PH011 — Cognitive Clarity
Capacity to maintain clear, organised mental processing without excessive fog or confusion.
How clear and organised thinking feels — distinct from attention stability or raw mental energy.
Therapeutic areas: TA001 ★TA002TA003TA004TA005TA006TA007
Provenance: Core Version 1 registry phenome for mental processing clarity (distinct from Focus/Attention Stability PH001 and Cognitive Energy PH004). Enriched with cross-system oxidative and micronutrient biology. (origin: BRAIN)
Related phenomes: PH001 — Focus / Attention Stability, PH004 — Cognitive Energy Stability
External framework cross-references
RDoC domains
- Cognitive Systems — cognitive control / processing efficiency
DSM / ICD context
- Attention-deficit/hyperactivity disorder — cognitive symptoms
- Mild cognitive impairment
Foundational Evidence
Registry-level Phenome Evidence Confidence (below) is independent of Biology → Phenome Relationship Strength and Evidence Confidence on individual mechanism pages. Use the scoring guide for definitions of all three scores.
These are three independent scores. They are not combined or averaged. A phenome can have Medium registry evidence while individual mechanism rows show different relationship strength and evidence scores.
1. Phenome Evidence Confidence (Phenome Registry only)
Question: How convincing is the foundational evidence that this phenome is a valid, well-defined functional construct — and that diet-relevant biology can plausibly connect to it?
Not a roll-up of Biology → Phenome Relationship Strength or Evidence Confidence from Primary Mechanism page rows. Those are scored per mechanism; this score is assigned once per phenome at registry level.
Derived from foundational landmark evidence organised in up to three layers: construct validation, biology→phenome linkage, and nutrition→biology modulation. Each layer may include one or many landmark papers depending on registry review.
2. Biology → Phenome Relationship Strength (Primary Mechanism phenome rows)
Question: If this PM/FM biology were substantially impaired in isolation, how directly would that phenome be expected to suffer — within BRAIN architecture?
How it is derived: Reviewers read the PM/FM definition and biological function first — initially ignoring attached references and whether dietary intervention studies exist. References are reviewed only when scoring Evidence Confidence (below).
Score levels (the value shown on each row as Biology → Phenome Relationship Strength):
- High — primary biological determinant (e.g. noradrenergic signalling → attention; GABA synthesis → calming tone)
- Medium — major contributory determinant, not the sole driver
- Low–Medium — established but indirect, modulatory, or one integrative step removed
- Low — distal, conditional, or weak biological coupling
“Not dietary treatment efficacy” means this score does not ask whether a diet or supplement treats the phenome. It asks whether the biology itself is architecturally relevant. Limited dietary RCT evidence belongs in Evidence Confidence, not here.
3. Evidence Confidence (Primary Mechanism phenome rows)
Question: How convincing is the adjudicated evidence on that specific row that this biology actually relates to this phenome?
How it is derived: Assigned after Biology → Phenome Relationship Strength, by reviewing the relationship evidence on that PM/FM row. Judges whether the evidence supports the relationship — not just mechanism or phenome in isolation.
- High — strong convergent human evidence directly linking mechanism biology to phenome variation
- Medium — multiple human lines supporting the relationship; may include one bridge study with an inferential step
- Low–Medium — convergent translational stack without direct mechanism↔phenome measurement on the row
- Low — mechanistic or preclinical only; mechanism and phenome supported separately but not bridged
Often equal to or lower than Biology → Phenome Relationship Strength. Can occasionally be higher when outcome evidence is stronger than the mechanism's contributory role.
Phenome Evidence Confidence: Low–Medium
Oxidative-stress and omega-3 cognition reviews support biology→phenome; homocysteine and gut–estrogen links are mechanistic — clarity outcomes not isolated as primary endpoints on the stack.
Construct landmark papers
- Derbyshire & Maes (2023) — Neuroinflammation and oxidative stress in ADHD — cognitive symptom construct context.
- Liu et al. (2014) — Homocysteine and cognitive function — clarity/processing efficiency framing.
Biology → phenome landmark papers
- Verlaet et al. (2019) — Oxidative stress biology linked to ADHD cognitive symptom domains.
- Collaboration (1998) — Homocysteine lowering and cognitive outcomes — biology→clarity linkage.
Nutrition → biology landmark papers
- Oulhaj et al. (2016) — Omega-3 supplementation and cognitive performance — human nutrition→cognition support.
- Watson et al. (2019) — Gut–brain signalling and cognitive health — microbiome nutrition context.
Connected mechanisms
- BRS-X(ECS-PM2) — Omega-3-Derived Endocannabinoidome Signalling (modulates · Relationship Strength: Low · Evidence: Low)
BRS-X(Hormones)
- BRS-X(Hormones-PM1) — Oestrogen Signalling Stability (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS-X(Hormones-PM2) — Estrobolome Regulation (indirect · Relationship Strength: Low–Medium · Evidence: Low–Medium)
BRS1
- BRS1-FM2-PM6 — Acetylcholine Synthesis Support (modulates · Relationship Strength: Medium · Evidence: Low)
- BRS1-FM3-PM7 — Neuronal Membrane DHA Incorporation (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS1-FM4-PM10 — Glutamate Clearance & Recycling (modulates · Relationship Strength: Low · Evidence: Low)
BRS2
- BRS2-FM1-PM1 — Folate/B12-Dependent Homocysteine Remethylation (modulates · Relationship Strength: Low–Medium · Evidence: Low)
- BRS2-FM1-PM2 — Betaine/BHMT Remethylation (indirect · Relationship Strength: Low · Evidence: Low)
- BRS2-FM1-PM3 — SAMe Synthesis (modulates · Relationship Strength: Medium · Evidence: Low–Medium)
- BRS2-FM1-PM4 — Methionine Cycle Flux (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS2-FM3-PM7 — Phosphatidylcholine Formation (modulates · Relationship Strength: Medium · Evidence: Low–Medium)
BRS3
- BRS3-FM1-PM1 — NF-kB Signalling Regulation (modulates · Relationship Strength: Low–Medium · Evidence: Medium)
- BRS3-FM1-PM2 — Gut-Derived Inflammatory Signalling (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS3-FM2-PM3 — Nrf2-Mediated Cellular Defence Regulation (modulates · Relationship Strength: Low–Medium · Evidence: Medium)
- BRS3-FM2-PM4 — ROS Generation vs Clearance Balance (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS3-FM2-PM5 — Lipid Peroxidation Control (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS3-FM2-PM6 — Antioxidant Network Recycling (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
- BRS3-FM3-PM7 — Cytokine Network Modulation (modulates · Relationship Strength: Low · Evidence: Low–Medium)
- BRS3-FM3-PM8 — Eicosanoid / SPM Balance (modulates · Relationship Strength: Low–Medium · Evidence: Low–Medium)
BRS5
- BRS5-FM2-PM4 — Microbial Substrate-Processing Selection & Adaptation (indirect · Relationship Strength: Low · Evidence: Low)
- BRS5-FM2-PM6 — Polyphenol Biotransformation & Mitochondrial-Relevant Metabolite Generation (indirect · Relationship Strength: Low · Evidence: Low)