcysteine, photobiomodulation, and hyperbaric oxygen therapy show greater clinical promise in normalizing these patterns by targeting cellular perfusion and inflammation (Gottfried, Schottlender, & Ashery, 2021; Morrow et al., 2025).

Where Heart Disease and Alzheimer’s Disease Meet

The bridge between coronary disease and Alzheimer’s disease is not shared age alone. Shared genetic architecture and reduced cerebral perfusion, meaning reduced blood flow through brain tissue, both connect cardiovascular biology to dementia risk (Koskeridis et al., 2024; Wolters et al., 2017).

Blood pressure control illustrates the practical value of that bridge. In SPRINT MIND, intensive treatment reduced mild cognitive impairment and the combined outcome of mild cognitive impairment or probable dementia, while companion magnetic resonance imaging work showed slower progression of white-matter lesions (Nasrallah et al., 2019; Williamson et al., 2019). Later follow-up supported persistent cognitive benefit (Reboussin et al., 2025).

FINGER pointed in the same direction with different tools. A multidomain intervention combining diet, exercise, cognitive training, and vascular risk monitoring preserved or improved cognition in at-risk older adults (Ngandu et al., 2015). The most available anti-inflammatory strategy for the aging brain remains excellent vascular medicine.

Glucose stability belongs in that same preventive frame. No evidence justifies presenting glucose control as an Alzheimer-specific therapy, but reducing repeated glycemic excursions is a reasonable way to lower shared microvascular, inflammatory, and perfusion-related stress across heart, kidney, retina, and brain (Ceriello et al., 2008; Habte-Asres et al., 2022; Watt et al., 2020).

Applying This in Clinical Practice

For cardiovascular prevention, hs-CRP is most useful when risk decisions are uncertain or when residual risk remains despite apparently good LDL control (Arnett et al., 2019; Mensah et al., 2025; Virani et al., 2023). For autonomic assessment, a short resting HRV recording with attention to LnVLF can provide a physiological readout of whether the cholinergic anti-inflammatory pathway is functioning (Shaffer & Ginsberg, 2017). For refractory psychiatric presentations, a routine quantitative EEG to screen for spindling excessive beta may redirect treatment away from medications that worsen cortical hyperexcitability (Morrow et al., 2025; Swatzyna et al., 2024).

For dysglycemia, the practical question is often whether the numbers and the tissues agree. When fatigue after meals, suspected reactive hypoglycemia, obesity with insulin resistance, retinopathy, kidney disease, or neuropathic symptoms seem disproportionate to fasting glucose or HbA1c, a 10- to 14-day CGM trial can reveal the actual pattern (Battelino et al., 2019; Bergman et al., 2020). That is especially useful when chronic kidney disease weakens the agreement between HbA1c and day-to-day glycemia (Ling et al., 2022).

The first goal is not to chase every excursion but to identify recurring triggers. CGM often shows variability clustering around carbohydrate-heavy breakfasts, large refined-carbohydrate meals eaten without much protein or fiber, prolonged sitting after meals, and irregular sleep timing (Shen et al., 2025; Zahalka et al., 2024).

Several behaviors have an unusually strong signal. Eating non-starchy vegetables and protein before starch can blunt postprandial excursions, a higher-protein breakfast can reduce glucose rises across the day, and post-meal walking lowers postprandial glucose more reliably than waiting until later (Engeroff et al., 2023; Shukla et al., 2017; Xiao et al., 2022). In adults with type 2 diabetes who are not taking insulin, randomized and meta-analytic evidence suggests that CGM, paired with food and lifestyle guidance, can improve glycemic metrics and body weight (Bannuru et al., 2025; Martens et al., 2025).

The caution on the neuropsychiatric side is equally important. Neither CRP nor CGM should be presented as an Alzheimer’s diagnostic test, and currently available anti-inflammatory drugs should not be prescribed as routine Alzheimer’s therapy outside established indications or trials (Aisen et al., 2003; Darweesh et al., 2018; Meyer et al., 2019). For clinical psychologists and counselors, the integrative stance is to collaborate with medical colleagues when these biomarkers are abnormal rather than to reframe symptom-based diagnoses in isolation.

Integrative Summary

Inflammation is not incidental background noise. In heart disease it is now a clinically actionable driver, in Alzheimer’s disease it is a biologically central but therapeutically unresolved process, and in refractory psychiatric presentations it is an under-recognized contributor that can be partly read through HRV and EEG (Heneka et al., 2013; Mensah et al., 2025; Morrow et al., 2025). Glucose variability may be one of the metabolic ways vascular and neural inflammation are fed between clinic visits.

The practical synthesis for healthcare providers is straightforward. Treat lipids and blood pressure well, look for residual inflammatory risk with hs-CRP, use HRV to monitor vagal tone, consider quantitative EEG when psychiatric presentations resist standard care, stop trusting averages alone when the phenotype says otherwise, and use CGM selectively to reduce recurrent glucose excursions that may be stressing retina, kidney, heart, and brain at the same time (Battelino et al., 2019; Reboussin et al., 2025; Shaffer & Ginsberg, 2017; Watt et al., 2020).

Five Takeaways

First, atherosclerosis is both lipid disease and immune disease. Cholesterol retention and chronic innate immune activation are now inseparable parts of the same pathologic process.

Second, three biomarkers triangulate systemic inflammation for clinical decision-making. High-sensitivity C-reactive protein indexes peripheral immune activation, suppressed LnVLF on HRV signals vagal withdrawal and loss of parasympathetic inflammatory control, and spindling excessive beta on EEG can reveal neuroinflammation that mimics standard psychiatric illness.

Third, glucose variability is a plausible inflammatory amplifier even when average glycemia looks acceptable. Repeated swings appear capable of damaging vascular tissue and stressing the brain through oxidative and inflammatory mechanisms.

Fourth, Alzheimer’s disease clearly involves neuroinflammation, but routine anti-inflammatory pharmacotherapy is not ready. The biology is strong, while broad drug trials have been disappointing, so vascular and metabolic prevention remains the most actionable anti-inflammatory strategy for the aging brain.

Fifth, the most practical heart-brain strategy integrates disciplined vascular medicine, autonomic and cortical biomarker screening, and glucose stability. Blood pressure control, lifestyle intervention, HRV- and EEG-informed psychiatric care, and reduction of recurrent glucose spikes are the most useful tools available now.

Glossary

amyloid-β: a peptide derived from amyloid precursor protein that can aggregate into plaques and provoke glial and vascular responses in Alzheimer’s disease.

atherosclerosis: a chronic arterial disease in which lipids, inflammatory cells, fibrous tissue, and necrotic debris accumulate within the vessel wall.

blood-brain barrier: the specialized vascular interface that regulates movement of cells, molecules, and ions between blood and brain tissue.

cholinergic anti-inflammatory pathway: a vagal reflex in which efferent parasympathetic signaling inhibits cytokine production in the spleen and other organs.

continuous glucose monitoring (CGM): a method of measuring interstitial glucose at frequent intervals to reveal patterns that spot checks and averages can miss.

C-reactive protein (CRP): an acute-phase protein produced by the liver in response to inflammatory cytokines, used clinically as a primary marker of systemic immune activation.

cytokine: an immune signaling protein that helps start, amplify, or resolve inflammation.

dysglycemia: any abnormality in blood glucose regulation, encompassing both elevated and reduced glucose levels outside normal physiological ranges.

electroencephalography (EEG): a technique that records scalp electrical activity of the brain, used clinically to evaluate cortical function.

endothelium: the thin cell layer lining blood vessels that regulates permeability, vascular tone, clotting, and immune cell traffic.

glucose variability: the magnitude and frequency of glucose fluctuation around the mean across hours and days.

heart rate variability (HRV): the beat-to-beat temporal fluctuation in heart rhythm, used as a non-invasive index of autonomic function and vagal tone. hemoglobin A1c (HbA1c): a blood test that reflects average blood glucose levels over the previous 2-3 months by measuring the percentage of hemoglobin molecules with glucose attached.

high-sensitivity C-reactive protein (hs-CRP): a sensitive assay for CRP used to detect low-grade systemic inflammation relevant to cardiovascular and neuropsychiatric risk.

hyperbaric oxygen therapy: a therapeutic modality providing oxygen at higher-than-atmospheric pressures to enhance tissue oxygenation and reduce systemic inflammatory markers.

inflammasome: an intracellular danger-sensing complex that activates inflammatory mediators such as interleukin-1β.

LnVLF: the natural log of very low frequency power in heart rate variability, reflecting parasympathetic outflow, thermoregulation, and renin-angiotensin activity.

mean amplitude of glycemic excursions (MAGE): a summary measure of major upward and downward glucose swings over time.

microglia: the resident immune cells of the central nervous system that coordinate inflammatory responses to protect against acute trauma or pathogens.

neuroinflammation: an immune-mediated inflammatory process within the brain or spinal cord that is protective acutely but neurologically harmful when chronically activated.

oxidative stress: excess production of reactive oxygen species that damages cellular structures and signaling.

pericyte: a support cell wrapped around capillaries that helps maintain microvascular stability and blood-brain barrier integrity.

photobiomodulation: a therapeutic modality using red or near-infrared light to stimulate cellular repair mechanisms and lower inflammation in neural tissues.

postprandial: occurring after a meal. It's commonly used in medical and physiological contexts, as in postprandial blood glucose (blood sugar measured after eating) or postprandial hypotension (a drop in blood pressure following a meal).

residual inflammatory risk: persisting cardiovascular risk linked to inflammation despite treatment of conventional risk factors such as LDL cholesterol.

spindling excessive beta: an EEG pattern featuring sinusoidal, spindle-like waves between 13 and 35 Hz strongly associated with neuroinflammatory states.

tau: a neuronal protein that can misfold and aggregate into neurofibrillary tangles in Alzheimer’s disease.

time in range (TIR): the percentage of continuous glucose monitoring readings spent within a predefined glucose target range.

vagal withdrawal: a clinical state of suppressed parasympathetic signaling, reflected in reduced HRV and loss of cholinergic restraint on inflammation.

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About the Author

Fred Shaffer earned his PhD in Psychology from Oklahoma State University. He earned BCIA certifications in Biofeedback and HRV Biofeedback. Fred is an Allen Fellow and Professor of Psychology at Truman State University, where he has taught for 50 years. He is a Biological Psychologist who consults and lectures in heart rate variability biofeedback, Physiological Psychology, and Psychopharmacology. Fred helped to edit Evidence-Based Practice in Biofeedback and Neurofeedback (3rd and 4th eds.) and helps to maintain BCIA's certification programs. He is a recipient of AAPB's Distinguished Scientist Award and BFE's Lifetime Impact Award.