This protocol was developed for practitioners using Fullscript in the United States and the templates cannot be applied to accounts operating outside of the United States

Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through D-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 

Introduction

What Is Cognitive Support for Healthy Aging?

Cognitive health encompasses the capacity to maintain attention, memory, and mental clarity by supporting the systems that influence brain function. These include mitochondrial efficiency, antioxidant capacity, inflammation balance, adequate nutrient status, and circadian rhythm alignment. (Jost 2025)(Melzer 2021)(Wright 2015) 

This clinical guide emphasizes proactive, measurable approaches that specifically target the immune system to help sustain optimal brain performance and overall vitality across the aging process.

Why Immune Function Matters

The brain and immune system are in constant, bidirectional communication. This dialogue occurs through cytokines, resident immune cells, and vascular signaling at the blood-brain barrier. (Müller 2025) Under healthy conditions, this cross-talk supports synaptic maintenance, debris clearance, neuroplasticity, and neuronal survival. When immune signaling becomes dysregulated, the same pathways can promote chronic neuroinflammation, synaptic loss, and progressive cognitive decline. (Zhao 2022)

Age-related immune remodeling, known as immunosenescence, is characterized by a deterioration of the immune system and low-grade inflammation (“inflammaging”). This process is driven by factors such as infections, environmental exposures, dysbiosis, and unhealthy lifestyle habits. (Liu 2023) Over time, this age-related inflammatory cascade compromises cognitive performance and contributes to neurodegeneration. (Barbé-Tuana 2020)

Purpose of the Clinical Guide

The Immune Health as a Root Driver clinical guide was designed to:

    1. Simplify decision-making using standardized, evidence-rated nutrient interventions.
    2. Integrate laboratory and biomarker data to identify modifiable immunological contributors to cognitive health.
    3. Complement the Cognitive Essentials for Healthy Aging clinical guide, enabling providers to integrate immune-focused strategies alongside foundational interventions.

Essential Labs

Immune Markers

Evidence points to a network of immune-derived indices that indicate an “inflammaging” phenotype associated with poorer cognitive outcomes. (Wang 2022) 

Complete Blood Count 

White Blood Cell (WBC) Count

WBC counts (leukocytosis) (>11,000 per mm3) are independently associated with increased risk of cognitive decline and dementia in both Alzheimer’s and Parkinson’s disease. Leukocytosis has been identified as a risk factor for Parkinson’s dementia and is linked to mechanisms underlying cognitive dysfunction, suggesting that systemic inflammation may accelerate neurodegeneration. (Unda 2021) Higher WBC counts are also inversely associated with brain volume and markers of advanced brain aging, with magnetic resonance imaging (MRI) studies showing that elevated WBCs correlate with accelerated brain atrophy patterns observed in dementia. (Janowitz 2020)

Systemic Immune-Inflammation Index (SII)

The SII is calculated using the formula SII = (platelet count × neutrophil count) / lymphocyte count. This index reflects the interaction between inflammatory activity, represented by neutrophils and platelets, and immune regulation, represented by lymphocytes. Elevated SII levels indicate systemic inflammation, which has been associated with cognitive impairment and an increased risk of neurodegenerative disease. (Wang 2025)

Systemic Inflammation Response Index (SIRI)

The SIRI is calculated using the formula SIRI = (neutrophil count × monocyte count) / lymphocyte count. This index represents the balance between innate immune activation, driven by neutrophils and monocytes, and adaptive immune defense, mediated by lymphocytes. Higher SIRI values indicate a greater systemic inflammatory burden, which may contribute to cognitive decline and the progression of chronic diseases. Overall, SIRI provides a simple and accessible biomarker for assessing inflammation-related cognitive risk. (Wang 2025)

Neutrophil-Lymphocyte Ratio (NLR)

The NLR is a marker of systemic inflammation derived from standard complete blood count (CBC) results. In a meta-analysis, a high NLR was associated with a significantly greater risk of cognitive impairment (OR 2.53, 95% CI 1.67–3.82, p < 0.0001). (Hung 2023)

Specialty Labs

Toxin Panel 

Environmental toxicants—including heavy metals (lead, aluminum, mercury, manganese, cadmium, arsenic), pesticides, solvents, and airborne particulates—are increasingly recognized as contributors to neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. These agents promote key pathological features, including amyloid plaques and neurofibrillary tangles, through mechanisms involving protein aggregation, oxidative stress, chronic neuroinflammation, and disruption of neurotransmission. (Nabi 2022)

Blood and urine are the most widely accepted specimens for assessing heavy metal exposure, with the detection window varying by toxin and specimen, while bone and hair reflect longer-term or cumulative exposures. For pesticides and solvents, testing typically targets specific metabolites, and detection windows are short because these compounds are rapidly metabolized and excreted. (Klimowska 2020)(Lamas 2023)

Lyme Testing

Lyme disease is a tick-transmitted bacterial infection caused primarily by Borrelia burgdorferi that can spread beyond its initial flu-like symptoms to affect the nervous system, a condition known as neuroborreliosis. In some cases, especially when treatment is delayed, Borrelia can invade the central nervous system and trigger neuroinflammation, which may disrupt cognitive processes such as memory, attention, and processing speed. Blood tests may help determine a patient’s immune response to infection and stage of Lyme disease. (Touradji 2019)(Berende 2019)

Comprehensive Stool Analysis 

Specialty stool testing can highlight alterations in gut microbial diversity, short-chain fatty acid (SCFA) production, and intestinal barrier integrity—factors increasingly associated with neurodegenerative disease risk. 

In Alzheimer’s cohorts, reduced diversity and lower abundance of butyrate-producing bacteria have been linked to greater neuroinflammation and diminished neuroprotection. (Vogt 2017) Alzheimer’s-spectrum patients also show shifts in microbial genera across Firmicutes, Bacteroidetes, and Proteobacteria, reinforcing the association between microbial dysbiosis and neurodegenerative disease processes. (Hung 2022)

Elevated gut permeability markers such as zonulin further suggest a role for systemic immune activation in accelerating cognitive decline. (Boschetti 2023)

Ingredients

Beta-Glucan

Dosing: 250–500 mg daily for 4–12 weeks (Muroya 2025)

Supporting evidence:

  • A meta-analysis of 16 randomized controlled trials (RCTs) with 1,449 participants found that yeast beta-glucan reduces fatigue and improves antioxidant/immune markers. (Muroya 2025)
  • Beta-glucan primes innate immune cells for stronger antimicrobial and inflammatory responses. (Zhong 2023) It acts as an adjuvant, enhancing the effects of natural or therapeutic antibodies. (Vetvicka 2019)
  • Short-term beta-glucan supplementation can increase salivary immunoglobulin A (IgA) levels, and support mucosal immune defenses in people experiencing physical or psychological stress. (Vetvicka 2019)

Lithium

Dosing: 150–300 µg daily for 15 months (Nunes 2013) 

Supporting evidence: 

  • In patients with AD, microdosing lithium at 300 µg/day for 15 months appeared to stabilize cognitive function compared with controls, as evidenced by the absence of decline in Mini-Mental State Examination (MMSE) scores, with statistically significant differences emerging as early as three months. (Nunes 2013)
  • In a two-year randomized, double-blind, placebo-controlled trial of 61 older adults with amnestic mild cognitive impairment (MCI), long-term low-dose lithium carbonate (0.25–0.5 mEq/L serum concentration) stabilized cognitive and functional performance, while the placebo group showed progressive decline. Lithium treatment improved memory and attention and increased cerebrospinal fluid amyloid-beta 42 (Aβ42) concentrations after 36 months, suggesting a disease-modifying effect in the MCI-to-AD continuum. (Forlenza 2019)
  • Lithium is an essential trace element involved in cellular signaling and neuroprotection. Recent research suggests that endogenous brain lithium plays a physiological role in maintaining synaptic plasticity by reducing neuroinflammation via inhibition of glycogen synthase kinase-3 (GSK-3). (Aron 2025)(Szałach 2023) 
  • In post-mortem studies, brain lithium levels were significantly lower in individuals with MCI and AD. Experimental depletion of lithium in mice increased amyloid-β deposition, tau phosphorylation, neuroinflammation, and cognitive decline. Conversely, lithium orotate replacement prevented these pathological changes and preserved memory. (Aron 2025)

Phosphatidylserine (PS)

Dosing: 300–500 mg per day for 3 weeks to 6 months (Ma 2022)(Richter 2013) 

Supporting evidence:

  • PS is a key phospholipid in neuronal membranes and may support cognition by influencing neurotransmitter systems, neuronal signaling, and membrane integrity. (Richter 2013)
  • PS modulates immune processes toward a neuroprotective phenotype by reducing pro-inflammatory cytokine production, enhancing anti-inflammatory signaling, and influencing microglial activity in ways that support synaptic integrity and cognitive function. (Ma 2022)
  • In a pilot trial of elderly adults with memory complaints, 300 mg/day of soybean-derived PS for 12 weeks significantly improved memory recognition, recall, executive function, and mental flexibility compared to baseline, without serious adverse events. (Richter 2013)
  • A double-blind, placebo-controlled trial in 78 elderly Japanese adults with memory complaints found that soy-derived PS (100–300 mg/day for 6 months) helped improve memory, particularly delayed verbal recall, and primarily in participants with lower baseline performance. Benefits were maintained after supplementation ended. (Kato-Kataoka 2010)

L-Theanine

Dosing: 100–400 mg per day as needed or continuously for 4 weeks (Baba 2021)(Dassanayake 2022)(Dassanayake 2023)(Hidese 2019)

Supporting evidence:

  • L-theanine, an amino acid found in green tea, can enhance the function of certain T lymphocytes and may modulate glutamate receptors and neurotransmitters, thereby supporting stress reduction, improved sleep quality, and enhanced cognition. (Hidese 2019)(Chen 2023)
  • In a randomized, double-blind, placebo-controlled crossover trial with 30 healthy adults, 200 mg/day for 4 weeks reduced stress and anxiety scores, improved sleep quality, and enhanced verbal fluency and executive function, with greater effects in those with lower baseline scores. (Hidese 2019)
  • In acute dosing studies, 100–400 mg of L-theanine improved reaction time in simple visuomotor tasks (100–200 mg) and reduced P3b latency in an auditory attention task in a dose-dependent manner (400 mg), indicating enhanced attentional processing. (Dassanayake 2022)(Dassanayake 2023)
  • Evidence from a 12-week randomized, double-blind, placebo-controlled trial in older adults demonstrated that L-theanine supplementation (100 mg/day) was associated with the preservation of cognitive flexibility, a slowed decline in executive function, and a reduction in inflammatory markers. (Baba 2021)

Rhodiola (Rhodiola rosea)

Dosing: 170–576 mg of standardized extract SHR-5 (3% rosavins, 1% salidroside) for 14–28 days (Darbinyan 2000)(Koop 2020)(Olsson 2009)

Supporting evidence:

  • Rhodiola rosea is an adaptogenic herb thought to reduce fatigue and improve cognitive performance by modulating stress-response pathways, neurotransmitters, and cortisol secretion. (Darbinyan 2000)(Olsson 2009) Studies have demonstrated that interventions that reduce stress and cortisol are associated with improvements in immune and inflammatory biomarkers. (Lee 2025)
  • In a double-blind, crossover trial involving 56 young physicians on night duty, repeated low-dose SHR-5 (daily for 2 weeks) significantly improved mental performance measures, including short-term memory, associative thinking, calculation, concentration, and perceptual speed, compared with placebo, with no reported side effects. (Darbinyan 2000)
  • In a 28-day randomized, double-blind, placebo-controlled trial of 60 adults with stress-related fatigue, SHR-5 (576 mg/day) significantly improved fatigue scores, attention (fewer omissions and greater response stability), and normalized cortisol awakening response compared with placebo, suggesting benefits for concentration and stress resilience. (Olsson 2009)
  • In a 12-week open-label study of 50 adults, 400 mg/day of rhodiola extract improved reaction times and increased P3 amplitude on event-related potentials, suggesting enhanced mental speed and resource allocation. (Koop 2020)

Boron

Dosing: 6–10 mg daily for one week (Pizzorno 2015) 

Supporting evidence: 

  • Boron is a trace mineral that appears to protect against oxidative stress by upregulating endogenous antioxidant enzymes. It also exhibits anti-inflammatory effects, as evidenced by associations with lower levels of inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). (Pizzorno 2015)
  • Boron supplementation is associated with improved immune and central nervous system function. Low boron status has been related with poor immune function, impaired cognitive performance, and cognitive deterioration. (Khaliq 2018)(Bartusik-Aebisher 2025)

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References

References

  1. Algul, F. E., & Kaplan, Y. (2025). Increased systemic immune-inflammation index as a novel indicator of Alzheimer’s disease severity. Journal of Geriatric Psychiatry and Neurology, 38(3), 214–222. https://doi.org/10.1177/08919887241280880
  2. Aron, L., Ngian, Z. K., Qiu, C., Choi, J., Liang, M., Drake, D. M., Hamplova, S. E., Lacey, E. K., Roche, P., Yuan, M., Hazaveh, S. S., Lee, E. A., Bennett, D. A., & Yankner, B. A. (2025). Lithium deficiency and the onset of Alzheimer’s disease. Nature, 645(8081), 712–721. https://doi.org/10.1038/s41586-025-09335-x
  3. Baba, Y., Inagaki, S., Nakagawa, S., Kaneko, T., Kobayashi, M., & Takihara, T. (2021). Effects of L-theanine on cognitive function in middle-aged and older subjects: A randomized placebo-controlled study. Journal of Medicinal Food, 24(4), 333–341. https://doi.org/10.1089/jmf.2020.4803
  4. Barbé-Tuana, F., Funchal, G., Schmitz, C. R. R., Maurmann, R. M., & Bauer, M. E. (2020). The interplay between immunosenescence and age-related diseases. Seminars in Immunopathology, 42(5), 545–557. https://doi.org/10.1007/s00281-020-00806-z
  5. Bartusik-Aebisher, D., Rudy, I., Rogóż, K., Aebisher, D., & Henrykowska, G. (2025). Boron in diet and medicine: Mechanisms of delivery and detection. Pharmaceuticals (Basel, Switzerland), 19(1), 81. https://doi.org/10.3390/ph19010081
  6. Berende, A., Agelink van Rentergem, J., Evers, A. W. M., Ter Hofstede, H. J. M., Vos, F. J., Kullberg, B. J., & Kessels, R. P. C. (2019). Cognitive impairments in patients with persistent symptoms attributed to Lyme disease. BMC infectious diseases, 19(1), 833. https://doi.org/10.1186/s12879-019-4452-y
  7. Boschetti, E., Caio, G., Cervellati, C., Costanzini, A., Rosta, V., Caputo, F., De Giorgio, R., & Zuliani, G. (2023). Serum zonulin levels are increased in Alzheimer’s disease but not in vascular dementia. Aging Clinical and Experimental Research, 35(9), 1835–1843. https://doi.org/10.1007/s40520-023-02463-2
  8. Chen, S., Kang, J., Zhu, H., Wang, K., Han, Z., Wang, L., Liu, J., Wu, Y., He, P., Tu, Y., & Li, B. (2023). L-Theanine and immunity: A review. Molecules (Basel, Switzerland), 28(9), 3846. https://doi.org/10.3390/molecules28093846
  9. Darbinyan, V., Kteyan, A., Panossian, A., Gabrielian, E., Wikman, G., & Wagner, H. (2000). Rhodiola rosea in stress induced fatigue–A double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 7(5), 365–371. https://doi.org/10.1016/S0944-7113(00)80055-0
  10. Dassanayake, T. L., Kahathuduwa, C. N., & Weerasinghe, V. S. (2022). L-theanine improves neurophysiological measures of attention in a dose-dependent manner: A double-blind, placebo-controlled, crossover study. Nutritional Neuroscience, 25(4), 698–708. https://doi.org/10.1080/1028415x.2020.1804098
  11. Dassanayake, T. L., Wijesundara, D., Kahathuduwa, C. N., & Weerasinghe, V. S. (2023). Dose–response effect of L-theanine on psychomotor speed, sustained attention, and inhibitory control: A double-blind, placebo-controlled, crossover study. Nutritional Neuroscience, 26(11), 1138–1146. https://doi.org/10.1080/1028415x.2022.2136884
  12. Forlenza, O. V., Radanovic, M., Talib, L. L., & Gattaz, W. F. (2019). Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. British Journal of Psychiatry, 215(5), 668–674. https://doi.org/10.1192/bjp.2019.76
  13. Hidese, S., Ogawa, S., Ota, M., Ishida, I., Yasukawa, Z., Ozeki, M., & Kunugi, H. (2019). Effects of L-theanine administration on stress-related symptoms and cognitive functions in healthy adults: A randomized controlled trial. Nutrients, 11(10), 2362. https://doi.org/10.3390/nu11102362
  14. Hung, C.-C., Chang, C.-C., Huang, C.-W., Nouchi, R., & Cheng, C.-H. (2022). Gut microbiota in patients with Alzheimer’s disease spectrum: A systematic review and meta-analysis. Aging, 14(1), 477–496. https://doi.org/10.18632/aging.203826
  15. Hung, K.-C., Liu, C.-C., Wu, J.-Y., Ho, C.-N., Lin, M.-C., Hsing, C.-H., & Chen, I-Wen. (2023). Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: A meta-analysis of observational studies. Frontiers in Endocrinology, 14, 1265637. https://doi.org/10.3389/fendo.2023.1265637
  16. Janowitz, D., Habes, M., Toledo, J. B., Hannemann, A., Frenzel, S., Terock, J., Davatzikos, C., Hoffmann, W., & Grabe, H. J. (2020). Inflammatory markers and imaging patterns of advanced brain aging in the general population. Brain Imaging and Behavior, 14(4), 1108–1117. https://doi.org/10.1007/s11682-019-00058-y
  17. Jost, Z., & Kujach, S. (2025). Understanding cognitive decline in aging: Mechanisms and mitigation strategies – A narrative review. Clinical Interventions in Aging, 20, 459–469. https://doi.org/10.2147/cia.s510670
  18. Kato-Kataoka, A., Sakai, M., Ebina, R., Nonaka, C., Asano, T., & Miyamori, T. (2010). Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. Journal of Clinical Biochemistry and Nutrition, 47(3), 246–255. https://doi.org/10.3164/jcbn.10-62
  19. Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological trace element research, 186(1), 31–51. https://doi.org/10.1007/s12011-018-1284-3
  20. Klimowska, A., Amenda, K., Rodzaj, W., Wileńska, M., Jurewicz, J., & Wielgomas, B. (2020). Evaluation of 1-year urinary excretion of eight metabolites of synthetic pyrethroids, chlorpyrifos, and neonicotinoids. Environment International, 145, 106119. https://doi.org/10.1016/j.envint.2020.106119
  21. Koop, T., Dienel, A., Heldmann, M., & Münte, T. F. (2020). Effects of a Rhodiola rosea extract on mental resource allocation and attention: An event‐related potential dual task study. Phytotherapy Research, 34(12), 3287–3297. https://doi.org/10.1002/ptr.6778
  22. Lamas, G. A., Bhatnagar, A., Jones, M. R., Mann, K. K., Nasir, K., Tellez-Plaza, M., Ujueta, F., Navas-Acien, A., American Heart Association Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, Council on Lifestyle and Cardiometabolic Health, Council on Peripheral Vascular Disease, & Council on the Kidney in Cardiovascular Disease. (2023). Contaminant metals as cardiovascular risk factors: A scientific statement from the American Heart Association. Journal of the American Heart Association, 12(13), e029852. https://doi.org/10.1161/jaha.123.029852
  23. Lee, S. C., Tsai, P. H., Yu, K. H., & Chan, T. M. (2025). Effects of mind-body interventions on immune and neuroendocrine functions: A systematic review and meta-analysis of randomized controlled trials. Healthcare (Basel, Switzerland), 13(8), 952. https://doi.org/10.3390/healthcare13080952
  24. Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023). Immunosenescence: molecular mechanisms and diseases. Signal Transduction and Targeted Therapy, 8, 200. https://doi.org/10.1038/s41392-023-01451-2
  25. Ma, X., Li, X., Wang, W., Zhang, M., Yang, B., & Miao, Z. (2022). Phosphatidylserine, inflammation, and central nervous system diseases. Frontiers in Aging Neuroscience, 14, 975176. https://doi.org/10.3389/fnagi.2022.975176
  26. Melzer, T. M., Manosso, L. M., Yau, S., Gil-Mohapel, J., & Brocardo, P. S. (2021). In pursuit of healthy aging: Effects of nutrition on brain function. International Journal of Molecular Sciences, 22(9), 5026. https://doi.org/10.3390/ijms22095026
  27. Müller, L., Di Benedetto, S., & Müller, V. (2025). Neuroimmune dynamics and brain aging: mechanisms and consequences. Frontiers in Aging Neuroscience, 17, 1715045. https://doi.org/10.3389/fnagi.2025.1715045
  28. Muroya, M., Nakada, K., Maruo, K., & Hashimoto, K. (2025). Effects of β-glucans on fatigue: A systematic review and meta-analysis. European Journal of Clinical Nutrition, 79(8), 705–714. https://doi.org/10.1038/s41430-025-01567-4
  29. Nabi, M., & Tabassum, N. (2022). Role of environmental toxicants on neurodegenerative disorders. Frontiers in Toxicology, 4, 837579. https://doi.org/10.3389/ftox.2022.837579
  30. Nunes, M. A., Viel, T. A., & Buck, H. S. (2013). Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Current Alzheimer Research, 10(1), 104–107. https://doi.org/10.2174/1567205011310010014
  31. Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Medica, 75(2), 105–112. https://doi.org/10.1055/s-0028-1088346
  32. Pizzorno, L. (2015). Nothing boring about boron. Integrative Medicine: A Clinician’s Journal, 14(4), 35–48. https://pmc.ncbi.nlm.nih.gov/articles/PMC4712861/
  33. Richter, Y., Herzog, Y., Lifshitz, Y., Hayun, R., & Zchut, S. (2013). The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: A pilot study. Clinical Interventions in Aging, 8, 557–563. https://doi.org/10.2147/cia.s40348
  34. Szałach, Ł. P., Lisowska, K. A., Cubała, W. J., Barbuti, M., & Perugi, G. (2023). The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder. Frontiers in Neuroscience, 17, 1213766. https://doi.org/10.3389/fnins.2023.1213766
  35. Touradji, P., Aucott, J. N., Yang, T., Rebman, A. W., & Bechtold, K. T. (2019). Cognitive decline in post-treatment Lyme disease syndrome. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 34(4), 455–465. https://doi.org/10.1093/arclin/acy051
  36. Unda, S. R., Antoniazzi, A. M., Altschul, D. J., & Marongiu, R. (2021). Peripheral leukocytosis predicts cognitive decline but not behavioral disturbances: A nationwide study of Alzheimer’s and Parkinson’s disease patients. Dementia and Geriatric Cognitive Disorders, 50(2), 143–152. https://doi.org/10.1159/000516340
  37. Vetvicka, V., Vannucci, L., Sima, P., & Richter, J. (2019). Beta glucan: Supplement or drug? From laboratory to clinical trials. Molecules, 24(7), 1251. https://doi.org/10.3390/molecules24071251
  38. Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., Bendlin, B. B., & Rey, F. E. (2017). Gut microbiome alterations in Alzheimer’s disease. Scientific Reports, 7(1), 13537. https://doi.org/10.1038/s41598-017-13601-y
  39. Wang, X., Wen, Q., Li, Y., Zhu, H., Zhang, F., Li, S., Zhan, L., & Li, J. (2025). Systemic inflammation markers (SII and SIRI) as predictors of cognitive performance: Evidence from NHANES 2011-2014. Frontiers in Neurology, 16, 1527302. https://doi.org/10.3389/fneur.2025.1527302
  40. Wang, Y., Dong, C., Han, Y., Gu, Z., & Sun, C. (2022). Immunosenescence, aging and successful aging. Frontiers in Immunology, 13, 942796. https://doi.org/10.3389/fimmu.2022.942796
  41. Wright, K. P. Jr, Drake, A. L., Frey, D. J., Fleshner, M., Desouza, C. A., Gronfier, C., & Czeisler, C. A. (2015). Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain, Behavior, and Immunity, 47, 24–34. https://doi.org/10.1016/j.bbi.2015.01.004
  42. Zhan, Y., Al-Nusaif, M., Ding, C., Li, Z., & Dong, C. (2023). The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies. Frontiers in Neuroscience, 17, 1130730. https://doi.org/10.3389/fnins.2023.1130730
  43. Zhao, F., Li, B., Yang, W., Ge, T., & Cui, R. (2022). Brain–immune interaction mechanisms: Implications for cognitive dysfunction in psychiatric disorders. Cell Proliferation, 55(10), e13295. https://doi.org/10.1111/cpr.13295
  44. Zhong, X., Wang, G., Li, F., Fang, S., Zhou, S., Ishiwata, A., Tonevitsky, A. G., Shkurnikov, M., Cai, H., & Ding, F. (2023). Immunomodulatory effect and biological significance of β-glucans. Pharmaceutics, 15(6), 1615. https://doi.org/10.3390/pharmaceutics15061615