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Curation log — vascular dementia

Newest entries first. Every content-changing session appends an entry: date, what changed, what was searched, follow-ups for next time. See CLAUDE.md.

2026-09-02 — Independent re-audit of Claude's second deepening pass (Codex auditor; Claude additions author)

Outcome. Re-audited the substantial additions recorded in the immediately preceding Claude-authored pass. All 19 wiki pages are now status: curated. The audit used fresh live PubMed E-utilities and ClinicalTrials.gov API responses in this session; no identifier was accepted from memory.

Citation and registry integrity

  • Extracted and live-resolved every wiki PMID. The pre-audit wiki contained 416 distinct PMIDs, all 416 of which resolved. After corrections it contains 417 distinct PMIDs: one unique orphan was removed and two live-resolved corrective records were added (PMID 36749936 and PMID 38583421).
  • Extracted and live-resolved every wiki NCT identifier. The final wiki contains 44 distinct NCT IDs. The 42 already present all resolved; the two corrective additions, NCT03863665 and NCT03785067, were then fetched individually from the live API and resolved to PROHIBIT-ICH and the TRIDENT Cognitive Sub-Study.
  • PubMed metadata comparison found no substantive title, author, journal or year mismatch among the 416 pre-audit records. Numerical spot-checks emphasized the high-risk passages named in Claude's handoff and supported their reported sample sizes and estimates; interpretive overreach was corrected separately below.
  • Four registry completion dates had changed and were refreshed from the live records: NCT07252544 to 2028-02, NCT07012629 to 2040-01, NCT04700826 to 2031-01, and NCT06933212 to 2027-07.

Claim-level corrections

  • Removed or softened unsupported causal, temporal, comparative and prescriptive language: GFAP “preceding” injury without baseline MRI; NfL change “outperforming” level; albumin quotient as a positive vascular-copathology indicator; observational DTI-ALPS ordering as proof; ASL heterogeneity as superior to mean perfusion; lenticulostriate pulsatility as proven upstream; cerebrovascular variance explained as a treatment-effect ceiling; cross-trial exercise-versus-drug equivalence; active-control causation; carotid haemodynamic causation; anticoagulation “failure”; CAA recurrence as a rule that should govern restart; and observational deprescribing findings as proof of benefit or safety.
  • Corrected the unsupported claim that no post-ICH prevention trial has a cognitive endpoint. The iDEF trial cohort has a published MoCA trajectory analysis (PMID 38583421), while PROHIBIT-ICH (NCT03863665) and the TRIDENT Cognitive Sub-Study (NCT03785067) include cognitive outcomes. The remaining gap is narrower: cognition is secondary or a substudy outcome rather than a primary clinical dementia-prevention endpoint.
  • Corrected the burden narrative after a targeted search found contemporary VaD-specific US Medicare costs (PMID 36749936). The older Swedish study remains the located VaD-specific societal estimate; the modern record measures direct payer cost and does not close that societal-cost gap.
  • Reframed qualitative caregiver, successful-reperfusion, financial-capacity and cross-country cost findings to match their designs and avoid unsupported generalization.

Absence searches rerun

  • Exercise versus cholinesterase inhibitor: targeted PubMed search returned reviews/management literature but no head-to-head randomized trial; claim retained with cross-trial-comparison caveat.
  • Fabry randomized cognitive endpoint: targeted PubMed search returned no qualifying randomized cognitive-endpoint trial; claim retained.
  • Contemporary VaD-specific societal cost: targeted search found the 2023 Medicare subtype study (PMID 36749936), which is direct health-care cost, but no contemporary societal total; wording narrowed accordingly.
  • Validated sporadic-SVD patient-reported outcome: targeted PubMed search found the CADASIL-specific CADA-PRO validation (PMID 39234671) but no validated sporadic-SVD-specific instrument; claim retained and scoped.
  • Post-ICH cognitive-endpoint trial: claim failed, was removed, and was replaced with the live evidence above.

Padding and breadth

  • Removed five orphan reference entries from overview.md, one from mixed-pathology-and-alzheimer-overlap.md, and one from monogenic-and-inherited-forms.md. Six of those PMIDs remain legitimately body-cited elsewhere in the wiki; PMID 20851424 was the one unique record removed.
  • The condition's distinct-records-per-page figure was 416 / 19 = 21.89 before this audit and is 417 / 19 = 21.95 after it. The Claude deepening therefore survives the breadth check: the audit removed padding while adding only evidence needed to correct two incomplete or false claims.
  • Final wiki size: 4,006 lines across 19 pages. No unresolved claim or identifier defect remains from the audited additions.

2026-09-02 — Second deepening pass: widening the evidence base (Claude author; independent re-audit pending)

Why this pass ran. After the first deepening pass the condition was structurally complete and page-level citation density looked adequate, but the measure that matters was low: 17.6 distinct PubMed records per page across the whole condition (335 distinct PMIDs / 19 pages), against 15.4–21.1 for the reference conditions. A condition can look well cited page by page while every page recycles one shared pool. The brief for this pass was therefore to widen the source base — bring in records the condition did not yet cite, sourced to each page's own topic — not to lengthen pages with the references they already had.

Result. 335 → 416 distinct PMIDs across the wiki (21.9 distinct records per page), with 3,578 → 4,011 lines. Every one of the 416 was re-resolved through live PubMed E-utilities on 2026-09-02; all 416 resolved. All 19 pages set to status: draft for independent re-audit.

What was deepened, page by page

Page Records added What they added
nosology-and-diagnostic-criteria.md 5 Knopman's population-based validation (sensitivity 0.75 vs the hospital-series 0.20–0.25 — a criteria-architecture rather than criteria-quality difference); Cerullo's pooled κ 0.79 for ICD-10 VaD against Chui's 0.30–0.61; Erkinjuntti's subcortical-VaD research criteria as the abandoned homogeneity strategy; Hsiung's 40% two-year VCI-ND conversion and 14% reversion
epidemiology-and-burden.md 5 Hisayama incidence (9.5/1,000 py, six times Rotterdam/NEDICES despite stronger ascertainment); the internally inconsistent Chinese prevalence set (VCI 1.54% ≤ VaD 1.6%); Cao's male-predominant VaD prevalence against EURODEM's sex-neutral incidence; the only VaD-specific societal cost estimate (23% above AD)
cerebral-small-vessel-disease.md 6 the three-way perivascular-space contradiction (count vs volume vs DTI-ALPS); Framingham's multimarker score (HR 1.76, c 0.82–0.83, indistinguishable from a risk questionnaire); microinfarct prevalence by pathology (62% of VaD brains); LADIS cognitive reserve; Persyn's 31-locus GWAS
cerebral-amyloid-angiopathy.md 6 Case's quantified MCI prevalence (79%) and vascular cognitive profile; Pfeifer's CAA × AD interaction (45.9% vs 16.6% CASI deficit) against Sin's null mediation; Charidimou 2013 and Roongpiboonsopit's siderosis recurrence curves (74% at 4 years disseminated; 7% at 6 months); a new section on iatrogenic CAA — the only transmissible substrate in this condition
monogenic-and-inherited-forms.md 6 Rutten's 12-year onset gap by EGFr position, which is the mechanism generating the 40-fold prevalence gap; Liem's 7-year longitudinal finding that WMH change is unrelated to cognitive decline in CADASIL; Brice's post-50 non-linear trajectory; a direct HTRA1-vs-NOTCH3 imaging comparison; the COL4A1/2 epilepsy phenotype; the nearest randomized Fabry ERT evidence
pathophysiology.md 5 Kisler's capillary-level pericyte mechanism and Miners' human tissue dissociation of pericyte loss from barrier leakage; Montagne's age-dependent hippocampal BBB breakdown; Claassen's four-system decomposition of "cerebral autoregulation"; Santisteban's venous and lymphatic neurovascular ageing
mixed-pathology-and-alzheimer-overlap.md 5 Boyle 2013/2021 — eleven pathologies explain 43% of decline variance and the cerebrovascular block explains 3–8%; a Chinese community brain bank where LATE-NC exceeds ADNC; Jellinger's 1,700-autopsy age gradient; Barnes's sex-patterned AD+CVD
subtypes-and-clinical-syndromes.md 4 strategic lacunes in a population sample (brainstem for non-amnestic MCI); tract-specific strategic WMH outperforming total WMH volume; CREST-2's memory-predominant non-lateralized deficit against the haemodynamic account; Swiss-AF's 85%-silent infarcts under anticoagulation
cognitive-profile-and-assessment.md 4 Shi's MoCA cut-point analysis (optimum 20/19); the Cochrane IQCODE threshold problem; Demeyere's OCS-vs-MoCA head-to-head exposing MoCA's left-hemisphere bias; a BPSD-by-subtype table (apathy 62% in subcortical VCI, hallucinations 26.6% in mixed)
neuroimaging.md 4 Kapeller's collapse of visual-rating agreement for progression (κ 0.19–0.39) against baseline (0.59–0.78); Wahlund's MTA rating beating its own volumetry; ASL spatial coefficient of variation outperforming mean perfusion; 7T lenticulostriate pulsatility present independently of visible SVD and absent in the MCA
biomarkers.md 5 Qu's NfL rate-of-change signal and Prapiadou's finding that GFAP predicts SVD markers nine years ahead while NfL does not; Skillbäck's 1,861-patient albumin-quotient series; the counterintuitive direction of CSF MMP-2; OCT-angiography against sub-visible white-matter damage
post-stroke-cognitive-impairment.md 4 Pendlebury's dissociation of delirium (independent of white-matter disease) from infection (conditional on it); Fang's 15.5% covert incident lesions at 6 months; the post-ICH trajectory (32–37% at 5 years) and Taiwan's subtype hazard ordering
prevention-and-risk-factor-control.md 5 He 2025 — the first adequately powered randomized trial with dementia as its primary outcome to be positive (RR 0.85 on a 22 mm Hg contrast in 33,995 adults); HYVET-COG; Gottesman's midlife diabetes hazard approaching APOE ε4; Smith's age-window attributable fractions (2–8% after 80); Chinese PAF composition
treatment.md 5 Black 2003 and the 54-week open-label extension; a new section on exercise, whose ADAS-Cog effect (−1.71) exceeds donepezil 5 mg; citicoline's post-stroke attention-executive signal
guidelines.md 4 EAN 2020 (vascular risk as management, anticoagulation without imaging conditioning); the retired AAN MCI guideline that grades exercise above drugs; ACR imaging appropriateness; Alzheimer's Association DETeCD-ADRD
clinical-trials-landscape.md 0 new PMIDs, 9 new NCTs a fresh ClinicalTrials.gov v2 sweep that found the phase-3 successor to LACI-2 the 2026-08-31 sweep recorded as absent (IMPACT, NCT07252544, n=3,156), plus a cilostazol phase-4, a CADASIL BBB-endpoint phase-2, and a covert-brain-infarct phase-3
red-flags-and-safety-concerns.md 4 the anticholinergic prognostic-versus-intervention asymmetry (102,684 vs 299 participants); randomized antihypertensive deprescribing (no harm, and no fall reduction); financial capacity and exploitation
patient-experience-and-advocacy.md 4 the caregiver-burden reversal by disease severity; the invisibility problem created by successful reperfusion; Argentine cost data replicating the US hospital-heavy profile
overview.md 8 new to the condition (13 reference entries; five were already cited on other pages) controversies table expanded from 8 to 13 rows; prevention/treatment table extended with the 2025 BP trial, exercise, and the lipid null

Literature layer

  • BIBLIOGRAPHY.md: found and closed a pre-existing gap — 118 records were cited in wiki pages but absent from the bibliography — and added the 81 records introduced by this pass. 199 entries added; wiki-to-bibliography coverage is now complete (0 cited-but-unlisted). Entries are grouped by first-citing page in the house format with full cited by lists.
  • STATISTICS.md: 23 → 34 sections, adding country-specific VaD prevalence/incidence, cost of vascular dementia, population attributable fractions by age window, randomized blood-pressure prevention with achieved contrasts, exercise and non-drug intervention, BPSD by subtype, additional criteria performance, additional SVD markers, imaging measurement reliability, post-stroke covert injury and delirium, mechanism/biomarker quantities, and neuropathology variance explained. Twelve new rows in "known conflicts and caveats", including the internally inconsistent Chinese prevalence set and the Hisayama incidence gap.
  • REGISTRY.md: 21 → 25 records (EAN 2020, AAN 2018 retired, ACR 2024 update, Alzheimer's Association DETeCD-ADRD 2025), with per-record notes, five new disagreement rows (exercise-versus-drugs; anticoagulation conditioning; guidelines not yet reflecting the 2025 BP trial; who owns imaging selection; primary-care pathways), and five watch-list additions.
  • OPEN-QUESTIONS.md: OQ-2 sharpened and partly closed by the 2025 BP trial; six new questions (OQ-31 to OQ-36) on exercise-versus-drug head-to-head, anticholinergic deprescribing, which PVS measurement carries information, the Hisayama incidence gap, GFAP as the earliest signal, and whether haemorrhagic and non-haemorrhagic CAA are one disease; ten new junctions (D18–D27); four questions moved to the closed/downgraded table.

Searches run

Roughly 90 PubMed E-utilities queries across every page's topic (criteria validation and reliability; secular trends and country-specific epidemiology; cost; SVD burden scores, perivascular spaces, microinfarcts, GWAS; CAA prevalence, siderosis recurrence, inflammation, iatrogenic transmission; CADASIL natural history and genotype-phenotype, HTRA1, COL4A1/2, Fabry; neurovascular coupling, BBB permeability, pericytes, autoregulation, glymphatics; mixed pathology, LATE-NC, hippocampal sclerosis, non-Western autopsy cohorts; strategic lesions, carotid stenosis, heart failure, atrial fibrillation; MoCA/MMSE/OCS/IQCODE accuracy, apathy and BPSD; visual rating reliability, MTA, ASL, 7T perforators, FDG-PET; plasma NfL/GFAP, albumin quotient, MMPs, retinal imaging; post-stroke trajectories, delirium, ICH, thrombectomy; HYVET, SCOPE, ARIC, Chinese BP trials, smoking, physical activity, attributable fractions; memantine, nimodipine, cilostazol, citicoline, donepezil, exercise; guideline bodies), plus three live ClinicalTrials.gov v2 condition queries and eight single-study API fetches.

What was deliberately left alone

  • literature/notes/ — the five landmark notes were not touched. None of this pass's additions is a practice-changing landmark of the kind the notes are reserved for, with the possible exception of He 2025 (the positive cluster-randomized BP trial); a note for it is a reasonable follow-up but it is one trial, open-label, and not yet replicated or subtype-adjudicated.
  • literature/patient-voice/ — the four files were not touched. Organization URLs still need re-fetching at the next audit; this pass added no non-journal sources.
  • Page structure — no page was restarted, no verified content deleted, no section removed. Every edit is an insertion or an extension of an existing sentence, except where an explicitly stale claim needed correcting (see below).
  • Five orphan references in overview.md (PMIDs 20660506, 31248555, 31294622, 37222252, 8094895) and one each in mixed-pathology-and-alzheimer-overlap.md (31248555) and monogenic-and-inherited-forms.md (20851424) sit in reference lists without a body citation. These predate this pass; they were left in place rather than deleted, since removing pre-existing content is outside this pass's brief. They are flagged here for the auditor.

Corrections made to existing content

  • clinical-trials-landscape.md carried a dated absence claim — that no registered phase-3 successor to LACI-2 existed. A repeat registry query two days later found IMPACT (NCT07252544). The claim was corrected in place and re-labelled as a query-coverage artifact, and the general lesson (registry absence claims decay within days) was added to the statistics conflicts table.
  • prevention-and-risk-factor-control.md and overview.md framed "does blood-pressure lowering prevent dementia?" as an open two-sided controversy. That framing is no longer accurate for all-cause dementia at large achieved contrasts and was rewritten around He 2025, with the residual open components (target, treated populations, subtype adjudication) stated explicitly.
  • monogenic-and-inherited-forms.md carried a dated evidence-gap sentence about Fabry enzyme replacement. It was replaced with the nearest randomized evidence (Fellgiebel 2014, white-matter lesion stability in a phase-4 subgroup, NNT 8) plus a re-dated absence statement for cognitive endpoints.
  • Reference lists were renumbered on every edited page, and one missing reference entry was added to clinical-trials-landscape.md. Every page now has zero body-cited-but-unreferenced PMIDs.

Follow-up for the independent auditor

  1. Re-fetch all 416 wiki PMIDs and the 9 new NCT records; check each new numeric claim against its abstract, particularly the effect sizes in the He 2025, Liu-Ambrose, Paradise/Hong/Hilal, Boyle, and Pfeifer passages.
  2. Re-run the searches behind the absence claims this pass makes or preserves: no head-to-head exercise-versus-cholinesterase trial; no randomized cognitive-endpoint trial in Fabry disease; no contemporary VaD-specific societal cost estimate; no validated patient-reported outcome for sporadic SVD; no post-ICH trial with a cognitive endpoint. Stale absences are the most common real error.
  3. Decide whether the five orphan overview references should be removed or given body citations.
  4. Consider whether He 2025 warrants a literature/notes/ entry.
  5. Re-fetch the patient-voice organization URLs, which have not been checked since the build.

Could not verify in this pass: the vascular-dementia-specific effect of the 2025 cluster-randomized blood-pressure trial (it reported all-cause dementia only); whether the Hisayama-versus-European incidence gap has ever been formally decomposed (no such analysis was found); contemporary societal cost of vascular dementia outside the 2003 Swedish and 2011 Argentine estimates.

2026-08-31 — Independent audit of the deepening pass (Grok auditor; Claude author)

Audited the new material Claude added to all 19 wiki pages (previously curated content was not re-litigated except where a new claim attached to it). Did not treat the deepening pass as trustworthy. Re-fetched 217 wiki PMIDs via PubMed E-utilities esummary (all 217 resolved) plus 66 priority abstracts and targeted MEDLINE XML for numeric claims. Re-fetched 25 NCT IDs via ClinicalTrials.gov v2 (all resolved; statuses and enrollments match the trials table). Re-ran absence searches for confirmatory Cerebrolysin/Actovegin trials, LACI-3, VASCOG/VICCCS/VasCog-2-WSO autopsy validation, Fabry ERT cognitive prevention, and VaD-specific behavioral RCTs.

Claim–citation pairs checked. Principal new tables and quantitative paragraphs on treatment, nosology, guidelines, prevention, epidemiology, SVD, biomarkers, CAA, mixed pathology, trials, PSCI, monogenic disease, neuroimaging, cognitive assessment, subtypes, red flags, and patient experience. Landmark numbers that matched their abstracts include: Orgogozo/Wilcock memantine; Cheng 2026 16 trials/5,668 and memantine MD −2.20; Shi 2022 SMD −1.11/−1.99 and CDR-SB/EXIT25; Dang 194 RCTs/21 drugs; Guekht Cerebrolysin −6.17 and 67.5% vs 27.0%; ARTEMIDA −2.3; Jia NBP −2.46/−1.39 and 57.1% vs 42.1%; Kwan NBP MD −1.07 (Jia included as putative antiplatelet); Wieland SKT −1.86 and ADL −0.19 with I² 96%/91%; CONIVaD 15% nimodipine adherence; LACI-2 6-month Bath 2026; COMCID −1.8 vs −1.3 at 50 mg bid; OxHARP pulsatility/CVR/perfusion; Gold 1997/2002 and Bacchetta 42%; Chui κ 0.30–0.61; Syst-Eur 50%/55%; Charisis d −0.40; US POINTER 0.029 SD/y; LatAm-FINGERS 0.11 SD/y; Reddin OR 0.96; Guo HR 0.74/0.58; Ott/NEDICES/EURODEM/Honolulu incidence; Liang HR 5.90/1.33 and VaD −1.27 y; Mobley HR 1.68; Boyle 94%/22–100%; Lamar 80%/37%/63%; Yu 1,633/280/five profiles; RUN DMC HR 1.76; Sargurupremraj OR 1.43 vs HR 1.02; Cho 1 in 277; Hack OR 10.81; CROMIS-2 9.8 vs 2.6 per 1,000 py and HAS-BLED C=0.41; SoSTART/COCROACH; CAA recurrence 23%; PRESTIGE-AF siderosis HR 7.7; Edinburgh 12/16/26%; Rabin n=1,722; LAAO 5.16/2.73; MarkVCID PSMD/free-water/CVR/WMH ICC; Kim Dice 0.659/0.722 vs human 0.744; Lo STROKOG trajectories; Kusec C=0.76; Andrew 84%.

Confirmed author decisions. Wieland's dementia global-clinical-status estimate (MD −0.06, 95% CI −1.00 to −0.20) has the point estimate outside its interval; it remains omitted, now with an explicit note. Li 2025's Ginkgo MoCA interval (MD 1.29, 1.24–1.35) is implausibly narrow and was correctly not quoted.

Errors found and fixed - Ding 2026 (PMID 41962914) and Cunningham 2021 (PMID 34028812) both report dementia OR 0.89 but are not the same four-trial set: Ding includes PROGRESS (prior stroke/TIA; 16,823 participants: Syst-Eur, PROGRESS, SCOPE, HYVET-COG); Cunningham is restricted to people without prior cerebrovascular disease (236/7,767 vs 259/7,660). Corrected on the prevention page and STATISTICS.md. - Zhang 2026 IRVR PACC contrast (PMID 41870419): the published abstract prints "0.1 units; 95% CI −0.3 to 0.03", which places the point estimate outside the interval. Arm means (+0.2 IRVR vs +0.3 no-IRVR) imply −0.1. Corrected on the prevention page and STATISTICS.md. - Cerebrolysin Cochrane (PMID 31710397): 6 trials/597 were eligible, but SMD 0.36 is 3 trials/420 and RR 2.69 is 2 trials/379. The deepening pass attributed both estimates to the 6/597 set. Corrected on treatment.md and OPEN-QUESTIONS.md. - Stale absence: a VaD-specific BPSD RCT exists (Pessoa 2026, PMID 41277041; n=30, CBD 300 mg/day × 4 weeks, NPI/BPRS reduced, no cognitive/functional change). Added to treatment.md and BIBLIOGRAPHY.md. The "no VaD-specific behavioral RCT" sentence is retired. - Kwan 2022 (PMID 35833913) numbers for NBP were correct but the framing "Cochrane re-analysis" omitted that NBP entered an antithrombotic-therapy review as a putative antiplatelet. Clarified.

Padding removed. Unused reference-list entries (no body citation) deleted and said so: Markus 2022 on treatment.md; O'Brien and Battle on cognitive-profile-and-assessment.md; Hankey 2013 on post-stroke-cognitive-impairment.md; duplicate Bhanu 2021 on red-flags-and-safety-concerns.md; duplicate Wardlaw plus unused McShane on guidelines.md; Liu 2023, Debette 2010, and Wardlaw 2019 on neuroimaging.md; O'Brien and Gorelick on patient-experience-and-advocacy.md; Pearce, Wardlaw 2019, and Greenberg 2020 on subtypes-and-clinical-syndromes.md; Pantoni and Kalaria on pathophysiology.md; Wardlaw 2013, Iadecola 2019, and Greenberg 2020 on biomarkers.md.

Absence searches re-run (2026-08-31). No VASCOG/VICCCS/VasCog-2-WSO autopsy validation (0 hits). No confirmatory Actovegin trial. Cerebrolysin 2020–2026 hits were a review and an introduction, not a new eligible RCT. No LACI-3 on ClinicalTrials.gov (only LACI-1 NCT02481323 and LACI-2 NCT03451591). No Fabry ERT randomized cognitive-prevention trial. Covert-SVD antiplatelet "do not recommend" remains supported.

ClinicalTrials.gov. All 25 tabulated NCT IDs resolved. FINGER (NCT01041989) and ASPREE (NCT01038583) remain registry-status "unknown" despite published results. No registered phase-3 LACI-2 successor. The ISRCTN coverage limit stands.

Promotion. All 19 wiki pages set to status: curated after the corrections above. INDEX.md updated.

Remaining limits (not unmarked errors). Regulator labels were not independently retrieved. Li 2025's Ginkgo MoCA interval is still not quoted. The Korean NOTCH3 genetic prevalence (1 in 277) is ancestry-specific and already so labelled. Several pages remain in the 136–200 line range with 15–38 unique PMIDs.

Searches run. PubMed E-utilities esummary on 217 wiki PMIDs; efetch abstracts for 66+ priority records and XML for Saito, Cui, Yu, Lamar, Rodrigues, Rabin, Kim, Ding, Zhang, Pessoa; esearch for butylphthalide Cochrane, VASCOG autopsy validation, Cerebrolysin 2020–2026, Actovegin confirmatory, LACI-3, Fabry ERT cognition, VaD behavioral RCTs. ClinicalTrials.gov v2 for 25 NCT IDs plus condition queries (vascular cognitive impairment; cerebral small vessel disease; LACI-3).

Follow-up. Next sweep should watch for a published correction of Zhang 2026's IRVR interval, any independent replication of Pessoa 2026, LACI-3 if it appears on ISRCTN, and any vascular-dementia-specific drug-label change (retrieve the label, not a review).

2026-08-31 — Deepening pass (Claude)

What this pass was. Not a sweep and not a rebuild. The condition was structurally complete but thin at 125 lines and ~15 distinct citations per page, against reference conditions running 155–177 lines and 21–37 citations. This pass went page by page through all 19 wiki pages, ran substantially more literature searches than the build did, and extended pages with what was missing: landmark trials with actual effect sizes and intervals, competing guideline positions with their grades, quantified epidemiology in place of qualitative statements, deeper mechanism, and explicit controversies cited on both sides. Nothing verified was deleted and no page was rewritten from scratch.

Result. 19/19 pages extended; total wiki lines 2,376 → 3,009 (mean 125 → 158); distinct PMIDs per page mean ~15 → ~22; distinct verified PMIDs across the condition 121 → 218.

Page Lines (before → after) PMIDs (before → after) Principal additions
treatment.md 133 → 200 21 → 38 MMM 300/MMM500 memantine trials with numbers; the raw-scale-vs-SMD measurement dispute (Cochrane vs Shi 2022); the Western-null vs Asia-positive split (194-RCT Bayesian NMA); a table of agents with one positive pivotal trial and no confirmation (Cerebrolysin, Actovegin/ARTEMIDA, butylphthalide, EGb 761); CONIVaD adherence finding; cilostazol stroke-benefit vs null COMCID; LACI-2 6-month results; OxHARP
prevention-and-risk-factor-control.md 116 → 153 20 → 31 Syst-Eur as the field's outlier with three competing explanations; Cochrane and drug-class NMA against it; SPRINT global-SVD-factor dose-response; AF rhythm-control/ablation observational signal; definitive lipid-lowering null; a FINGER-replication table (US POINTER, LatAm-FINGERS, the null 2×2 exercise/IRVR trial) with the active-control problem; ACHIEVE
epidemiology-and-burden.md 154 → 189 13 → 21 Community incidence table (Rotterdam, NEDICES, EURODEM, Honolulu-Asia); the sex-neutrality of vascular-dementia incidence; mortality and survival meta-analysis; global informal-care cost; secular-trend systematic review; the AF/low-conventional-risk vascular-dementia excess
nosology-and-diagnostic-criteria.md 153 → 192 20 → 24 Full autopsy-validation table for ADDTC/NINDS–AIREN/DSM-IV/ICD-10/HIS, interrater κ, the 0.20–0.25 sensitivity of the "probable" tiers, mixed-dementia misclassification rates, and the 42%-no-stroke finding in the oldest old
cerebral-small-vessel-disease.md 127 → 156 20 → 28 RUN DMC 14-year progression-to-dementia data; the two-sample-vs-individual-level Mendelian randomization contradiction; two independent drug-target MR analyses nominating calcium-channel blockade; the null perivascular-space/cognition result; disappearing acute cortical microinfarcts; MINERVA
biomarkers.md 122 → 160 11 → 19 MarkVCID staged-qualification section with all four validated kits and their numbers; the plasma NfL/p-tau217/GFAP dissociation between vascular and Alzheimer pathology
clinical-trials-landscape.md 120 → 185 13 → 28 Live 2026-08-31 ClinicalTrials.gov sweep adding eight studies with a coverage-limit note; a "what the failures taught" table across six trials; an endpoint-readiness table grading six candidate markers
overview.md 139 → 177 30 → 49 Eight-row index of live controversies with citations on both sides and page pointers; community incidence and survival anchors
mixed-pathology-and-alzheimer-overlap.md 124 → 150 13 → 17 Boyle person-specific attributable fractions (22–100%); Lamar's finding that single cerebrovascular pathologies do not accelerate decline; Yu's five empirical neuropathologic profiles
monogenic-and-inherited-forms.md 119 → 152 12 → 16 Clinical-vs-genetic CADASIL prevalence (~40-fold gap); the three-tiered NOTCH3 EGFr risk classification superseding the 1–6/7–34 dichotomy; aggregation-not-signalling mechanism
red-flags-and-safety-concerns.md 127 → 149 16 → 20 CROMIS-2 absolute ICH rates and the HAS-BLED C-index of 0.41; basal-ganglia perivascular spaces as an ICH marker; SoSTART and the COCROACH IPD meta-analysis
cerebral-amyloid-angiopathy.md 123 → 148 16 → 21 23% recurrence with its predictors; PRESTIGE-AF imaging subanalysis (siderosis stratifies, "probable CAA" does not); Edinburgh CT criteria for MRI-poor settings; the CAA→plaque→tau mediation result; LAAO evidence
post-stroke-cognitive-impairment.md 123 → 150 12 → 17 STROKOG trajectory classes and long-term decline rates; the executive-function exemption; failure of general-population risk models (CAIDE AUC 0.53) and the stroke-specific replacement
guidelines.md 117 → 152 14 → 18 Four-column comparison of ESO–EAN, ESO covert-SVD, Korean CPG, and the Asian EGb 761 consensus with each body's stated position per question; the two irreconcilable disagreements named explicitly
pathophysiology.md 121 → 138 15 → 19 Periventricular-vs-deep WMH mechanistic split and the perilesional penumbra; 7 T CADASIL evidence that vascular dysfunction is locally causal and globally uninformative; OPC-recruitment failure as the rate-limiting repair step
neuroimaging.md 117 → 141 12 → 15 Automated WMH segmentation benchmarked against human inter-rater reliability on 8,421 patients, with the volume-vs-voxel distinction and the uncertainty index; ML systematic review's performance-vs-rigour gap
cognitive-profile-and-assessment.md 118 → 140 11 → 15 Direction-specific cutoff non-transportability (MoCA lower in less-WEIRD populations); Oxford Cognitive Screen development and independent psychometric critique; the OCS-based prediction model
subtypes-and-clinical-syndromes.md 111 → 141 19 → 25 Multivariate lesion-symptom mapping for "strategic" infarcts with its language-testing caveat; asymptomatic carotid stenosis as the cleanest hypoperfusion test; the pathology finding that single substrates may not count; CAA recurrence anchor
patient-experience-and-advocacy.md 112 → 136 12 → 16 Quantified unmet need (84%, peaking in year two); the clinician-described VCI "no-man's land"; psychoeducation evidence concentrated on aphasia; CADA-PRO and the absence of a validated sporadic-SVD patient-reported outcome

Searches run. Roughly 60 PubMed E-utilities searches across pharmacotherapy (memantine, Cerebrolysin, actovegin, nimodipine, cilostazol, ginkgo, butylphthalide, network meta-analyses), prevention (Syst-Eur, HYVET, Cochrane antihypertensives, multidomain trials, statins, AF rhythm control, hearing, CPAP), epidemiology (population incidence cohorts, secular trends, mortality, cost), criteria validation, SVD mechanism and genetics, biomarker qualification, imaging automation, CAA recurrence and anticoagulation trials, monogenic prevalence and genotype-phenotype, screening accuracy, and patient experience. Two live ClinicalTrials.gov v2 condition queries (vascular cognitive impairment; cerebral small vessel disease; lacunar stroke) plus eight single-study record fetches.

Literature layer. BIBLIOGRAPHY.md 138 → 294 lines: 110 records added in 13 new topic groups, each with tags and cited-by pages; all 110 were re-resolved through live efetch before writing. STATISTICS.md 108 → 356 lines: fourteen new quick-reference sections (9 → 23 total) (community incidence; mortality and cost; post-stroke trajectory and prediction; criteria-versus-autopsy accuracy; large-series neuropathologic composition; SVD markers and progression; biomarker validation; haemorrhage risk and anticoagulation; expanded prevention and drug trials; imaging automation; monogenic frequency; screening across populations; patient-reported burden), and nine new rows in the known-conflicts table. guidelines/REGISTRY.md 78 → 103 lines: three guideline records added (ESO–EAN 2021, Asian EGb 761 consensus 2019, Korean Dementia Association 2025), with per-record notes and six new disagreement rows naming the contradictions explicitly.

OPEN-QUESTIONS.md 122 → 206 lines: five existing Tier 1 questions (OQ-1, OQ-2, OQ-5, OQ-6, OQ-7) sharpened with the new evidence; five Tier 1 questions added (OQ-21 Asia-Pacific pharmacology, OQ-22 unconfirmed pivotal trials, OQ-23 surrogate mediation, OQ-24 raw-vs-standardized effect framing, OQ-25 single-vs-mixed cerebrovascular pathology); five Tier 2 added (OQ-26 to OQ-30); a new table recording six questions the pass closed or downgraded; and seven new junctions D11–D17.

Verification. Every PMID and NCT written in this pass came from a live PubMed E-utilities or ClinicalTrials.gov v2 query in this session. After writing, all 218 distinct PMIDs appearing anywhere in the condition were re-fetched in a single sweep and all 218 resolved. All 19 wiki pages were set to status: draft for re-audit. Internal link check: 0 broken relative links across wiki pages, INDEX, OPEN-QUESTIONS, and the literature layer.

What I deliberately left alone.

  • literature/patient-voice/ (README, organizations, themes, sources) — organization entries require live site fetches with recorded access dates and carry the ethics rules in CONVENTIONS §3. This pass was a literature deepening, not a patient-voice re-verification, and stale organization URLs should be re-fetched rather than inherited.
  • literature/notes/ — the five landmark notes are correct and their papers remain landmarks. Several 2024–2026 papers surfaced in this pass are strong candidates for new notes (Boyle 2018 PMID 29244218 for person-specific attribution; Jacob 2023 PMID 37073486 for SVD progression causality; Lo 2022 PMID 34775838 for the post-stroke decline curve; the COCROACH IPD meta-analysis PMID 37839434), but writing them is a separate task.
  • The Alzheimer's-disease border. No Alzheimer-side content was added beyond what the overlap and CAA pages need; amyloid/tau staging and anti-amyloid therapy remain owned by conditions/alzheimers-disease/.
  • INDEX.md page list — unchanged; the canonical 19-page structure was adequate and the brief was to add substance, not structure.
  • Pages I judged closest to complete at their current length: cerebral-amyloid-angiopathy.md and subtypes-and-clinical-syndromes.md were already dense for their scope, and received targeted additions (recurrence quantification; lesion mapping and the single-substrate pathology finding) rather than proportional expansion.
  • Three sourced-but-unresolvable gaps were left as stated gaps rather than filled: regulator label histories for vascular-dementia drugs (not retrievable from PubMed); ISRCTN-registered trials, which the ClinicalTrials.gov sweep cannot see and which the LACI-2 registration shows is a real coverage limit — this is now stated in the trials page rather than left implicit; and prospective validation of VASCOG/VICCCS/VasCog-2-WSO against autopsy, which does not exist and is recorded as OQ-1's sharpened form.

Follow-up for the auditor. (1) Re-fetch every PMID and check claim-to-record alignment, with particular attention to the numbers in the new comparison tables in treatment.md, nosology-and-diagnostic-criteria.md, guidelines.md, and STATISTICS.md. (2) Two published abstracts contain internally inconsistent figures that I handled by omission rather than correction — the Cochrane ginkgo dementia global-clinical-status estimate (point estimate outside its stated interval, PMID 41641880) and the Li 2025 Ginkgo MoCA interval, which is implausibly narrow (PMID 41404461); the latter is cited with an explicit caveat, the former is not cited. Confirm both decisions against the full texts. (3) Verify the ClinicalTrials.gov table by re-querying, since registry status changes. (4) Consider promoting pages to curated only after the numeric spot-checks pass.

2026-08-31 — Independent audit (Grok auditor; Codex author)

Audited all 19 wiki pages and the literature layer. Did not treat the Codex build as trustworthy. Re-fetched 80 original PMIDs (all resolved) plus 41 additional PMIDs added during audit (121 distinct PMIDs in the condition after expansion). Re-fetched 12 original NCT IDs (all resolved) plus 5 landmark NCT IDs (SPS3 NCT00059306, SPRINT NCT01206062, FINGER NCT01041989, ASPREE NCT01038583, LACI-2 NCT03451591). Checked claim–citation pairs on every page for existence, author/year/journal match, direction, and quoted numbers.

Claim-citation pairs checked: every inline PMID/NCT on the 19 wiki pages, OPEN-QUESTIONS, bibliography, notes, guideline registry, statistics, and patient-voice files (well over 200 pairs). Numeric claims that matched their abstracts include Schneider 38.0/30.0/12% and OR 2.8; Pendlebury 14.4/9.1/7.4/41.3%/3.0% per year and 93% variance; Barbay 53.4/36.4/16.5%; Hughes OR 0.93 and ARR 0.39%; SPRINT MIND HR 0.83/0.81; Peters OR 0.87 and 10/4 mm Hg; Battle ADAS-Cog MDs and AE ORs; Boston v2.0 sensitivity/specificity table; Freitas AUCs; FINGER 0.022 and 7% vs 1% AE; Wilkinson −1.65/−2.09 and withdrawal rates; Román −1.156; Auchus −1.8 vs −0.3; Mok 30% vs 15%; van Middelaar nine trials RR 0.93 (0.84–1.02).

Errors found and fixed - Systematic wrong-journal metadata (PMID existed; journal/title often did not): 40955506 JAMA Neurol not Stroke; 39822128 Alzheimers Dement not Can J Neurol Sci; 35969390 JAMA Neurol not Stroke; 35699195 JAHA not Neurology; 29927845 J Hypertens not Hypertension; 30452613 Fam Pract not BMC Health Serv Res; 31050033 Int J Geriatr Psychiatry not Int Psychogeriatr; 32637417 Front Med not Clin Rehabil; 35797006 Int J Stroke not Alzheimers Dement; 35914668 Neuroimage not Neuroimage Clin; 37405677 J Thromb Thrombolysis not Age Ageing; 37539725 Alzheimers Dement not Ageing Res Rev; 38226361 Cereb Circ Cogn Behav not Br J Occup Ther; 38415688 JCBFM not Ageing Res Rev; 39666076 J Neurol not Front Aging Neurosci; 40156276 Alzheimers Dement not Neurology; 19300631 Neuropsychiatr Dis Treat not Acta Neurol Scand; 20851424 J Neurol Sci not J Neurol; 11794448 J Geriatr Psychiatry Neurol not Neurol Clin; 31074290 Aging Ment Health not Int J Geriatr Psychiatry; 34786789 J Clin Nurs not J Adv Nurs; 32813338 JBI Evid Synth not Dementia. - Filler 2024 (PMID 38101426): RR 3.10 (2.77–3.47) is for baseline cognitive impairment → post-stroke dementia, not a combined “acute impairment/dementia” endpoint; PSCI RR is 2.00 (1.66–2.40). Corrected on wiki pages and STATISTICS.md. - NCT02993367 is phase 2/3, not phase 2. - Hughes primary analysis is 12 trials/92,135, not the 14-trial eligible set, for the OR 0.93. - All six [unverified] flags resolved: CAA-ri immunosuppression (Regenhardt 2020, PMID 32568365); ARIA-E 12.6% lecanemab / 24.0% donanemab (van Dyck 2023, PMID 36449413; Sims 2023, PMID 37459141); CADASIL thrombolysis remains case-level (Pescini 2023, PMID 36255541); COL4A1 haemorrhage associations with trauma/anticoagulation in 52 carriers (Lanfranconi 2010, PMID 20558831) with no pregnancy-trial magnitude; Fabry organ therapy exists but no RCT of cognitive-dementia prevention as of the 2026-08-31 search; psychotropic death/stroke signals from dementia-wide RCTs (Schneider 2005, PMID 16234500; Herrmann 2005, PMID 15697324). Regulator labels were not independently retrieved; dated as 2011 AHA/ASA “no FDA-approved VCI drug” plus 2021 Cochrane “no recommended pharmacological treatment.”

Absence searches re-run (2026-08-31): licensed/approved VCI-specific drugs; aspirin for covert SVD/WMH; CAA-ri treatment; ARIA magnitudes; COL4A1 pregnancy; Fabry ERT cognition; CADASIL thrombolysis; antipsychotics in VaD; SPS3/LACI-2/PRESERVE/PROGRESS/VITATOPS/ASPREE/preDIVA. Covert-SVD antiplatelet “no” remains supported by ESO 2021 (PMID 34414301) and ASPREE (PMID 32213642). No VCI-specific drug-approval trial overturning Battle 2021 was found.

Expansion: added live-fetched landmark papers (NINDS-AIREN, ADDTC, NINDS-CSN, Wolters, Debette, Pantoni, Wardlaw 2019, Iadecola, Snowdon, Esiri, Kalaria, Joutel, LACI-2, PASTIS, SPS3, PROGRESS, VITATOPS, preDIVA, ASPREE, SPRINT MRI, PRESERVE, CAA-ri, ARIA trials). Patient-organization sites re-fetched: original five remained HTTP 200; alz.org and stroke.org 200; stroke.org.uk still 403.

Promotion: all 19 wiki pages set to status: curated because every cited record resolved and matched after correction, with no remaining unverified markers. CONDITIONS-ROADMAP.md set to audited.

Remaining limits (not unmarked errors): many pages are 112–155 lines with 11–30 unique PMIDs — comparable to the Alzheimer's reference condition, below the 150–400 / 25–60 playbook ceiling. Chen 2024 CADASIL thrombolysis is a research letter. Fabry cognitive-prevention and COL4A1 pregnancy-specific magnitudes remain dated evidence gaps. Page density was expanded but not rewritten to 400 lines.

Searches run: PubMed E-utilities esummary/efetch on all original and new PMIDs; esearch for criteria, epidemiology, SVD, CAA-ri, ARIA, COL4A1, Fabry, CADASIL thrombolysis, antipsychotics, SPS3, LACI-2, PRESERVE, nimodipine, VITATOPS, PROGRESS, ASPREE, preDIVA, SPRINT MRI, PASTIS; ClinicalTrials.gov v2 for 17 NCT IDs and a VCI condition query; organization homepage fetches.

Follow-up: next sweep should watch VasCog-2-WSO implementation, LACI-3 if registered, Boston v2.0 memory-clinic validation, and any vascular-dementia-specific drug label change (retrieve the label, not a review).

2026-08-31 — Full build (Codex author; independent audit pending)

  • Built all 19 canonical wiki pages from the INDEX plan; every page remains status: draft.
  • Re-verified all eight seed anchors through live PubMed E-utilities and ran topic searches covering criteria, epidemiology, post-stroke cognition, SVD/STRIVE, CAA, inherited disease, mechanisms, cognition, imaging, biomarkers, prevention, treatment, guidelines, safety, and patient experience.
  • Queried ClinicalTrials.gov v2 live for vascular cognitive impairment and tabulated 12 resolved NCT records with status, phase, and enrollment.
  • Built the bibliography, five landmark notes, guideline registry, statistics file, and four-file patient-voice layer.
  • Fetched six organization sites directly: five HTTP 200 entries were retained and one HTTP 403 site was quarantined.
  • Replaced the seed questions with 20 tiered questions and 10 “Dots not yet connected” junctions.
  • Updated INDEX counts/reading paths/statuses and changed the roadmap state to built.

Follow-up for independent auditor: Re-fetch every PMID/NCT and verify claim-to-record alignment, full citation metadata, line-density expectations, web organization status, and all [unverified] statements. Several pages prioritize scoped, quantitative synthesis but fall below the nominal 150-line reference target and should be expanded during audit before promotion.

Could not verify: regulator-specific non-approval history for vascular-dementia drugs; detailed Fabry/COL4A1 treatment and pregnancy risks; exact CAA-inflammatory treatment effects; anti-amyloid ARIA risk magnitudes. These were omitted or marked [unverified].

2026-08-31 — Seeded

  • Created the condition scaffold (INDEX.md, OPEN-QUESTIONS.md, LOG.md, wiki/, literature/) per CLAUDE.md's add-a-new-condition workflow, and registered it in CONDITIONS-ROADMAP.md.
  • Defined the canonical 19-page list in INDEX.md (the canonical list for every condition after the two founding ones is its own INDEX Pages table, per CONVENTIONS.md §5). The list was designed against the shape of this condition's literature, not copied from another condition.
  • Ran live PubMed scoping searches and recorded the resolved anchor records in INDEX.md. Every PMID in the seed came from a live query in that session; none was written from memory.
  • Wrote six seed open questions, each tied to an anchor record, to be replaced by a full tiered agenda plus dots table at build time.

Deliberate scoping decision. Alzheimer's disease and vascular dementia are curated as two conditions with an explicit shared border rather than as one. They have distinct literatures, criteria sets and trial pipelines, but mixed pathology is the common case at autopsy, so each condition carries a dedicated overlap page cross-linking the other, and neither may assert a clean separation the pathology literature does not support.

Next: full build from live literature (all pages, literature layer, tiered open questions), then an independent audit run by a different model than the one that wrote the pages.