Statistics — vascular dementia and vascular cognitive impairment¶
Last updated: 2026-09-02 (second deepening pass; eleven sections and twelve conflict rows added, to 34 sections and 27 conflicts). Conflicting estimates are preserved side by side. Every row includes population, method, and a live-resolved PMID.
Global all-dementia context¶
| Measure | Estimate | Year/population | Method | Source |
|---|---|---|---|---|
| people living with dementia | 57.4m (50.4–65.1) | global, 2019 | GBD modeling | PMID 34998485 |
| forecast prevalence | 152.8m (130.8–175.9) | global, 2050 | demographic/risk forecast | PMID 34998485 |
These are not vascular-dementia-specific totals.
Pre- and post-stroke dementia¶
| Measure | Estimate (95% CI) | Population | Method | Source |
|---|---|---|---|---|
| pre-stroke dementia | 14.4% (12.0–16.8) | hospital cohorts | systematic review/meta-analysis | PMID 19782001 |
| pre-stroke dementia | 9.1% (6.9–11.3) | population cohorts | same | PMID 19782001 |
| early post-stroke dementia | 7.4% (4.8–10.0) | first-ever stroke, prior dementia excluded | same | PMID 19782001 |
| early post-stroke dementia | 41.3% (29.6–53.1) | recurrent stroke, prior dementia included | same | PMID 19782001 |
| later cumulative incidence | 3.0% (1.3–4.7) per year | hospital cohorts after year 1 | same | PMID 19782001 |
| MCI among recent lacunar stroke | 47% | SPS3 English-speaking baseline, n=1,636 | neuropsychological z ≤ −1.5 | PMID 23034910 |
| WMH → incident stroke | HR 3.3 (2.6–4.4) | 22-study meta-analysis | longitudinal MRI | PMID 20660506 |
| WMH → incident dementia | HR 1.9 (1.3–2.8) | same | same | PMID 20660506 |
| WMH → death | HR 2.0 (1.6–2.7) | same | same | PMID 20660506 |
| any post-stroke NCD | 53.4% (46.9–59.8) | 16 hospital studies/3,087 | meta-analysis | PMID 30504699 |
| mild post-stroke NCD | 36.4% (29.0–43.8) | same | meta-analysis | PMID 30504699 |
| major post-stroke NCD | 16.5% (12.1–20.8) | same | meta-analysis | PMID 30504699 |
Predictors¶
| Predictor | Effect | Population/method | Source |
|---|---|---|---|
| baseline cognitive impairment → later post-stroke dementia | RR 3.10 (2.77–3.47) | 89-study meta-analysis; 160,783 patients | PMID 38101426 |
| baseline cognitive impairment → later post-stroke cognitive impairment | RR 2.00 (1.66–2.40) | same | PMID 38101426 |
| diabetes → later post-stroke cognitive impairment | RR 1.29 (1.14–1.45) | same | PMID 38101426 |
| AF (presence/history) → later post-stroke cognitive impairment | RR 1.29 (1.04–1.60) | same | PMID 38101426 |
| moderate/severe WMH → later post-stroke cognitive impairment | RR 1.51 (1.20–1.91) | same | PMID 38101426 |
Autopsy composition¶
| Pathology category | Share among dementia cases | Population/method | Source |
|---|---|---|---|
| Alzheimer pathology + infarcts | 38.0% | community autopsy cohort | PMID 17568013 |
| Alzheimer pathology alone | 30.0% | same | PMID 17568013 |
| vascular dementia alone | 12% | same | PMID 17568013 |
Blood-pressure prevention¶
| Outcome | Effect (95% CI) | Population/method | Source |
|---|---|---|---|
| probable dementia, intensive vs standard | HR 0.83 (0.67–1.04) | SPRINT MIND RCT | PMID 30688979 |
| MCI, intensive vs standard | HR 0.81 (0.69–0.95) | SPRINT MIND RCT | PMID 30688979 |
| dementia/cognitive impairment | OR 0.93 (0.88–0.98); ARR 0.39% | 12 RCTs/92,135; mean 4.1y | PMID 32427305 |
| dementia | OR 0.87 (0.75–0.99) | 5-trial IPD/28,008 | PMID 36282295 |
| dementia | RR 0.93 (0.84–1.02) | 9 RCTs (1,041/29,029 vs 1,090/28,653) | PMID 29927845 |
| PROGRESS dementia | RRR 12% (−8 to 28) | 6,105 prior stroke/TIA; 3.9 y | PMID 12742805 |
| PROGRESS cognitive decline | RRR 19% (4–32) | same | PMID 12742805 |
| preDIVA dementia | HR 0.92 (0.71–1.19) | 3,526 adults 70–78; 6.7 y | PMID 27474376 |
| ASPREE dementia trigger | HR 1.03 (0.91–1.17) | 19,114; aspirin 100 mg; 4.7 y | PMID 32213642 |
| SPRINT MRI WMH growth | −0.54 cm³ (−0.87 to −0.20) intensive vs standard | n=449 paired MRI | PMID 31408137 |
| LACI-2 ISMN cognitive impairment | aOR 0.55 (0.36–0.86) | 363 lacunar stroke; 1 y | PMID 37222252 |
Symptomatic cognitive drugs¶
| Intervention | Cognitive effect vs placebo | Adverse-event effect | Method | Source |
|---|---|---|---|---|
| donepezil 5 mg | ADAS-Cog MD −0.92 (−1.44 to −0.40) | OR 1.22 (0.94–1.58) | network meta-analysis | PMID 33704781 |
| donepezil 10 mg | MD −2.21 (−3.07 to −1.35) | OR 1.95 (1.20–3.15) | same | PMID 33704781 |
| galantamine 16–24 mg | MD −2.01 (−3.18 to −0.85) | OR 1.57 (1.02–2.43) | same | PMID 33704781 |
| rivastigmine 3–12 mg | MD 0.03 (−3.04 to 3.10) | OR 3.21 (0.36–28.88) | same | PMID 33704781 |
| donepezil 5/10 mg | −1.65/−2.09 ADAS-Cog | withdrawal 10.1%/16.3% vs 8.8% | 616-person RCT, 24 weeks | PMID 12939421 |
| galantamine | ADAS-Cog −1.8 vs −0.3 | discontinuation 13% vs 6% | 788-person RCT, 26 weeks | PMID 17664404 |
CAA diagnostic accuracy¶
| Cohort | Sensitivity | Specificity | Source |
|---|---|---|---|
| Boston v2.0 derivation | 74.8% (65.4–82.7) | 84.6% (71.9–93.1) | PMID 35841910 |
| temporal validation | 92.5% (79.6–98.4) | 89.5% (66.9–98.7) | PMID 35841910 |
| geographic validation | 80.2% (70.8–87.6) | 81.5% (61.9–93.7) | PMID 35841910 |
| autopsy standard | 74.5% (65.4–82.4) | 95.0% (83.1–99.4) | PMID 35841910 |
| Boston v2.0 probable CAA, non-haemorrhagic | 28.6% (13.2–48.7) | 65.3% (44.3–82.8) | PMID 38710005 |
| lecanemab ARIA-E | 12.6% | CLARITY-AD n=898 treated | PMID 36449413 |
| donanemab ARIA-E | 24.0% (52 symptomatic) | TRAILBLAZER-ALZ 2 n=860 treated | PMID 37459141 |
| CAA-ri clinical improvement with immunosuppression | 94% vs 50% untreated (OR 16.0, 2.72–94.1) | 48-person observational series | PMID 32568365 |
| atypical antipsychotic death in dementia RCTs | OR 1.54 (1.06–2.23); 3.5% vs 2.3% | 15 trials, 5,110 randomized | PMID 16234500 |
Cognitive screening¶
| Instrument | Accuracy | Population/method | Source |
|---|---|---|---|
| full MoCA | AUC 0.950 (0.868–0.988) | 34 VaD patients, single validation | PMID 22676901 |
| short MoCA | AUC 0.936 (0.849–0.981) | same | PMID 22676901 |
| MMSE | AUC 0.860 (0.754–0.932) | same | PMID 22676901 |
| MoCA for VMCI | AUC range 0.87–0.93 | systematic review; heterogeneous | PMID 31050033 |
Community incidence of vascular dementia (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/year | Method | Source |
|---|---|---|---|---|
| vascular-dementia incidence | 1.5 per 1,000 person-years | Rotterdam Study, 7,046 dementia-free adults ≥55, 15,135 person-years, 1990–1993 baseline | three-stage screening, prospective cohort | PMID 9521184 |
| all-dementia incidence | 10.7 per 1,000 person-years | same | same | PMID 9521184 |
| all-dementia incidence by age band | 0.6 → 97.2 per 1,000 py across 5-year bands | same | same | PMID 9521184 |
| lifetime dementia risk from age 55 | 0.33 women / 0.16 men | same | Kaplan-Meier from incidence | PMID 9521184 |
| vascular-dementia incidence | 1.4 (0.6–2.3) per 1,000 person-years | NEDICES, central Spain, 3,891 followed a median 3.2 y | European-standardized, population survey | PMID 17727890 |
| all-dementia incidence | 10.6 (8.9–12.3) per 1,000 person-years | same | same | PMID 17727890 |
| VaD share of incident dementia | 11.2% (18/161 cases; AD 71.4%) | same | same | PMID 17727890 |
| cumulative vascular-dementia risk to age 95 | 0.04 in both sexes | EURODEM, 4 European cohorts, 528 incident cases, 28,768 person-years | pooled Poisson/log-linear | PMID 10599770 |
| cumulative Alzheimer risk to age 95 (from 65) | 0.22 women / 0.09 men | same | same | PMID 10599770 |
| AD incidence at age 90 | 81.7 (63.8–104.7) women vs 24.0 (10.3–55.6) men per 1,000 py | same | same | PMID 10599770 |
| vascular-dementia prevalence (primary or contributing) | 4.2% (AD 5.4%; AD/VaD ratio 1.5) | Honolulu-Asia Aging Study, 3,734 Japanese-American men aged 71–93 | age-standardized prevalence 7.6% overall | PMID 8805729 |
| >1 possible cause of dementia | 26% of cases | same | same | PMID 8805729 |
Mortality and cost (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/method | Source |
|---|---|---|---|
| any dementia vs no dementia, all-cause mortality | HR 5.90 (3.53–9.86) | 78 studies; 63,125 with dementia, 152,353 controls | PMID 36097997 |
| non-Alzheimer vs Alzheimer dementia, all-cause mortality | HR 1.33 (1.21–1.46) | same | PMID 36097997 |
| survival from diagnosis, Alzheimer disease | mean 5.8 years (SD 2.0) | same | PMID 36097997 |
| survival from diagnosis, non-Alzheimer vs Alzheimer | −1.12 years (−1.52 to −0.72) | same | PMID 36097997 |
| survival from onset, vascular dementia vs Alzheimer | −1.27 years (−1.90 to −0.65) | same; only VaD and DLB reached significance | PMID 36097997 |
| Lewy body dementia mortality (highest of all subtypes) | HR 17.88 (5.87–54.46) | same | PMID 36097997 |
| informal care hours, 24 brain health disorders | 9.4 billion (7.8–11.3) hours, 2021 | 204-country modelling study | PMID 41748237 |
| forgone earnings from informal care | US$1.7 trillion (1.5–2.1), 2021 | same; stroke = most hours, dementia = most lost earnings | PMID 41748237 |
| annual growth in informal care hours since 2000 | 3.2% (2.9–3.5) | same | PMID 41748237 |
| vascular dementia in AF with low conventional stroke risk | HR 1.68 (1.33–2.12) vs matched non-AF controls | 36,340 AF vs 117,298 controls, UK primary care, median 5 y | PMID 38839900 |
| all-cause dementia in the same cohort | HR 1.17 (1.04–1.32); Alzheimer HR 0.85 (0.70–1.03) | same | PMID 38839900 |
Post-stroke cognitive trajectory and prediction (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/method | Source |
|---|---|---|---|
| trajectory-group membership at ~3.6 months | low −3.27 SD (17%), medium −1.23 SD (48%), high +0.71 SD (35%) | STROKOG, 1,149 patients, 9 hospital cohorts, latent-class growth analysis | PMID 37072222 |
| change over year 1, high-performance group | +0.22 SD/year (0.07–0.36) | same; low and medium groups not significant | PMID 37072222 |
| large-artery vs small-vessel stroke → low-performance group | RRR 2.77 (1.32–5.83) | same | PMID 37072222 |
| diabetes → low-performance group | RRR 3.78 (2.08–6.88) | same | PMID 37072222 |
| global cognitive decline beyond 1 year post-stroke | −0.053 SD/year (−0.073 to −0.033) | STROKOG IPD, 1,488 patients, median 2.68 y | PMID 34775838 |
| excess decline vs stroke-free controls | −0.078 SD/year (−0.11 to −0.045) | same, subgroup analysis | PMID 34775838 |
| post-stroke dementia incidence | 8.7 per 100 person-years (655/2,663 over median 2.0 y) | STROKOG, 12 studies, 10 countries | PMID 41525568 |
| 5-year post-stroke dementia model discrimination | C 0.81 (0.75–0.87) development; 0.70 (0.67–0.73) internal-external validation | Fine-Gray with death as competing risk | PMID 41525568 |
| CAIDE score applied to stroke cohorts | AUC 0.53 | 4 harmonized cohorts, 12–18 months | PMID 32568644 |
| ANU-ADRI applied to stroke cohorts | C 0.66 | same | PMID 32568644 |
| Brief Dementia Screening Indicator in stroke cohorts | C 0.61 | same | PMID 32568644 |
| OCS-based 6-month PSCI model | C 0.76 (0.71–0.80) internal; 0.74 (0.68–0.80) external | 430 development + external OCS-Care validation | PMID 41794047 |
Criteria performance against autopsy (added 2026-08-31)¶
| Criteria | Sensitivity | Specificity | Population | Source |
|---|---|---|---|---|
| ADDTC possible VaD | 0.63 | 0.64 | 113 autopsied demented patients | PMID 9305324 |
| NINDS–AIREN possible VaD | 0.58 | 0.80 | same | PMID 9305324 |
| Hachinski Ischemic Score | 0.43 | 0.88 | same | PMID 9305324 |
| ADDTC possible VaD | 0.70 | 0.78 | 89 autopsied (20 VaD, 23 mixed, 46 AD) | PMID 11772694 |
| NINDS–AIREN possible VaD | 0.55 | 0.84 | same | PMID 11772694 |
| DSM-IV vascular dementia | 0.50 | 0.84 | same | PMID 11772694 |
| ADDTC probable VaD | 0.25 | 0.91 | same | PMID 11772694 |
| NINDS–AIREN probable VaD | 0.20 | 0.93 | same | PMID 11772694 |
| ICD-10 vascular dementia | 0.20 | 0.94 | same | PMID 11772694 |
| ADDTC / NINDS–AIREN / HIS possible VaD | 0.56–0.58 (all three) | 0.74 / 0.73 / 0.66 | 110 autopsies in the oldest-old, 36 confirmed VaD | PMID 16580095 |
| mixed dementia misclassified as VaD | ADDTC 54%, NINDS–AIREN 29%, HIS 18% | — | 113 autopsies | PMID 9305324 |
| pure VaD cases in the oldest-old with no stroke history | 42% | — | 110 autopsies | PMID 16580095 |
| interrater reliability, 4 criteria sets | κ 0.30 (ADDTC) to 0.61 (original HIS) | 25 case vignettes, 7 centres | PMID 10681076 |
Neuropathologic composition, large series (added 2026-08-31)¶
| Measure | Estimate | Population/method | Source |
|---|---|---|---|
| participants with ≥1 neuropathology | 94% (≥2: 78%; ≥3: 58%; ≥4: 35%) | 1,079 autopsied with 2+ cognitive evaluations | PMID 29244218 |
| Alzheimer disease occurring in isolation | 9% (present in 65%) | same | PMID 29244218 |
| distinct neuropathologic combinations observed | >230, each in <6% of cohort | same | PMID 29244218 |
| person-specific share of cognitive loss due to AD | mean ~50%; individual range 22–100% | same | PMID 29244218 |
| decedents with any cerebrovascular pathology | 80% (of these, 37% single, 63% mixed) | 1,474 Rush decedents, 32 CVD combinations | PMID 34601898 |
| faster decline vs no CVD | mixed CVD profiles only; single CVD profiles did not differ | same | PMID 34601898 |
| participants with mixed pathology | >80%; 280 unique copathology combinations | 1,633 ROS/MAP decedents, mean age at death 90.4 | PMID 41543852 |
| empirical neuropathologic profiles | infarcts+vessel disease 15.9%; LATE-NC+hippocampal sclerosis 12.3%; Lewy bodies 21.7%; ADNC+CAA 9.7%; low pathology 40.4% | same, hierarchical clustering | PMID 41543852 |
Small-vessel disease markers and progression (added 2026-08-31)¶
| Measure | Effect (95% CI) | Population/method | Source |
|---|---|---|---|
| baseline WMH volume → dementia | HR 1.31 per SD (1.02–1.67) | RUN DMC, 503 sporadic SVD, median 13.2 y | PMID 37073486 |
| DWI-positive lesions → dementia | HR 2.03 (1.01–4.04) | same | PMID 37073486 |
| PSMD → dementia | HR 1.24 per SD (1.02–1.51) | same | PMID 37073486 |
| WMH progression → dementia | HR 1.76 per SD (1.18–2.63) | same | PMID 37073486 |
| dementia incidence in sporadic SVD | 108/498 (21.5%) over median 13.2 y | same (AD 38, VaD 34, mixed 26) | PMID 37073486 |
| genetically determined WMH → Alzheimer disease | OR 1.43 (1.10–1.86) | two-sample MR, up to 75,024 AD cases | PMID 38776079 |
| genetically determined WMH → incident all-cause dementia | HR 1.02 (1.00–1.04), null | individual-level longitudinal, 10,699 cases | PMID 38776079 |
| systolic BP → lacunar stroke | OR 1.41 (1.30–1.54) | MR, GWAS n=757,601 exposure | PMID 38818733 |
| genetically proxied CCB → WMH volume | β −0.287 (−0.408 to −0.165) | same | PMID 38818733 |
| genetically proxied CCB → basal-ganglia PVS | OR 0.85 (0.81–0.89) | same | PMID 38818733 |
| enlarged perivascular spaces → MMSE | 0.001 (−0.007 to 0.008), null | UNIVRSE, 5 population cohorts, 3,575 people | PMID 30068634 |
| enlarged perivascular spaces → general cognitive factor | 0.002 (−0.001 to 0.006), null | same | PMID 30068634 |
| chronic cortical microinfarct prevalence | 35% (24–49%) | RUN DMC-Intense, 54 SVD patients, monthly 3T MRI | PMID 32065609 |
| acute cortical microinfarct cumulative incidence | 13% (6–24%); all disappeared on follow-up MRI | same, 472 DWI scans over median 39.5 weeks | PMID 32065609 |
| intensive vs standard BP → global SVD factor change | Cohen's d −0.40 (−0.62 to −0.17) | SPRINT MRI substudy, 442 with paired scans, median 3.9 y | PMID 42614618 |
| dose-response by attained SBP reduction | 21.2% (7.4–35.0) / 26.3% (13.1–39.5) / 39.4% (24.2–54.5) less progression for 0–10 / 10–20 / ≥20 mm Hg | same | PMID 42614618 |
Biomarker validation (added 2026-08-31)¶
| Marker | Result | Population/method | Source |
|---|---|---|---|
| PSMD → general cognition | β −0.8 (−1.2 to −0.4); explains cognition beyond WMH | MarkVCID-1 n=396, replicated in CHARGE (6,172), Rush (287), UC Davis (567) | PMID 39569745 |
| MRI free water → executive composite | associated cross-sectionally; predicted accelerated decline (P=0.0026) over ~1.29 y | MarkVCID sub-cohorts + 5 legacy cohorts | PMID 36523847 |
| cerebrovascular reactivity → MoCA and executive IRT | positive at all 3 sites, prespecified hypothesis | MarkVCID, n=263, 5% CO₂ | PMID 38951718 |
| WMH growth/regression protocol reliability | test-retest ICC 0.969 (growth) / 0.937 (regression); cross-site ICC 0.995 / 0.990 | MarkVCID multi-site | PMID 37840499 |
| WMH growth → memory | associated (P<0.028); WMH regression not associated with any outcome | same | PMID 37840499 |
| plasma NfL | strongest association with SVD burden (WMH, MSMD, fiber density) | 76 memory-clinic patients; 41 ADNI validation | PMID 42252508 |
| plasma p-tau217 | strongest association with AD-related neurodegeneration | same | PMID 42252508 |
| plasma GFAP | associated with both SVD and AD markers | same; WMH association replicated in MESA | PMID 42252508, 41630612 |
| plasma Aβ42/40 | lower ratio associated with amyloid PET and with microbleeds | MESA, n=251 | PMID 41630612 |
Haemorrhage risk and anticoagulation (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/method | Source |
|---|---|---|---|
| symptomatic ICH on anticoagulation, microbleeds present | 9.8 per 1,000 patient-years (4.0–20.3) | CROMIS-2, 1,447 AF + recent stroke/TIA, 3,366 patient-years | PMID 29778365 |
| symptomatic ICH, no microbleeds | 2.6 per 1,000 patient-years (1.1–5.4); adjusted HR 3.67 (1.27–10.60) | same | PMID 29778365 |
| HAS-BLED discrimination for symptomatic ICH | C 0.41 (0.29–0.53) | same | PMID 29778365 |
| HAS-BLED + microbleeds | C 0.66 (0.53–0.80) | same | PMID 29778365 |
| HAS-BLED + microbleeds + diabetes + anticoagulant type | C 0.74 (0.60–0.88) | same | PMID 29778365 |
| >10 basal-ganglia perivascular spaces → symptomatic ICH | HR 8.96 (2.41–33.4) on 14 events | CROMIS-2 post hoc, 1,386 participants, mean 2.34 y | PMID 32934168 |
| starting vs avoiding anticoagulation after intracranial haemorrhage: recurrence | 8/101 (8%) vs 4/102 (4%); adjusted HR 2.42 (0.72–8.09) | SoSTART RCT, 67 UK hospitals | PMID 34487722 |
| pooled: any stroke or cardiovascular death | HR 0.68 (0.42–1.10), I²=0% | COCROACH IPD meta-analysis, 412 participants, 4 trials | PMID 37839434 |
| pooled: ischaemic major adverse cardiovascular events | 9/212 (4%) vs 38/200 (19%); HR 0.27 (0.13–0.56) | same | PMID 37839434 |
| pooled: haemorrhagic major adverse cardiovascular events | 15/212 (7%) vs 9/200 (5%); HR 1.80 (0.77–4.21) | same | PMID 37839434 |
| CAA-related ICH recurrence | 23% (18–28%), I²=96.7% | 30-study meta-analysis | PMID 38020625 |
| disseminated cortical superficial siderosis → recurrence | OR 3.21 (2.25–4.58) | same | PMID 38020625 |
| cortical superficial siderosis → recurrent ICH (within RCT) | HR 7.7 (1.4–42.2) on 13 events | PRESTIGE-AF imaging subanalysis, n=313, median 1.4 y | PMID 41197104 |
| probable CAA category → recurrent ICH | not associated (P>0.2) | same | PMID 41197104 |
| Edinburgh CT-only criteria, 5-year recurrence | 12% low / 16% intermediate (aSHR 1.68, 1.21–2.32) / 26% high risk (aSHR 2.97, 1.50–5.89) | IPD meta-analysis, 1,620 patients, 8 cohorts | PMID 40975099 |
| LAAO in CAA-related ICH with AF: ischaemic stroke | 5.16 per 100 patient-years (1.36–17.48) | 102 pooled participants, median 9.4 months | PMID 39694822 |
| LAAO in CAA-related ICH with AF: ICH | 2.73 per 100 patient-years (0.41–13.94) | same | PMID 39694822 |
Prevention trials, expanded (added 2026-08-31)¶
| Trial / synthesis | Effect (95% CI) | Population/method | Source |
|---|---|---|---|
| Syst-Eur, double-blind phase | dementia 7.7 → 3.8 per 1,000 py (21 vs 11 cases, P=0.05); 50% reduction | 2,418 adults ≥60, isolated systolic hypertension, median 2.0 y, nitrendipine-based | PMID 9802273 |
| Syst-Eur, open extension | 7.4 → 3.3 per 1,000 py (43 vs 21 cases, P<0.001); adjusted HR 0.38 (0.23–0.64) | median 3.9 y; 20 dementias prevented per 1,000 treated 5 y (7–33) | PMID 12374512 |
| Cochrane antihypertensives, incident dementia | OR 0.89 (0.72–1.09), very low certainty | 4 placebo-controlled trials without prior cerebrovascular disease, 236/7,767 vs 259/7,660 | PMID 34028812 |
| Cochrane antihypertensives, MMSE | MD 0.20 (0.10–0.29), very low certainty | 5 placebo-controlled trials; contrast −9.25/−2.47 mm Hg | PMID 34028812 |
| antihypertensives, cognitive-function score | SMD 0.06 (0.03–0.09), GRADE moderate | 4 RCTs (Syst-Eur, PROGRESS, SCOPE, HYVET-COG), 16,823 participants — not the same four-trial set as Cunningham (PROGRESS included) | PMID 41962914 |
| antihypertensives, dementia incidence | OR 0.89 (0.76–1.05), GRADE low | same four-trial set as the Ding SMD row, not Cunningham | PMID 41962914 |
| drug-class ranking (exploratory, 1 study per node) | CCB highest for dementia prevention (SUCRA 94.7%); diuretic ± ACEi highest for cognitive improvement (SUCRA 95.3%) | same | PMID 41962914 |
| lipid-lowering therapy, incident cognitive impairment or dementia | OR 0.96 (0.74–1.26); 1.33% vs 1.36% over mean 34.5 months | 15 RCTs, 139,169 participants | PMID 40794911 |
| statins specifically | OR 0.90 (0.67–1.21) | same | PMID 40794911 |
| rhythm vs rate control, dementia | HR 0.74 (0.62–0.89), I²=62% | 14 studies, 193,830 AF patients, mostly observational | PMID 38369630 |
| AF ablation → vascular dementia | HR 0.58 (0.42–0.80), I²=31% | same | PMID 38369630 |
| US POINTER, structured vs self-guided | 0.243 vs 0.213 SD/y; difference 0.029 SD/y (0.008–0.050), P=0.008 | 2,111 randomized, 2 y, 89% completed | PMID 40720610 |
| LatAm-FINGERS, systematic vs flexible | 0.31 vs 0.20 SD/y; difference 0.11 SD/y (0.06–0.15), P<0.0001 | 1,065 across 11 Latin American countries, 2 y | PMID 42442374 |
| exercise and/or intensive vascular risk reduction, PACC | exercise 0.1 (−0.1 to 0.2), P=0.37; IRVR −0.1 (−0.3 to 0.03), P=0.12 (abstract prints unsigned 0.1; arm means +0.2 vs +0.3 imply a negative contrast); interaction P=0.13 | 513 randomized 2×2 factorial, 24 months | PMID 41870419 |
| ACHIEVE hearing intervention, 3-year cognition | difference 0.002 SD (−0.077 to 0.081), P=0.96 | 977 adults 70–84; prespecified cohort interaction P=0.010 | PMID 37478886 |
Drug trials, expanded (added 2026-08-31)¶
| Intervention | Effect (95% CI) | Population/method | Source |
|---|---|---|---|
| memantine 20 mg, MMM 300 | ADAS-Cog difference 2.0 points (0.49–3.60); CIBIC-plus 60% vs 52%, P=0.227 | 321 randomized / 288 ITT, France, 28 weeks | PMID 12105362 |
| memantine 20 mg, MMM500 | ADAS-Cog −1.75 (−3.02 to −0.49); CGI-C no difference | 579 randomized / 548 ITT, 54 UK centres, 28 weeks | PMID 12409683 |
| memantine, pooled | ADAS-Cog/11 MD −2.20 (−3.24 to −1.15), moderate certainty; GBS −1.93 (−4.69 to 0.84) | 2 trials, n=752 / n=595 | PMID 42635820 |
| galantamine, pooled | ADAS-Cog/11 −2.01 (−3.18 to −0.85); ADAS-Cog/13 −2.51 (−3.87 to −1.15); NPI −0.13 (−4.05 to 3.79) | 2 trials, n≈1,330 | PMID 42635820 |
| EGb 761, pooled | SKT −2.65 (−5.17 to −0.12), I²=92.8%, very low certainty | 3 trials, n=283 | PMID 42635820 |
| VaD placebo-controlled trials available | 16 trials, 5,668 participants; all but one published ≤2012 | systematic search 1990–2025 | PMID 42635820 |
| donepezil 5 mg (SMD framing) | SMD −1.11 (−1.88 to −0.34) | 11-RCT network meta-analysis | PMID 35048806 |
| donepezil 10 mg, CDR-SB / EXIT25 | −0.25 (−0.44 to −0.06) / −1.47 (−2.79 to −0.15) | same | PMID 35048806 |
| Cerebrolysin, cognition | SMD 0.36 (0.13–0.58), very low quality | Cochrane, 3 trials, 420 people | PMID 31710397 |
| Cerebrolysin, global response | RR 2.69 (1.82–3.98), very low quality | Cochrane, 2 trials, 379 people | PMID 31710397 |
| Cerebrolysin RCT | ADAS-Cog+ 10.6 vs 4.4 points (LS mean difference −6.17, P<0.0001); combined responders 67.5% vs 27.0% | 242 VaD participants, 24 weeks | PMID 20656516 |
| Actovegin (ARTEMIDA) | ADAS-Cog+ change −6.8 vs −4.6; difference −2.3 (−3.9 to −0.7), P=0.005 at 6 months | 503 randomized within 1 week of ischaemic stroke, MoCA ≤25 | PMID 28432265 |
| butylphthalide (NBP) | ADAS-Cog −2.46 vs −1.39, P=0.03; CIBIC-plus 57.1% vs 42.1%, P=0.01 | 281 subcortical VCIND, 15 Chinese centres, 24 weeks | PMID 26086183 |
| butylphthalide, Cochrane re-analysis | adjusted MD −1.07 (−2.02 to −0.12) ADAS-Cog-12, very low certainty | same trial re-assessed | PMID 35833913 |
| Ginkgo in dementia, SKT | MD −1.86 (−3.48 to −0.24), I²=96%, low certainty | Cochrane, 9 studies, 2,801 participants | PMID 41641880 |
| Ginkgo in dementia, ADL International Scale | MD −0.19 (−0.35 to −0.03), I²=91% | Cochrane, 8 studies, 2,571 | PMID 41641880 |
| Ginkgo in MCI, ADAS-Cog | MD −0.07 (−0.67 to 0.51), moderate certainty (no effect) | Cochrane, 2 studies, 508 | PMID 41641880 |
| Ginkgo serious adverse events in MCI | RR 0.95 (0.82–1.09), high certainty | Cochrane, 3 studies, 714 | PMID 41641880 |
| CONIVaD combination | all endpoints null; nimodipine adherence >75% dose in only 15% | 62 randomized, 12 months | PMID 33855653 |
| COMCID cilostazol | MMSE change −1.8 vs −1.3 at 96 weeks, null | 159 with MCI, MMSE 22–28, CDR 0.5 | PMID 38048134 |
| cilostazol, recurrent ischaemic stroke | OR 0.68 (0.57–0.81) | 17 trials, 10,225 participants, mostly Asia-Pacific | PMID 32646330 |
| cilostazol, haemorrhagic stroke | OR 0.43 (0.29–0.64) | 16 trials, 9,736 | PMID 32646330 |
| LACI-2 at 6 months, ISMN composite | adjusted OR 0.74 (0.55–0.99) | 363 lacunar stroke | PMID 42535538 |
| LACI-2 at 6 months, combination cognition | adjusted common OR 0.40 (0.21–0.78) | same | PMID 42535538 |
| OxHARP sildenafil, pulsatility (primary) | 0.02 (−0.01 to 0.05), P=0.18, null | 3-way crossover, 65 with valid data | PMID 38832504 |
| OxHARP sildenafil, cerebrovascular reactivity | 0.83 cm/s per mm Hg (0.23–1.42), P=0.007 | same | PMID 38832504 |
| MINERVA minocycline, microglial signal / BBB permeability | RR 1.01 (0.98–1.04) / RR 0.97 (0.91–1.03), both null | 44 SVD patients, 3 months | PMID 38629936 |
Imaging automation (added 2026-08-31)¶
| Measure | Result | Population/method | Source |
|---|---|---|---|
| automated WMH segmentation, SE-UNet Dice | 0.675 (0.666–0.685) internal; 0.722 (0.719–0.726) external | trained on 2,408 scans, validated on 6,013; 8,421 acute ischaemic stroke patients | PMID 39013565 |
| human–human Dice reliability (benchmark) | 0.744 (0.738–0.751) | same | PMID 39013565 |
| automated vs manual WMH volume correlation | r = 0.933 (SE-UNet); CCC 0.841–0.956 externally | same | PMID 39013565 |
| cases below uncertainty index 0.35 | 86% of external cases, mean Dice 0.744 | same | PMID 39013565 |
| ML models on SVD markers, controls vs Alzheimer dementia | AUC 0.88 (0.85–0.92) | meta-analysis of 16 of 75 eligible studies | PMID 40775365 |
| ML models on SVD markers, controls vs cognitive impairment | AUC 0.84 (0.74–0.95) | same | PMID 40775365 |
| studies testing external generalisability | 5 of 75 | same | PMID 40775365 |
Monogenic disease frequency (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/method | Source |
|---|---|---|---|
| genetically confirmed clinical CADASIL prevalence | 1.98 per 100,000 adults (1.24–3.00) | west of Scotland register, 22 cases in 7 pedigrees | PMID 15834040 |
| predicted NOTCH3 mutation carrier prevalence | 4.14 per 100,000 adults (3.04–5.53) | same, adding 37 predicted carriers | PMID 15834040 |
| CADASIL prevalence, later Glasgow series | 4.6 per 100,000 adults; mutation prevalence 10.7 per 100,000 | 49 pedigrees, 21 NOTCH3 mutations (61% exon 4) | PMID 24840674 |
| median age at first stroke, women | 57 years | same | PMID 24840674 |
| median age at first stroke, men by diagnosis era | 46 y (pre-2006) → 56 y (post-2006), P=0.034 | same | PMID 24840674 |
| genetic CADASIL prevalence | 1 in 277 individuals | 129,933 healthy Korean adults, NGS of 3 NOTCH3 variants | PMID 40982447 |
| NOTCH3 allele frequencies (Korean) | p.Arg544Cys 0.07%, p.Arg640Cys 0.07%, p.Arg75Pro 0.04% | same | PMID 40982447 |
| high-risk EGFr domains → stroke in community carriers | OR 10.81 (5.46–21.37) | 2,574 CADASIL patients + 1,647 population; validated in 434 + 1,003 | PMID 36535904 |
| medium-risk EGFr domains → stroke | OR 1.81 (0.84–3.88) | same | PMID 36535904 |
| risk metric vs NOTCH3 aggregation load / signalling activity | P=0.006 / P=0.88 | same | PMID 36535904 |
Cognitive screening across populations (added 2026-08-31)¶
| Measure | Result | Population/method | Source |
|---|---|---|---|
| optimal MoCA cutoff in less-WEIRD populations | lower than in WEIRD populations | systematic review: 28 MMSE, 39 MoCA, 5 OCS accuracy studies, 17 countries | PMID 37480233 |
| optimal MMSE and OCS subtest cutoffs | similar across WEIRD and less-WEIRD populations | same | PMID 37480233 |
| accuracy studies in South American, African, non-Chinese Asian stroke populations | none identified | same | PMID 37480233 |
| OCS normative sample / acute stroke characterization | 140 healthy participants / 208 acute stroke patients within 3 weeks | development and validation study | PMID 25730165 |
| OCS memory and receptive-communication subtests | impairment rates lower than expected → relatively insensitive | independent evaluation, 316 acute-stroke-unit patients | PMID 37186035 |
Patient-reported burden (added 2026-08-31)¶
| Measure | Estimate (95% CI) | Population/method | Source |
|---|---|---|---|
| stroke survivors with any unmet need ≥12 months post-stroke | 84% (median 4 of 20 domains) | 765 community-dwelling Australian survivors | PMID 25042019 |
| greater disability → unmet need, work domain | aOR 7.0 (3.0–17.0) | same | PMID 25042019 |
| memory problems → unmet need, leisure domain | aOR 2.1 (1.0–4.2) | same | PMID 25042019 |
| being 1–2 years post-stroke → unmet need, work domain | aOR 3.4 (1.5–7.8) | same | PMID 25042019 |
| CADA-PRO internal consistency / test-retest | Cronbach α 0.95 / ICC 0.88 | developed in 44, validated in 89 (43 CADASIL, 46 other SVD) | PMID 39234671 |
| CADA-PRO correlations in non-CADASIL SVD | only with HADS and Starkstein Apathy Scale | same | PMID 39234671 |
| psychoeducation studies covering non-language cognitive domains | very few of 30 included studies | scoping review, 1996–2023, 9 high-income countries | PMID 39819901 |
Vascular-dementia-specific prevalence and incidence, by country (added 2026-09-02)¶
| Measure | Estimate (95% CI) | Population / year | Method | Source |
|---|---|---|---|---|
| vascular dementia prevalence | 1.6% (1.5–1.7); 3.92m cases (3.64–4.22) | China, ≥60 y, 2015–2018, n=46,011 | national multistage stratified cluster survey with in-person testing | PMID 33271079 |
| vascular dementia prevalence | 0.96% (0.63–2.1) | China, ≥18 y, 26 studies, 100,923 subjects, 1999–2019 | meta-analysis including Chinese-language databases | PMID 34178760 |
| vascular cognitive impairment prevalence | 1.54% (1.14–1.93); 2.91% at ≥80 y | China, 81 studies, 784,846 participants, 1980–2023 | random-effects meta-analysis, I²>90% | PMID 40889799 |
| vascular cognitive impairment incidence | 0.29 per 100 person-years (0.21–0.41) | China, 10 incidence studies | same | PMID 40889799 |
| vascular dementia prevalence | 116 per 10,000 (86–157) | community, ≥50 y, 47 studies | meta-analysis by region, age, sex | PMID 31884487 |
| vascular dementia prevalence, sex ratio at 60–69 y | 56 per 10,000 men vs 32 per 10,000 women (1.8×) | community | same | PMID 31884487 |
| vascular dementia incidence | 9.5 / 1,000 py (AD 14.6; combined 3.8; DLB 1.4) | Hisayama, Japan, 828 adults ≥65, 17 y, 91.2% morphologically evaluated | prospective community cohort with autopsy | PMID 18977814 |
| 10-year survival, dementia vs matched controls | 13.6% vs 29.3%; HR 1.67 (1.31–2.13) | Hisayama, ages 65–89 | same; no significant difference between subtypes | PMID 18977814 |
| "pure" vascular dementia share of demented autopsies | 12.3% overall; 15.0% at age 60 falling to 8.7% at 90+ | 1,700 consecutive Vienna autopsies, mean age 84.3 | hospital autopsy series, consensus criteria | PMID 21504129 |
Do not average the three Chinese estimates. A pooled VCI prevalence (1.54%) that is no higher than a national VaD prevalence (1.6%) is internally inconsistent; the denominators (≥18 vs ≥60), the criteria, and the ascertainment differ. The Hisayama incidence is roughly six times the Rotterdam and NEDICES figures in the community-incidence section above, despite stronger (91% morphological) case verification.
Cost of vascular dementia (added 2026-09-02)¶
| Measure | Estimate | Population / year | Method | Source |
|---|---|---|---|---|
| annual direct healthcare cost, vascular dementia | US$14,387 | 100,000-member US Medicare HMO, 1999–2002 | administrative claims | PMID 16155348 |
| annual direct cost, other dementias / AD / CVD-no-dementia / controls | US$10,716 / $7,839 / $8,254 / $5,494 | same | same (all P<0.0001 vs VaD) | PMID 16155348 |
| annual direct cost, vascular dementia | US$5,112 (AD $4,625; FTD $4,924; between-group P>0.05) | Argentina, 104 patients, 2002–2008 | matched cost study | PMID 21044400 |
| hospitalization cost, VaD vs AD | significantly higher for VaD (P<0.001) | Argentina, same | post-hoc comparison | PMID 21044400 |
| societal cost, VaD vs AD | 23% higher for VaD (P=0.02) | rural Nordanstig cohort, Kungsholmen project, Sweden | Resource Utilization in Dementia instrument, societal perspective | PMID 16191249 |
| informal care, AD vs PD | 55.73 h/week and $17,492/y vs 15.8 h/week and $3,284/y; no data for other dementias | 21-study review | systematic review | PMID 23509789 |
The hospital-heavy, medication-light cost profile replicates from the US to Argentina, which argues it is a property of the disease's care pathway rather than of one payment system. No contemporary VaD-specific societal cost estimate exists.
Population attributable fractions (added 2026-09-02)¶
| Measure | Estimate (95% CI) | Population | Method | Source |
|---|---|---|---|---|
| dementia by age 80 attributable to ≥1 of hypertension, diabetes, smoking measured at 45–54 y | 21.8% (14.3–29.3) | ARIC, n=7,731, 33 y follow-up | population attributable fraction | PMID 40455489 |
| same, measured at 55–64 y | 26.4% (19.1–33.6) | ARIC, n=12,274 | same | PMID 40455489 |
| same, measured at 65–74 y | 44.0% (30.9–57.2) | ARIC, n=6,787 | same | PMID 40455489 |
| dementia occurring after age 80 attributable to those factors | 2–8% | ARIC | same | PMID 40455489 |
| combined PAF, 12 Lancet Commission modifiable factors | 45.4% (2011) → 52.5% (2018), change not significant | CHARLS, China, 75,214 person-waves | time-series PAF | PMID 38872868 |
| largest single contributor in China | low education, mean individual weighted PAF 11.3% | same | same | PMID 38872868 |
| midlife diabetes → 25-y incident dementia | HR 1.77 (1.53–2.04) | ARIC, 15,744 adults aged 44–66, 1,516 cases | Cox regression, fully adjusted | PMID 28783817 |
| midlife hypertension / prehypertension / smoking | HR 1.39 (1.22–1.59) / 1.31 (1.14–1.51) / 1.41 (1.23–1.61) | same | same | PMID 28783817 |
| APOE ε4 (reference comparison) | HR 1.98 (1.78–2.21) | same | same | PMID 28783817 |
Blood-pressure prevention, randomized (added 2026-09-02)¶
| Trial | Contrast achieved | Dementia result | Source |
|---|---|---|---|
| CRHCP cluster-randomized (33,995 adults, 326 villages, rural China, 48 months) | 22.0 mm Hg systolic (20.6–23.4); 9.3 mm Hg diastolic (8.7–10.0) | all-cause dementia RR 0.85 (0.76–0.95), P=0.0035; serious adverse events RR 0.94 (0.91–0.98) | PMID 40258956 |
| HYVET-COG (3,336 adults ≥80, mean 2.2 y, placebo-controlled) | 15 / 5.9 mm Hg | 38 vs 33 per 1,000 patient-years; HR 0.86 (0.67–1.09); pooled with other placebo trials HR 0.87 (0.76–1.00, P=0.045) | PMID 18614402 |
| Syst-Eur double-blind phase (2,418 adults ≥60, median 2.0 y) | 8.3 / 3.8 mm Hg | 7.7 → 3.8 per 1,000 patient-years (21 vs 11 events, P=0.05), 50% reduction | PMID 9802273 |
| Syst-Eur open extension (median 3.9 y) | — | 7.4 → 3.3 per 1,000 patient-years, 55%; HR 0.38 (0.23–0.64); 20 dementias prevented per 1,000 treated 5 years (7–33) | PMID 12374512 |
The dose–response across these four rows is the strongest argument that the pooled nulls reflect insufficient achieved contrast rather than absence of effect. None of the trials adjudicated vascular dementia separately.
Exercise and non-drug intervention in vascular cognitive impairment (added 2026-09-02)¶
| Intervention | Population | Result | Source |
|---|---|---|---|
| progressive aerobic training, 6 months thrice weekly vs usual care + education | 70 adults, mild subcortical ischaemic VCI, mean age 74 | ADAS-Cog −1.71 (−3.15 to −0.26, P=0.02); not sustained at 12 months (−0.63, −2.34 to 1.07); 6-min walk +30.35 m (5.82–54.86); diastolic BP −6.89 mm Hg (−12.52 to −1.26) | PMID 27760869 |
| progressive resistance training, 12 months vs balance-and-tone active control | 91 adults, SVD with MCI; 76 completed | ADAS-Cog-Plus −0.18 (−0.35 to −0.01, P=0.04); females −0.27 (−0.49 to −0.05, P=0.02), males null; CRP −2.93 (−5.36 to −0.49) | PMID 41795685 |
| citicoline 1 g/day for 12 months vs no citicoline (open label) | 347 first-ever ischaemic stroke, mean age 67.2 | attention–executive OR 1.721 (1.065–2.781) at 6 months, 2.379 (1.269–4.462) at 12 months; mRS ≤2 57.3% vs 48.7% (P=0.186) | PMID 23406981 |
| donepezil 24-week trial (study 307) | 603 NINDS-AIREN probable/possible VaD | ADAS-Cog effect size −1.90 (5 mg, P=0.001), −2.33 (10 mg, P<0.001); ADFACS −1.31 both doses (P=0.02); AE withdrawal 11.1/11.1/21.8% | PMID 12970516 |
The aerobic-exercise ADAS-Cog effect exceeds donepezil 5 mg (−0.92) and matches galantamine (−2.01) from the Cochrane pooling; no trial has compared them directly.
Behavioural and psychological symptoms by VCI subtype (added 2026-09-02)¶
| Subtype | Apathy | Depression | Irritability | Other |
|---|---|---|---|---|
| unspecified VCI | 54.29% | 43.48% | 38.76% | — |
| subcortical VCI | 62.01% | 52.11% | 44.73% | — |
| mixed dementia | 61.65% | 45.68% | — | sleep disturbance 44.63%; hallucinations 26.64% |
| VCI–no dementia | — | 44.97% | 32.75% | anxiety 30.07% |
Pooled from 35 NPI-based studies, n=5,805 (PMID 41043167). These figures conflict in direction with the registry-versus-clinic comparison of agitation recorded in the conflicts table below.
Criteria performance, additional (added 2026-09-02)¶
| Measure | Estimate (95% CI) | Population | Source |
|---|---|---|---|
| Mayo Clinic criteria (temporal link or bilateral infarction), pure VaD | sensitivity 0.75, specificity 0.81; LR+ 3.9 (2.2–6.7) | Rochester Epidemiology Project, 89 autopsies of 419 incident dementias | PMID 12707071 |
| pathological composition, same series | AD 51%, pure VaD 13%, AD+VaD 12%, other 24% | same | PMID 12707071 |
| interrater agreement, vascular dementia by ICD-10 | κ 0.79 (0.70–0.87) | meta-analysis, 22 studies of 7,577 screened | PMID 33942363 |
| interrater agreement, all-cause dementia by DSM-III-R | κ 0.66 (0.53–0.78) | same | PMID 33942363 |
| interrater agreement, Alzheimer disease by NINCDS-ADRDA | κ 0.71 (0.65–0.77) | same | PMID 33942363 |
| 2-year progression of clinic CIND to dementia | 34% overall; VCI-ND 40.0%, pre-AD 41.0% | Canadian Cohort Study of Cognitive Impairment, n=146 | PMID 16966831 |
| 2-year reversion of clinic CIND to normal | 14% overall; psychiatric CIND 20%, CIND-NOS 30% | same | PMID 16966831 |
| MCI prevalence by age (AAN guideline) | 6.7% (60–64), 8.4% (65–69), 10.1% (70–74), 14.8% (75–79), 25.2% (80–84) | systematic review | PMID 29282327 |
| 2-year cumulative dementia incidence in MCI >65 | 14.9% | same | PMID 29282327 |
Small-vessel disease markers, additional (added 2026-09-02)¶
| Measure | Estimate (95% CI) | Population | Source |
|---|---|---|---|
| multimarker SVD score ≥2 → incident all-cause dementia | HR 1.67 (1.05–2.66) adjusted for FSRP; 1.76 (1.10–2.81) adjusted for individual risk factors; Harrell c 0.82–0.83 | Framingham, 1,152 MRIs, median 7.4 y | PMID 40953349 |
| severe perivascular spaces in both regions → incident dementia over 8 y | OR 2.91 (1.43–5.95, P=0.003) | 414 community adults aged 72–92, 3T MRI | PMID 33504642 |
| DTI-ALPS → incident dementia in established SVD | HR 0.328 (0.183–0.588, P<0.001); PVS volume predicted nothing | 120 lacunar stroke with confluent WMH, 3 y imaging / 5 y cognition | PMID 38465597 |
| microinfarcts at autopsy | VaD 62%, AD 43%, mixed 33%, non-demented 24% | 32 neuropathological studies, 10,515 people | PMID 22234334 |
| WMH GWAS loci | 31 loci (21 novel) across WMH (n=42,310), FA (n=17,663), MD (n=17,467); 66 TWAS genes | UK Biobank and others | PMID 32358547 |
| cognitive reserve moderation | education and occupation predicted slower 3-y decline independently of WMH volume; education attenuated the WMH–7-y cognition relationship | LADIS, n=615 | PMID 27951523 |
Imaging measurement reliability (added 2026-09-02)¶
| Measure | Estimate | Population | Source |
|---|---|---|---|
| interrater κ, baseline visual WMH rating (Manolio, Fazekas–Schmidt, Scheltens) | 0.59–0.78; Fazekas–Schmidt better than Manolio (P=0.003) | 74 scans, 5 European centres, 3 raters | PMID 12574557 |
| interrater κ, WMH progression on follow-up scans | 0.19–0.39 | same | PMID 12574557 |
| agreement of visual scales with volumetry | Kendall W 0.37–0.57 (all P<0.001); between-scale Spearman 0.712–0.806 | 255 Austrian Stroke Prevention Study subjects | PMID 12574557 |
| MMSE + visual medial-temporal-atrophy rating | sensitivity 95% (AD), 85% (other dementias); specificity 96%; volumetry added nothing over MMSE | 143 memory-clinic patients | PMID 11032615 |
| lenticulostriate pulsatility index, hypertensive vs normotensive | higher PI and lower damping factor (both P=0.015); no difference in middle cerebral artery; unchanged by SVD-score adjustment | 28 hypertensive vs 25 matched controls, 7T phase-contrast | PMID 36722349 |
| grey-matter ASL spatial coefficient of variation | predicted 3-y memory decline, WMH progression, incident microbleeds and incident vascular events (29/368, 7.8%) | 368 memory-clinic patients | PMID 35871110 |
Post-stroke covert injury and delirium (added 2026-09-02)¶
| Measure | Estimate (95% CI) | Population | Source |
|---|---|---|---|
| new ischaemic lesions at 6 months after stroke | 15.5% of 503 patients; 72% DWI-positive, 91% clinically covert | prospective multicentre, 36-month follow-up | PMID 39417418 |
| those lesions → global cognition / mRS / recurrent stroke | β −0.31 (−0.48 to −0.14) / β 0.36 (0.14–0.58) / HR 3.81 (1.35–10.69) | same | PMID 39417418 |
| new brain infarct on 2-year MRI in anticoagulated AF | 5.5% (68/1,227); 85.3% clinically silent; 88.2% anticoagulated at baseline | Swiss-AF, mean age 71, 89.9% anticoagulated | PMID 35171989 |
| clinical stroke/TIA over the same 2 years | 2.3% (28/1,227) | same | PMID 35171989 |
| hospitalisation with delirium → 5-y dementia | HR 2.64 (1.47–4.74) with WMD; 3.41 (1.91–6.09) without WMD | OXVASC, 1,369 TIA/minor stroke, 209 dementias | PMID 38310893 |
| hospitalisation with infection → 5-y dementia | HR 1.75 (1.04–2.94) only in moderate/severe white-matter disease | same | PMID 38310893 |
| hospitalisation without delirium or infection | HR 1.01 (0.86–1.20) | same | PMID 38310893 |
| cumulative dementia after spontaneous ICH | 32.0–37.4% at 5 years | review of post-ICH cohorts | PMID 38640161 |
| dementia hazard by stroke subtype (5 y / 10 y) | ICH 2.14 / 1.61; TIA 1.92 / 1.61; ischaemic 1.81 / 1.49 | 8,236 Taiwanese stroke patients, 1:1 propensity-matched | PMID 31267646 |
Mechanism and biomarker quantities (added 2026-09-02)¶
| Measure | Estimate | Population | Source |
|---|---|---|---|
| plasma NfL, moderate-severe vs no SVD burden | 45.2 ± 16.0 vs 34.3 ± 15.1 pg/mL; OR 1.71 (1.24–2.35) | 496 non-demented ADNI participants | PMID 33517704 |
| rate of NfL change → SVD progression / WMH / lacunes | OR 1.38 (1.08–1.76) / 1.41 (1.10–1.79) / 1.99 (1.42–2.77) | same, 387 with longitudinal measures | PMID 33517704 |
| baseline plasma GFAP → SVD markers 9 years later | WMH β 0.06 (0.01–0.10); FA β 0.08 (0.03–0.13); MD β 0.14 (0.09–0.18); NfL null for all three | 5,270 UK Biobank adults aged 40–60 | PMID 41461058 |
| CAA prevalence in a population autopsy series | 44.1% with neocortical CAA | 211 Japanese-American men, HAAS | PMID 12058090 |
| CASI deficit, AD alone vs AD+CAA (vs non-demented no CAA) | 16.6% lower vs 45.9% lower | same, adjusted for plaques, tangles, infarcts, haemorrhage, APOE | PMID 12058090 |
| MCI prevalence in imaging-diagnosed CAA | 79% (27/34); executive z −1.14 ± 1.07, processing speed −1.06 ± 1.12, memory −0.44 ± 1.03 | prospective CAA cohort | PMID 27338926 |
| 4-year ICH risk by cortical superficial siderosis | 25% none / 28.9% focal / 74% (44.1–95.7) disseminated (log-rank P=0.0031) | 118 Boston-criteria CAA patients, median 24 months | PMID 24107862 |
| 6-month recurrent lobar ICH | 7% (21/292); disseminated siderosis HR 3.92 (1.38–11.17); acute cSAH on CT HR 3.48 (1.13–10.73) | 292 consecutive CAA-related lobar ICH survivors ≥55 | PMID 27694268 |
Neuropathology variance explained (added 2026-09-02)¶
| Measure | Estimate | Population | Source |
|---|---|---|---|
| variance in late-life cognitive decline explained by 5 pathologies together | 41% (tangles 34%, global AD 22%, Lewy bodies 8%, amyloid 6%, macroinfarcts 2%) | 856 ROS/MAP decedents, mean 7.5 annual evaluations | PMID 23798485 |
| variance explained by 11 pathologies together | 43%; AD indices 30–36%, non-AD neurodegenerative 4–10%, cerebrovascular 3–8% | 1,164 ROS/MAP decedents, up to 24 evaluations | PMID 33742668 |
| variance in onset of terminal decline / preterminal / terminal rates | 28% / 32% / 19% | same | PMID 33742668 |
| copathology frequency, Chinese community brain bank | LATE-NC 341 > ADNC 331 > PART 231 > CAA 183 > ARTAG 144 > α-synucleinopathy 124 > AGD 107 > hippocampal sclerosis 46, of 610 | National Human Brain Bank, China | PMID 39901730 |
| APOE ε4 allele frequency, same cohort | 13.63% | same | PMID 39901730 |
| sex difference in mixed pathology | women more likely to have AD + cerebrovascular pathology; men more likely pure Lewy body disease (adjusted for age, education, race, APOE ε4) | >1,500 community-dwelling decedents | PMID 31128096 |
Known conflicts and caveats¶
| Conflict | Interpretation |
|---|---|
| 7.4% vs 41.3% post-stroke dementia | first vs recurrent stroke and prior-dementia exclusions differ |
| 16.5% major NCD vs “about 10%” new dementia | criteria, timing, and hospital sampling differ |
| BP meta-analyses significant vs nonsignificant | endpoints, trial set, power, and methods differ |
| cognitive drug scales improve but ADL does not | statistical cognition change may lack clinical importance |
| CAA sensitivity varies 74.5–92.5% | cohort selection and sample size differ |
| autopsy percentages | cohort-specific, not global etiologic fractions |
| Syst-Eur 50–55% dementia reduction vs pooled OR 0.89–0.93 | small event counts (21 vs 11 blinded), a possible dihydropyridine-specific effect, and an untreated-hypertension population no longer recruitable; shown side by side, never averaged (PMID 9802273, 12374512, 34028812) |
| donepezil 5 mg MD −0.92 points vs SMD −1.11 | raw-scale versus standardized-mean-difference framing of overlapping trials; the SMD is a within-network ordering, not an effect magnitude (PMID 33704781, 35048806) |
| Western reviews find no recommendable drug vs 194-RCT Asian network ranking butylphthalide and huperzine A first | risk-of-bias inclusion thresholds and regional literature coverage differ; neither position has an independent cross-region replication (PMID 42635820, 39239652) |
| genetically determined WMH causal in two-sample MR (OR 1.43) vs null in individual-level analysis (HR 1.02) | different estimands from the same construct within one paper; unresolved (PMID 38776079) |
| clinical CADASIL prevalence ~2–11 per 100,000 vs genetic prevalence 1 in 277 | ascertainment plus genuinely low penetrance; the two numbers measure different things and must not be interchanged (PMID 15834040, 24840674, 40982447) |
| single vs mixed cerebrovascular pathology | single CVD pathologies showed no faster decline than none; only mixtures did. Present/absent coding of "cerebrovascular disease" averages across these groups (PMID 34601898) |
| probable-CAA category not associated with ICH recurrence while cortical superficial siderosis was | within one randomized trial's imaging subanalysis, on 13 events; category-level and marker-level risk are not interchangeable (PMID 41197104) |
| VaD incidence 1.4–1.5 per 1,000 py vs post-stroke dementia 7.4–41.3% | community incidence and post-event prevalence answer different questions and share no denominator |
| SVD imaging responds strongly to BP lowering (d −0.40) while dementia endpoints do not | either the imaging endpoint is not on the causal path to cognition, or the clinical endpoints are underpowered; unresolved (PMID 42614618, 34028812) |
| pooled Chinese VCI prevalence 1.54% no higher than national VaD prevalence 1.6% | a superset cannot be smaller than its subset; denominators (≥18 vs ≥60 y), criteria, and ascertainment differ. Shown side by side, never combined (PMID 40889799, 34178760, 33271079) |
| Hisayama VaD incidence 9.5 vs Rotterdam 1.5 and NEDICES 1.4 per 1,000 py | not explained by weaker ascertainment — Hisayama verified 91.2% morphologically. Candidate causes (stroke incidence, AD under-detection, environment) have never been decomposed (PMID 18977814, 9521184, 17727890) |
| VaD prevalence 1.8× higher in men at 60–69 vs sex-neutral cumulative incidence (0.04 both sexes) | prevalence and incidence diverge if male case fatality is higher; no study has reconciled them (PMID 31884487, 10599770) |
| probable-VaD autopsy sensitivity 0.20–0.25 vs 0.75 | conjunctive (NINDS-AIREN/ADDTC) versus disjunctive (Mayo) criteria architecture, in hospital versus population samples (PMID 11772694, 12707071) |
| interrater κ 0.30–0.61 across criteria vs κ 0.79 for ICD-10 vascular dementia | vignette/multi-criteria comparison versus pooled routine practice; ICD-10's high κ may reflect a definition almost nobody meets (PMID 10681076, 33942363) |
| perivascular spaces: OR 2.91 for 8-year dementia vs no cross-sectional association vs no effect of PVS volume | counted extremes over long horizons, population-average burden cross-sectionally, and segmented volume in severe disease are three different measurements (PMID 33504642, 30068634, 38465597) |
| CAA has no independent dementia effect (OR 0.96 after Braak adjustment) vs CASI 45.9% lower in AD+CAA than 16.6% in AD alone | mediation framing versus interaction framing of a conditional effect; both analyses are correct and answer different questions (PMID 39481068, 12058090) |
| vascular dementia is the agitated dementia vs the apathetic dementia | long-term-care registry (n=10,405) versus memory clinic (n=180); setting and rating instrument differ, and no study has tested that explanation (PMID 35491774, 28245482) |
| Alzheimer caregiving is more burdensome vs vascular caregiving is more burdensome | reverses with severity: vascular greater at mild-to-moderate, Alzheimer greater at severe (PMID 25475248, 10097779) |
| cerebrovascular pathology explains 3–8% of cognitive-decline variance in the cited cohorts and models | prevalence times effect, not effect alone, determines population impact; this descriptive variance estimate is not a causal treatment-effect ceiling (PMID 33742668) |
| aerobic exercise ADAS-Cog −1.71 vs donepezil 5 mg −0.92 | different trial sets, no head-to-head comparison exists; the exercise effect did not persist 6 months after stopping (PMID 27760869, 33704781) |
| 2026-08-31 registry sweep found no phase-3 successor to LACI-2; 2026-09-02 sweep found one | registry absence claims decay within days; IMPACT (NCT07252544, n=3,156) was registered but not returned by the earlier query |