What Tests Can Identify the Root Cause of Brain Fog?

Last Updated: November 2025


Brain with scrabbled question marks for blog about root of cause for brain fog. Image used by Dr. Jessica Knape of HealthSpan Internal Medicine in Boulder, CO.jpg

In this FAQ, Dr. Jessica Knape of HealthSpan Internal Medicine in Boulder, CO, explains that brain fog is a signal of underlying imbalances, not a diagnosis. By using comprehensive testing to uncover contributors like inflammation, hormonal shifts, toxins, infections, and sleep issues, she helps patients reverse fog and restore clarity.

Brain fog is a message — not a diagnosis.
It’s your brain’s way of saying that its energy, oxygen, hormones, or communication systems need support.
At HealthSpan Internal Medicine in Boulder, CO, we use a comprehensive, evidence-based approach to identify why fog is happening so we can reverse it.

Because brain fog has many potential contributors — inflammation, hormones, toxins, infections, mitochondria, sleep problems, gut issues — the right testing makes all the difference.

HealthSpan Insight

  • There is no single “brain fog test.”

  • A root-cause approach evaluates inflammation, hormones, nutrient status, mitochondria, toxins, sleep, and gut health.

  • Most causes are treatable when identified early.

1. Inflammation & Immune Activation Testing

Low-grade inflammation is one of the most common drivers of brain fog. These tests identify whether the immune system is activated or overwhelmed:

• High-sensitivity CRP (hs-CRP)
Shows systemic inflammation; even mild elevations may impair cognition.

• ESR (erythrocyte sedimentation rate)
Measures chronic inflammatory activity.

• Ferritin
High ferritin can signal chronic inflammation. Low ferritin suggests iron deficiency, which also causes fog.

• Cytokine markers (IL-6, TNF-α)
Useful in chronic infections, long-COVID patterns, mold illness, and autoimmune activation.

2. Thyroid & Hormone Testing

Hormones act like the brain’s communication network. Even small imbalances can cause fog, slow thinking, or mood changes.

Thyroid panel

  • TSH

  • Free T4

  • Free T3

  • Reverse T3

  • Thyroid antibodies

Low T3, even with a normal TSH, can cause profound cognitive slowing.

Sex hormones

  • Progesterone: calming, neuroprotective

  • Testosterone: motivation, speed, word recall

  • Estradiol: synaptic plasticity, blood flow

  • DHEA: mood, energy

Cortisol (AM + PM pattern or 4-point adrenal curve)
Both high and low cortisol impair focus, sleep, and memory.

3. Metabolic & Blood Sugar Evaluation

Blood sugar swings, insulin resistance, and low glucose delivery to the brain are major fog triggers.

Important labs include:

  • Fasting glucose

  • Insulin

  • HOMA-IR (insulin resistance)

  • Hemoglobin A1c

  • Lipid profile

Patients with insulin resistance often describe their brain fog as “crashing,” “spacey,” or “unable to access words.”

4. Nutrient Testing for Cognitive Performance

Several nutrients are essential for methylation, neurotransmitters, mitochondrial function, and myelination.

Key labs:

• Vitamin B12 and methylation markers

  • B12

  • MMA (methylmalonic acid)

  • Homocysteine

  • Folate
    Deficiency is extremely common in older adults and causes memory issues, fog, tingling, and fatigue.

• Vitamin D

Low levels contribute to immune dysfunction and low mood.

• Omega-3 Index

Identifies whether the brain has adequate anti-inflammatory fats.

• Magnesium RBC

Magnesium threonate is especially helpful for cognition.

• Iron panel

Iron deficiency reduces oxygen delivery to the brain.

5. Mitochondrial & Oxidative Stress Testing

Brain fog often reflects low ATP production (cellular energy).
We evaluate:

  • Organic acids test (OAT)
    Assesses mitochondrial function, neurotransmitter metabolites, and oxidative stress.

  • CoQ10 levels
    Low in statin users and older adults.

  • Lactate/pyruvate ratio
    Useful in persistent post-viral or post-concussion fatigue.

Mitochondrial support (light therapy, oxygen therapy, methylene blue, CoQ10, carnitine) often lifts fog dramatically.

6. Gut & Microbiome Testing

Because the gut and brain share immune, hormonal, and neurological pathways, gut dysfunction is one of the most overlooked causes of brain fog.

We may use:

• Comprehensive stool microbiome analysis
Assesses dysbiosis, leaky gut, inflammation, enzyme function, SCFA production.

• Zonulin or permeability markers
Identify intestinal barrier breakdown.

• SIBO breath test
Gas patterns (hydrogen, methane, hydrogen sulfide) correlate with fog, bloating, fatigue, and mood.

• Food sensitivity panels
Identify immune activation patterns.

7. Environmental Toxin Testing

Toxins can impair mitochondria, hormones, and neural signaling.

Common panels include:

  • Mycotoxin testing (mold toxins)

  • Heavy metals (mercury, lead, arsenic, cadmium)

  • Chemical exposures (pesticides, VOCs, plastics metabolites)

Patients with mold exposure often experience “unreachable thoughts,” slow word recall, and morning fog.

8. Infectious & Immune Trigger Evaluation

Chronic infections sometimes present primarily as brain fog, fatigue, and mood changes.

Targeted tests include:

  • EBV reactivation panel

  • Lyme and co-infections

  • CMV

  • Mycoplasma pneumoniae

  • Post-COVID inflammation markers

These aren’t needed for everyone — only when history and symptoms match.

9. Sleep & Oxygenation Testing

Poor sleep and low oxygen delivery to the brain are extremely common — and reversible — causes of fog.

• Home sleep study

Identifies sleep apnea, snoring, oxygen drops, and disrupted deep sleep.

• Overnight pulse oximetry

Screens for subtle hypoxia.

• Actigraphy

Evaluates sleep cycles and circadian rhythm.

Untreated sleep apnea is one of the leading reversible causes of cognitive decline.

10. Neurologic Testing When Needed

If red flags are present (imbalance, memory loss, tremors, headaches), neurologic evaluation may include:

  • MRI with volumetrics
    Shows patterns of atrophy or inflammation.

  • Cognitive testing (MoCA or CNS Vital Signs)
    Detects early impairment.

  • EEG or qEEG
    Useful for post-concussion or seizure-related fog.

These are rarely first-line but important when neurological disease is suspected.

11. How HealthSpan Integrates These Results

We interpret labs through a whole-systems lens:

  • Energy: mitochondria, oxygen, nutrients

  • Inflammation: immune, gut, toxins

  • Communication: hormones, neurotransmitters, vagus nerve

  • Structure: sleep, movement, circulation

By finding the pattern — not just the number — we can design personalized Brainspan™ plans that restore clarity and prevent decline.

Bottom Line

Brain fog is common — but it’s not “normal aging.”
It’s a signal that something in the body-brain network needs attention.

Using functional testing, we can identify whether the root cause is inflammation, hormones, mitochondria, circulation, toxins, gut health, sleep, or a combination.
Most causes are treatable, and early intervention protects long-term brain health.

At HealthSpan Internal Medicine in Boulder, CO, we use advanced diagnostics and personalized care to restore clarity, focus, and cognitive resilience.

If you’ve been told “your labs are fine” but you still feel foggy, tired, or unfocused, it’s time for a deeper look.
Dr. Knape blends clinical experience with advanced biomarkers and functional testing to uncover hidden contributors to brain fog.
👉 Schedule your evaluation.

Sources

🧠 Inflammation, Immune Dysregulation & Cognitive Symptoms

Marsland AL et al., Brain, Behavior, and Immunity, 2017 — PMC
Shows how systemic inflammation and cytokines (CRP, IL-6, TNF-α) impair memory and executive function, supporting the use of inflammatory biomarkers in evaluating brain fog.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6404203/

🧬 Metabolic Dysfunction, Insulin Resistance & Cognitive Decline

Ekblad LL et al., Diabetes Care, 2017 — PMC
Demonstrates that insulin resistance and impaired glucose metabolism are strongly linked to brain fog, reduced cognition, and early Alzheimer’s changes. Supports ordering fasting insulin, HbA1c, glucose, lipids, and HOMA-IR.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC5654383/

⚡ Thyroid Dysfunction & Cognitive Impairment

Taylor PN et al., Lancet Diabetes & Endocrinology, 2018 — PMC
A major review showing that both hypothyroidism and hyperthyroidism contribute to memory problems, slowed processing, and cognitive fog—supporting testing TSH, free T3, free T4, TPO antibodies.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC5869486/

🌿 Hormonal Changes (Estrogen, Progesterone, Testosterone) & Brain Fog

Barth C et al., Frontiers in Neuroendocrinology, 2015 — PMC
Explains how sex hormone fluctuations affect memory, attention, and clarity. Reinforces the role of comprehensive hormone testing during perimenopause, menopause, and andropause.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC5014523/

🔬 Gut–Brain Axis, Microbiome & Cognitive Symptoms

Cryan JF et al., Physiological Reviews, 2019 — PMC
A definitive review linking gut dysbiosis, intestinal permeability, and microbial metabolites to cognitive symptoms and brain fog—supporting tests such as GI-MAP, stool analysis, zonulin, and microbiome assessments.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6775482/

Medically reviewed by
Dr. Jessica Knape, MD, MA Board Certified in Internal Medicine and Integrative and Holistic Medicine
Healthspan Internal Medicine — serving patients in Boulder, CO

Book a Discovery Call | About Dr. Knape

This content is for educational purposes and does not replace personalized medical advice.

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