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 inflammation to help sustain optimal brain performance and overall vitality across the aging process.

Why Inflammation Matters

Inflammation is a fundamental biological process that supports immune defense, tissue repair, and cellular homeostasis. However, when inflammatory triggers persist or regulatory mechanisms fail, inflammation becomes chronic, leading to sustained immune activation, excessive cytokine production, and progressive tissue damage. This maladaptive state is a recognized contributor to many chronic diseases and accelerates biological aging processes. (Rossi 2021) 

Neuroinflammation promotes neuronal apoptosis, disrupts synaptic communication, and impairs neurogenesis, particularly in regions critical for memory and learning. Inflammatory signalling also contributes to pathological protein changes that underlie neurodegenerative disease pathology. Together, these processes undermine neural resilience, impair cognitive function, and contribute to cognitive decline. (Mekhora 2024)

Purpose of the Clinical Guide

The Inflammation as a Root Driver for Cognitive Health clinical guide was designed to:

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

Specialty Lab

Fatty15 Test

Pentadecanoic acid (C15:0) is a stable odd-chain saturated fatty acid that strengthens cell membranes against age-related breakdown by targeting upstream drivers of inflammation. (Venn-Watson 2023)(Aabis 2025)(Venn-Watson 2020)(Venn-Watson 2025) Higher C15:0 levels are associated with better cognitive scores, including memory scores among people with type 2 diabetes. (Shen 2022) A C15:0 deficiency can accelerate aging and negatively affect long-term metabolic, heart, and liver health. (Genova Connect n.d.)

Essential Labs

Inflammation Markers

Inflammation markers reflect systemic and neuroinflammatory activity, which has been associated with cognitive decline, slower processing speed, and memory impairments. Elevated inflammatory markers have been linked to structural brain changes and reduced cognitive performance in older adults. (Xie 2022)

High-Sensitivity C-Reactive Protein (hs-CRP)

Higher midlife hs-CRP levels have been associated with greater long-term declines in overall cognition, particularly in memory performance. These findings reflect chronic, low-grade inflammation rather than acute elevations, with elevated hs-CRP indicating inflammatory activity linked to accelerated cognitive decline and increased vulnerability to late-life cognitive impairment. (Walker 2019)

Erythrocyte Sedimentation Rate (ESR)

Higher baseline ESR was linked to faster declines in verbal memory among older men (>50 years), poorer baseline attention performance overall and among African Americans, and reduced verbal fluency in older women (>50 years). Additionally, elevated ESR correlated with executive function impairments across older men, African Americans, and the overall population. (Beydoun 2018)

Complete Blood Count (CBC)

White Blood Cell (WBC) Count

Elevated 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. (X. 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. (X. Wang 2025)

Neutrophil-Lymphocyte Ratio (NLR)

The NLR is a marker of systemic inflammation derived from standard 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)

Inflammatory Cytokines: Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Adiponectin

Elevated inflammatory cytokines, including TNFα, IL-1β, and IL-6, have been associated with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), reflecting both peripheral and central inflammation. Higher adiponectin levels, particularly in women, correlate with smaller hippocampal volume, poorer cognitive performance, and greater MCI risk. Together, these findings link chronic inflammatory signaling to neurodegeneration and cognitive decline. (Shen 2019)(Wennberg 2016)

Adiponectin

Oxidative Stress Markers 

Oxidative stress markers measure the balance between free radicals and antioxidants, which can influence neuronal health and cognitive longevity. Oxidative stress is significantly elevated in individuals with AD and MCI, highlighting its role in disease progression. (Schrag 2013)

F₂-Isoprostane

F₂-isoprostanes are stable indicators of oxidative stress, a process central to AD pathology. Elevated levels of F₂-isoprostane subtypes have been found in the urine, blood, and cerebrospinal fluid of AD patients, correlating with cognitive impairment and established AD biomarkers. (Praticò 2000) In a 14-year prospective study, higher urinary F₂-isoprostane levels were associated with increased risk of all-cause dementia and AD, particularly among apolipoprotein E epsilon 4 (APOE ε4) carriers. (Trares 2020)

For additional oxidative stress markers that may help in assessment, see the Cognitive Essentials for Healthy Aging clinical guide. 

Ingredients

Curcumin (from Curcuma longa)

Dosing: 800 mg once daily for at least 24 weeks (W. Wang 2025)

Supporting evidence:

• A 2025 systematic review and meta-analysis of nine randomized controlled trials (N=501) found that curcumin supplementation helps significantly improve global cognitive function due to its proposed antioxidant and anti-inflammatory neuroprotective mechanisms. The beneficial effects are dose- and time-dependent, with an optimal dose of 0.8 g/day and requiring a duration of at least 24 weeks. The effect was found to be more potent in older (60+ years) and Asian participants. (W. Wang 2025)
• An 18-month, randomized, double-blind, placebo-controlled (RDBPC) trial using 90 mg of curcumin found significant improvements in verbal memory, visual memory, and attention in older adults with memory complaints compared to the placebo. (Small 2018)
• A 12-month RDBPC study in community-dwelling older adults (n=96) using 1,500 mg/day of a highly bioavailable and standardized curcumin product found that the curcumin group did not experience the cognitive decline observed in the placebo group on the Montreal Cognitive Assessment (MoCA) at 6 months, although no significant differences were found between groups for all other cognitive measures. (Rainey-Smith 2016)

Saffron (Crocus sativus) Stigma Extract

Dosing: 15 mg twice daily for 4–12 months (Akhondzadeh 2010)(Farokhnia 2014)

Supporting evidence:

• In a 12-month single-blind trial in older adults with MCI, saffron supplementation helped improve memory and attention measures, suggesting potential benefits for cognitive longevity and neuroprotection. (Tsolaki 2016)
• In a 16-week randomized, placebo-controlled trial in patients with mild to moderate AD, saffron supplementation helped improve cognitive function compared to placebo, supporting its potential for maintaining long-term brain health. (Akhondzadeh 2010)
• A 12-month double-blind trial comparing saffron with memantine in patients with moderate to severe AD found that saffron demonstrated comparable efficacy in cognitive outcomes, with a favorable safety profile. (Farokhnia 2014)
• Saffron contains a range of bioactive phytochemicals, including alkaloids, anthocyanins, saponins, tannins, and flavonoids, which are associated with anti-inflammatory activity. (El Midaoui 2022)(Maqbool 2022) ​​Saffron can affect neurodegenerative disorders through cell signaling pathways, modulation of pro-inflammatory mediators, and inhibition of oxidative events. (Khazdair 2024)

Pentadecanoic Acid (C15:0)

Dosing: 100–200 mg once daily, for a minimum of three months (Robinson 2024)

Supporting evidence:

• Pentadecanoic acid (C15:0) is an odd-chain saturated fatty acid recently characterized as an essential nutrient with notable anti-inflammatory and antiproliferative activities. It also has the capacity to activate adenosine monophosphate-activated protein kinase (AMPK) and inhibit mammalian target of the rapamycin (mTOR)—mechanisms shared with established longevity-promoting compounds.  (Venn‐Watson 2022)(Venn-Watson 2023) These combined properties suggest that C15:0 could support neurological health, cognitive function, and memory by dampening neuroinflammation and enhancing energy-sensing pathways critical for neuronal resilience, synaptic maintenance, and long-term functional integrity. (Navakkode 2024) 
• Higher serum C15:0 levels are associated with better cognitive and memory scores, as demonstrated by the results of a cross-sectional study including 372 Chinese adults (mean age 58 years) with type 2 diabetes mellitus. Those with higher plasma C15:0 had higher Mini-Mental State Examination (MMSE), MMSE delayed recall, Montreal Cognitive Assessment (MoCA), and MoCA visual-spatial ability scores. (Shen 2022) 
• In one study, compared to healthy controls, patients with AD had lower free levels of C15:0 in the supernatant fluid fraction of cerebrospinal fluid, while nanoparticle-bound C15:0 was elevated. These findings imply that reduced availability of free C15:0 may contribute to compromised neuronal resilience, while accumulation in bound forms could represent a compensatory but maladaptive response that contributes to AD pathology. (Fonteh 2014)
• Safety studies at doses up to 250 mg have shown C15:0 is well-tolerated, with no significant adverse events reported. (Robinson 2024)