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Every row of the evidence table
One row per finding: what was tested, which way the result went, and how the study was built. The answer by area, and where the studies disagree, are on the main page.
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Showing 14 of 382 rows. One row per study per exposure: a study that tested two different things appears twice, once for each.
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| Exposure | Question | Direction | Outcome measured | Design | People | Effect size, as the source reported it | Source |
|---|---|---|---|---|---|---|---|
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Prevention |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The estimated age at plasma %p-tau217 positivity predicted age at symptom onset (adjusted R2 0.337-0.612) with a median absolute error of 3.0-3.7 years, which the authors call acceptable for trials but not yet for individual clinical use. |
Predicted age at onset of Alzheimer's symptoms from plasma %p-tau217 clock models | cohort study | 603 | The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R2 of 0.337-0.612) with a median absolute error of 3.0-3.7 years |
Nature medicine
2026 ✓ Peer-reviewed PMID 41714746 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Prevention |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Combined plasma %p-tau217 and Aβ42/40 detected abnormal CSF amyloid status (AUC 0.949) and each predicted rising amyloid PET over time in people who started below the positivity threshold, replicated in two further cohorts; p-tau231 and GFAP added no clear independent value. |
Prediction of subsequent brain amyloid accumulation (PET/CSF) in cognitively unimpaired people with subthreshold amyloid | cohort study | 983 | a combination of plasma %p-tau217 and Aβ42/40 showed better performance (area under the curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers ... longitudinal Aβ-PET (%p-tau217: β = 0.67; 95% CI, 0.48-0.87; Aβ42/40: β = -0.33; 95% CI, -0.51 to -0.15; %p-tau217 × Aβ42/40: β = -0.31; 95% CI, -0.44 to -0.18; P < .001) |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 39068669 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Among p-tau217-positive patients, a positive eMTBR-tau243 identified clinically established Alzheimer's disease with 81% accuracy and predicted faster cognitive decline and tau accumulation. |
Classification of established Alzheimer's disease by plasma eMTBR-tau243 among %p-tau217-positive patients | cohort study | 572 | 194 (55%) of 350 %p-tau217-positive patients were also positive for eMTBR-tau243, with an accuracy of 81% (95% CI 76-84), PPV 84% (95% CI 78-88), negative predictive value (NPV) 77% (95% CI 68-82), and sensitivity 82% (95% CI 76-87) for established Alzheimer's disease, in cross-sectional analyses |
The Lancet. Neurology
2026 ✓ Peer-reviewed PMID 41864233 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. All p-tau217 tests detected abnormal amyloid PET (AUC 0.91-0.96) and tau PET (0.94-0.97); the mass-spectrometry %p-tau217 ratio was best (accuracy 0.93 versus 0.83-0.88 for immunoassays) and is proposed as a stand-alone confirmatory test, with immunoassays better suited to triage. |
Accuracy of five plasma p-tau217 tests for amyloid PET and tau PET status, benchmarked against CSF tests | cohort study | 998 | All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET [area under the curve (AUC) range: 0.91-0.96] and tau-PET (AUC range: 0.94-0.97) ... For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 0.91 (immunoassays: 0.84-0.87) and a specificity of 0.94 (immunoassays: 0.85-0.89) |
Brain
2025 ✓ Peer-reviewed PMID 39468767 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The ALZpath plasma p-tau217 immunoassay reached AUC 0.92-0.96 for amyloid and 0.93-0.97 for tau across three cohorts, comparable with CSF, and a three-range cut-off cut confirmatory testing by about 80%. |
Accuracy for abnormal amyloid and tau pathology (PET or CSF) and longitudinal change | cohort study | 786 | High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80% |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 38252443 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 identified amyloid positivity with AUC 0.94; a two-cut-point rule sent only 17% for CSF or PET (sensitivity 0.94, specificity 0.86), and among amyloid-positive people it identified high tau load (AUC 0.92), potentially avoiding 56.9% of tau-PET scans. |
Identification of amyloid positivity and of high tau-PET load (to select candidates for anti-amyloid antibodies) | cohort study | 912 | plasma p-tau217 was most strongly associated with Aβ positivity (test-set area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI, 0.90-0.97) ... This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95) ... At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aβ-positive participants |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 38048096 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. A blood model of p-tau217, age and APOE ε4 (AUC 89.3% development, 94.3% validation) used to triage patients gave 88-92% overall accuracy while cutting confirmatory CSF tests by 61-86%. |
Accuracy for amyloid PET status and reduction in confirmatory CSF tests with a two-step plasma p-tau217 workflow | cohort study | 348 | Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively |
Nature Aging
2023 ✓ Peer-reviewed PMID 37653254 |
| Blood biomarkers (GFAP, NfL, p-tau181) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for disclosing the blood panel during multidisciplinary meetings: median diagnostic confidence rose from 80% to 90%, though the suspected etiology changed in only 5% of patients and the syndrome diagnosis in 1%. Against CSF/PET, high- and low-probability results identified 76% of amyloid positives and 85% of negatives. |
Change in clinician diagnostic confidence and in syndrome or etiological diagnosis after disclosure of a plasma biomarker panel (p-tau181, GFAP, NfL) | cohort study | 450 | Median (IQR) diagnostic confidence in the total cohort increased from 80% (70%-90%) to 90% (70%-90%) after BBM disclosure (P < .001), increasing in 207 patients (46%), unchanged in 175 patients (39%), and decreasing in 68 patients (15%). Following BBM disclosure, syndrome diagnoses were revised in 6 patients (1%) and primary etiology was revealed in 23 patients (5%) |
JAMA Network Open
2026 ✓ Peer-reviewed PMID 42593792 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Prevention |
Benefit
whyDirection is for the blood test's prognostic performance: plasma p-tau217 predicted cognitive decline and progression to MCI as well as tau PET (R2 0.33 vs 0.34; HR 1.57 vs 1.61), and using the blood test first cut the number needed to screen for a trial by 94%. A prognostic-performance result, not a health outcome. |
Prediction of future cognitive decline and progression to MCI: plasma p-tau217 head-to-head with tau PET | cohort study | 1,474 | plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48-1.76) versus HRplasma = 1.57 (1.43-1.72), Pdifference = 0.322) ... Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone |
Nature Aging
2025 ✓ Peer-reviewed PMID 40155777 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The two-marker plasma model matched PET-based stages with a C index of 0.91 in both the derivation and validation cohorts, tracked clinical stage (C index 0.84-0.86) and aligned with autopsy ADNC (AUC 0.96), improving on %p-tau217 alone at the intermediate stage. |
Concordance of a plasma %p-tau217 plus eMTBR-tau243 staging model with amyloid/tau PET-based biological stages, clinical stage and autopsy-confirmed AD pathology | cohort study | 1,028 | A plasma-based model with %p-tau217 and eMTBR-tau243 was derived, which demonstrated high concordance with established PET-based stages (C index, 0.91; 95% CI, 0.90-0.92) and was associated with clinical stage within the AD continuum (C index, 0.84; 95% CI, 0.82-0.86). In the validation cohort, concordance with PET-based stages was high (C index, 0.91; 95% CI, 0.87-0.94), as was concordance with clinical stage (C index, 0.86; 95% CI, 0.82-0.89) ... In the neuropathology subsample, plasma staging was strongly aligned with autopsy-confirmed AD pathology using the Alzheimer Disease Neuropathologic Change scale (area under the curve, 0.96; 95% CI, 0.91-1.00) |
JAMA Neurology
2026 ✓ Peer-reviewed PMID 42189519 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Serum GFAP tracked post-mortem tau pathology independently of amyloid, correlated negatively with brain weight and cognition, correlated with astrocyte reactivity in tissue, and separated neuropathologically confirmed AD from non-AD dementias with AUC 0.91. |
Correlation of serum GFAP with post-mortem tau pathology, brain weight and astrocyte reactivity, and discrimination of autopsy-confirmed AD from non-AD dementia | cohort study | 139 | an association between serum GFAP level and post-mortem tau pathology (β = 12.85; P < 0.001) that was independent of amyloid deposits (β = 13.23; P = 0.02) ... a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = -0.35; P < 0.001) ... its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer's disease dementias from non-Alzheimer's disease dementias |
Brain
2024 ✓ Peer-reviewed PMID 38634687 |
| CSF alpha-synuclein seed amplification assay Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Smell testing followed by CSF seed amplification only in those with reduced smell predicted brain Lewy body pathology with 94% accuracy and cut CSF testing by 43%; in a living cohort it predicted CSF assay status with 79% accuracy. |
Accuracy for autopsy-confirmed Lewy body pathology and reduction in confirmatory CSF testing | cohort study | 1,567 | Among 358 autopsied participants, the two-step workflow predicted brain LBP with high accuracy overall (94%), and within clinical subgroups (clinical parkinsonism=95%; clinical Alzheimer's disease [AD]=94%; clinically unimpaired [CU]=93%). It reduced the need for confirmatory CSF testing by 43% overall (23% clinical parkinsonism; 35% clinical AD; 80% CU). In an independent in vivo cohort (N=1209), the workflow predicted CSF α-syn SAA status with 79% accuracy and reduced CSF testing by 26% |
Nature Communications
2025 ✓ Peer-reviewed PMID 40764485 |
| Dementia care management / navigation Care, carers and services | Treatment |
Benefit
whyDirection is for the Care Ecosystem programme: total cost of care was $475.80 per member per month lower than matched controls at 12 months, with fewer emergency, outpatient and professional visits. |
Total cost of care per member per month at 12 months versus propensity-matched controls | cohort study | 242 | Care Ecosystem participants had significantly lower total cost of care at 12 months, mean savings of $475.80 per member per month compared with controls |
American Journal of Managed Care
2024 ✓ Peer-reviewed PMID 39146484 |
| Naturalistic driving behaviour (digital marker of MCI) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Driving features distinguished drivers with MCI from those with normal cognition (AUC 0.82), rising to 0.87 with demographics, APOE4 and cognition; drivers with MCI showed greater declines in trip frequency, night driving and route variety. |
Discrimination of MCI from normal cognition by daily driving features, and longitudinal change in driving | cohort study | 298 | Key features such as medium trip distance, speeding events, entropy, and maximum distance distinguished drivers with MCI from those with NC (area under the curve [AUC] 0.82, 95% CI 0.75-0.89). Adding demographics, APOE ε4, and cognitive composite improved AUC to 0.87 (95% CI 0.81-0.93) |
Neurology
2025 ✓ Peer-reviewed PMID 41296993 |