👤 Demographics
Age
70
Sex
10-yr baseline risk—
Irreducible floor—
Modifiable burden—
After interventions—
Irreducible
Modifiable
Protected
Controls
Risk (23)
Interventions (16)
A=Strong (RCT/large) · B=Moderate/observational · C=weaker · D=consensus. Lower grades excluded from the combined PAF.
Risk Decomposition (10-year cumulative probability) — Idiosyncratic floor is always > 0
—
Age/Sex Baseline
(population avg)
(population avg)
—
Irreducible Floor
(non-modifiable)
(non-modifiable)
—
Your Risk
(active factors)
(active factors)
—
After Interventions
(theoretical min)
(theoretical min)
Irreducible floor = Baseline × (1 − PAF_max = 0.527). Even with zero modifiable risk factors, this floor is never zero.
Baseline (Age/Sex)
—
—
Irreducible Floor
—
Baseline × 0.473; always > 0
Your Risk
—
—
After Interventions
—
Applying active protective interventions
Modifiable PAF
—
Fraction attributable to active risk factors
Protection RR
—
Combined HR of active interventions
Cases Prevented / 1,000
—
At your age/sex baseline
Active Risk / Interv.
—
of 23 risk / 16 interventions
Risk Decomposition — Stacked Components
Age-Sex Baseline Dementia Risk Curves
PAF by Active Risk Factor (sorted)
Hazard Ratio — All 23 Factors
Target Risk Reduction:
70%
= reduce personal risk from — to —
Sort order:
Set all adherence:
✓ Minimum Viable Protocol
—
Cumulative Risk Reduction (Pareto Order)
Individual Contribution by Intervention (Adherence-Adjusted)
Baseline is ALWAYS age-sex-adjusted (never zero):
Irreducible = Baseline(age,sex) × (1 − PAF_max) [PAF_max = 0.527 for all 23 factors]
Personal = Irreducible + Baseline × PAF_selected
do(X_i=0) = Personal − Baseline × PAF_i [Pearl interventional distribution]
Risk Factors
| Risk Factor | Stage | HR | Prev | PAF | Abs. Burden | Prevented/1k | do(X=0) Risk | E-Value |
|---|
Protective Interventions
| Intervention | Category | HR | Abs. RR (your baseline) | Saved/1k | Evidence |
|---|
PN = P(Y_{x=0}=0 | X=1, Y=1) — lower bound under monotonicity:
PN ≥ (HR − 1) / HR
PS uses YOUR age-sex baseline (not a generic 10%):
PS ≈ Baseline(age,sex) × (HR − 1)
| Factor | HR | PN (If-Not-For) | PS (Sufficient) | PNS | MR RR | RC Risk | HR−MR Gap |
|---|
PN (Probability of Necessity) by Factor
Observational HR vs Mendelian RR
E-Value (VanderWeele & Ding 2017) — minimum unmeasured confounding to nullify HR:
E-value = HR + √(HR × (HR − 1))
Both the confounder–exposure AND confounder–outcome association must be ≥ E-value simultaneously.
| Factor | Stage | HR | 95% CI | E-Val (HR) | E-Val (CI lower) | Robustness | RC Risk |
|---|
Causal DAG — Age & Sex as Root Nodes
Green=Early · Yellow=Mid · Orange=Late · Pink=Viral · Purple=Genetic/Root
DAG: Age and Sex are root nodes (purple) that directly modify baseline risk AND modulate multiple pathways (e.g., age → hearing loss, age → depression; sex → depression, sex → longevity). Pink = viral/infectious. Solid arrows = direct causal. Dashed = mediated. APOE ε4 amplifies herpes ×4.64 and impairs Aβ clearance.
🦠 Viral Hypothesis (Berkowitz/Moir/Itzhaki): Aβ is an innate immune antimicrobial peptide that envelops neurotropic herpesviruses. Aging immune senescence → clearance failure → microglial activation → tau → neuronal death.
Acyclovir 90d (Taiwan N=34M): HR 0.092; E-value 10.24 — strongest single protective signal in dementia prevention.
Antiviral HR by Drug & Duration (Taiwan NHIRD)
Acyclovir Dose-Response: Days vs Risk Reduction
Neurotropic Pathogens
| Pathogen | Prevalence | HR | E-Value | CNS Entry | Intervention | Evidence |
|---|
💊 Berkowitz Protocol — Zero Downside Risk Threshold. "Yokul-ten, dvun-weht, dif-tor heh smusma" — Eat less, move more, live long and prosper. All items pass zero-downside-risk screening.
Berkowitz Protocol — Causal Analysis
| Supplement / Intervention | Dose | HR / Effect | Mechanism | Evidence | Notes |
|---|
Mechanisms of Action — All 23 Risk Factors
| Factor | Stage | Primary Mechanism | Neuropathology | Intervention | Evidence |
|---|