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Showing 51 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. Stand-alone plasma p-tau217 gave 81% accuracy and 79% PPV; confirming positives with PET or CSF raised both to 91% while cutting PET scans needed to find 100 amyloid-positive people from 536 to 124. Immunoassays matched mass spectrometry on PPV but had lower accuracy. |
Accuracy and positive predictive value for amyloid positivity (CSF or PET) in cognitively unimpaired people, stand-alone and in a two-step workflow | cross-sectional study | 2,916 | As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124 |
JAMA Neurology
2025 ✓ Peer-reviewed PMID 40952756 |
| 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. All four assays (Lumipulse, Johnson & Johnson, ALZpath, NULISA) gave statistically equivalent AUCs of 0.84-0.90 for amyloid positivity, with cross-platform correlations of 0.40-0.86. |
Cross-assay agreement and AUC for amyloid PET positivity across four p-tau217 immunoassays | cross-sectional study | 344 | All four p-tau217 assays exhibited moderate to strong cross-platform correlations (Spearman correlations of 0.40–0.86), and statistically equivalent AUCs (of 0.84–0.90) for determining Aβ positivity |
Alzheimer's Research & Therapy
2026 ✓ Peer-reviewed PMID 41652516 |
| 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. Subgroup-specific optimal cutoffs and a double-cutoff strategy both improved accuracy over the standard single cutoff, most markedly in chronic kidney disease (0.65 to 0.83) and anaemia. |
Accuracy of plasma p-tau217 for amyloid PET positivity under standard, subgroup-optimal and double cutoffs in people with kidney disease, abnormal BMI or anaemia | cross-sectional study | 2,571 | In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort |
JAMA neurology
2026 ✓ Peer-reviewed PMID 41627837 |
| 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 prespecified APS2 cut point gave 91% accuracy, 90% sensitivity and 92% specificity against amyloid PET. |
Agreement with amyloid PET in an independent cohort (ADNI) | cross-sectional study | 191 | Concordance with amyloid PET was high (AUC-ROC 0.95 (95% CI): 0.93-0.98); 54% of participants had a positive APS2. The previously validated APS2 cut point yielded an overall accuracy of 91% (95% CI: 86-94%), sensitivity 90% (95% CI: 83-94%) and specificity 92% (95% CI: 84-96%) |
npj Dementia
2025 ✓ Peer-reviewed PMID 40917102 |
| 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 detected amyloid PET positivity with 82% sensitivity and 86% specificity, comparable to CSF p-tau217; less sensitive for tau PET. |
Sensitivity and specificity for amyloid and tau PET positivity (pooled) | meta-analysis | not stated | Plasma p-tau217 showed 82% sensitivity for detecting amyloid and 83% for tau, with 86% and 83% specificity, respectively. CSF p-tau217 had 79% sensitivity for amyloid and 91% for tau, with 91% and 84% specificity |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 39711334 |
| 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. AUC 0.93-0.96; accuracy 89-91% in secondary care and 85% in primary care, lower (83%) at age 80 or older; a two-cutoff approach raised accuracy to 92-94% at the cost of 12-17% intermediate results. |
Diagnostic accuracy for Alzheimer pathology (CSF-defined) in secondary and primary care | cross-sectional study | 1,767 | Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93-0.96. In secondary care, the accuracies were 89-91%, the positive predictive values 89-95% and the negative predictive values 77-90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%) |
Nature Medicine
2025 ✓ Peer-reviewed PMID 40205199 |
| 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 was the best-performing marker (88.1% sensitivity, 88.7% specificity, AUROC 91.1%, moderate certainty), ahead of p-tau181 and p-tau231; about 90% of studies were at high risk of bias. |
Pooled sensitivity, specificity and AUROC for biologically defined Alzheimer's disease | meta-analysis | 29,625 | Plasma p-tau217 was the highest-performing biomarker for identifying biologically defined Alzheimer's disease, with pooled sensitivity of 88·1% (95% CI 86·7-89·5, moderate certainty of evidence), specificity of 88·7% (87·4-89·9, moderate certainty of evidence), area under the receiver operating characteristic curve (AUROC) of 91·1% (88·9-92·4, moderate certainty of evidence), and diagnostic odds ratio of 50·7 (40·6-63·4). p-tau181 pooled sensitivity was 80·5% (78·4-82·4, low certainty of evidence), specificity was 76·4% (74·1-78·6, low certainty of evidence), AUROC was 81·5% (80·2-82·9, low certainty of evidence) |
The Lancet Neurology
2025 ✓ Peer-reviewed PMID 40818474 |
| 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 Pitt-p-tau217 assay separated PSEN1 carriers from controls (AUC 0.94) and amyloid PET-positive from -negative cognitively normal adults (AUC up to 0.84), equivalent to the ALZpath assay. |
Classification accuracy of a new p-tau217 assay against PSEN1 carrier status and amyloid PET | cross-sectional study | 363 | Pitt-p-tau217 differentiated neuropathologically confirmed PSEN1 mutation carriers from controls with area under the curve (AUC) = 0.94, and amyloid beta (Aβ) positron emission tomography (PET)-positive from Aβ PET-negative cognitively normal older adults with AUC up to 0.84, equivalent to ALZpath-p-tau217 results. Both Pitt-p-tau217 and ALZpath-p-tau217 were slightly elevated in tau PET-positive versus tau PET-negative participants. Between-assay correlations were up to 0.93 |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40665482 |
| 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 Lumipulse plasma p-tau217/Aβ42 ratio reached AUC 0.963-0.966 for amyloid PET and 0.947-0.974 for tau PET, equivalent to CSF tests and better than plasma p-tau217 alone, with fewer intermediate results. |
Diagnostic accuracy for abnormal amyloid PET and tau PET in a clinic and a community cohort | cross-sectional study | 512 | Plasma p-tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974) ... The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40156286 |
| 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/Aβ42 had the highest accuracy (0.88 in Black and 0.91 in White participants) and fewest intermediate results, with no difference in classification by race. |
Accuracy for amyloid PET positivity in people who self-identify as Black or White | cross-sectional study | 1,135 | In the test set, plasma p-tau217/Aβ42 had the highest accuracy (pBlack: 0.88, pWhite: 0.91) and lowest proportion of intermediate classifications (≤0.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33) |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40801297 |
| 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 symptomatic AD with 95% sensitivity and 82% specificity (86% with the Aβ42 ratio) and tracked CSF biomarkers closely (AUC 0.94-0.96); reduced kidney function raised levels in patients without AD. |
Sensitivity and specificity for symptomatic AD, and agreement with CSF biomarkers, in a tertiary outpatient memory clinic | cross-sectional study | 509 | Plasma p-tau217 distinguished patients with diagnoses of symptomatic AD with 95% sensitivity and 82% specificity. Integration of Aβ42 measurements (p-tau217/Aβ42) incrementally improved specificity (86%). Plasma p-tau217 and p-tau217/Aβ42 concentrations closely associated with established CSF biomarkers of AD (area under the curve [AUC]: 0.94 and 0.96, respectively) |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 40476540 |
| 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 APS2 blood test reached AUC 0.96-0.97 and 88-92% accuracy, and its 91% accuracy for clinical AD beat primary care physicians (61%) and dementia specialists (73%). |
Diagnostic accuracy for Alzheimer pathology (CSF-defined), and for clinical AD versus physicians' assessment | cross-sectional study | 1,213 | the AUC was 0.97 (95% CI, 0.95-0.99) when the APS2 was used, the PPV was 91% (95% CI, 87%-96%), and the NPV was 92% (95% CI, 87%-96%) [primary care, single batch]; Primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) for identifying clinical AD after clinical examination, cognitive testing, and a computed tomographic scan vs 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) vs 91% (95% CI, 88%-95%) using the APS2 |
JAMA
2024 ✓ Peer-reviewed PMID 39068545 |
| 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. APS2 gave AUC 0.94 and 88% agreement with amyloid PET, with similar performance by ethnicity, sex, age and APOE4 status. |
Agreement with amyloid PET (brain amyloidosis) | cross-sectional study | 583 | The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET |
Alzheimer's & Dementia
2024 ✓ Peer-reviewed PMID 38491912 |
| 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. Plasma Aβ42/40, p-tau217, p-tau181 and NfL classified AD with AUC 83% and FTLD with 88%, consistent across countries, rising to 89% and 95% when combined with neuroimaging patterns and cognitive measures. |
Discrimination of AD and frontotemporal lobar degeneration from controls by plasma AT(N) biomarkers in a multinational Latin American cohort | cross-sectional study | 605 | Classification models achieved receiver operating characteristic areas under the curve (ROC AUCs) of 83% for AD and 88% for FTLD ... Biomarker alterations combined with disease-specific neuroimaging patterns and cognitive measures further improved accuracy (ROC AUCs of 89% for AD and 95% for FTLD) |
Nature Aging
2026 ✓ Peer-reviewed PMID 41688826 |
| 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 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyBenefit was larger for younger, male and non-spousal carers. The largest single effect (training the person with dementia) rests on 10 observations and the authors call it promising rather than definitive. |
Carer anxiety and depression | meta-analysis | not stated | "Interventions generally showed a significant reduction in anxiety and depression with varied effects on SWB [subjective well-being]" across 175 studies and 342 intervention treatments |
Dementia and Geriatric Cognitive Disorders
2026 ✓ Peer-reviewed PMID 40550226 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyA pilot designed to test feasibility; 68 carers and a 2-week outcome. |
Pre-death grief at 2 weeks | randomised trial | 68 | Pre-death grief Cohen d = -0.38 (mean change -3.29, SD 8.64, p=0.03) at 2 weeks |
JAMA Network Open
2026 ✓ Peer-reviewed PMID 42018322 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyDigital psychological interventions reduced caregiver burden and improved self-efficacy and quality of life; the effect on depressive symptoms was not statistically significant (P = .06). |
Caregiver burden (primary); depression, self-efficacy and quality of life | meta-analysis | 750 | digital psychological interventions significantly reduced caregiver burden [Standardized mean difference (SMD) = -0.21, 95% CI: -0.35 to -0.07; P = .003] and improved self-efficacy (SMD = 0.38, 95% CI: 0.15 to 0.61, P = .001) and quality of life (SMD = 0.59, 95% CI: 0.27 to 0.91, P < .001). But digital psychological interventions have no statistically significant in alleviating depressive symptoms (P = .06) |
Age and ageing
2026 ✓ Peer-reviewed PMID 41505195 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyAt the 1-month comparison the automated self-guided programme reduced depression and burden and increased positive gains versus waitlist; anxiety did not differ. Group differences mostly disappeared once controls received the programme. |
Caregiver depression (PHQ-9) at 1 month versus waitlist (primary); anxiety, burden and positive gains | randomised trial | 274 | At 1-month follow-up, coinciding with exclusive access to PDC30, intervention caregivers showed significant improvements in depression (d = -0.37), burden (d = -0.34), and positive gains (d = 0.42) |
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
2026 ✓ Peer-reviewed PMID 41644333 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyA factorial trial of components: the mindfulness component carried the benefit and amplified the others. |
Carer depressive symptoms (PHQ-9) at 12 months | randomised trial | 250 | Mindfulness component: PHQ-9 depressive symptoms β = -2.13 (95% CI -2.85 to -1.38) at 12 months |
JAMA Network Open
2025 ✓ Peer-reviewed PMID 40094667 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyDirection is for NIDUS-Family: an 89% probability of cost-effectiveness from a health and social care perspective (87% societal) and £8,934 (37%) lower average costs, though the cost difference's confidence interval includes zero. |
Probability of cost-effectiveness at £20,000-30,000 per QALY and 12-month costs versus goal setting and routine care | randomised trial | 302 | At both a £20 000 and £30 000 decision threshold, there was an 89% probability that NIDUS-Family was cost-effective compared with usual care from a health and social care perspective, and an 87% probability from a societal perspective. Intervention participants accrued on average £8934 (37%) less in costs than control participants (95% CI -£59 460 to £41 592) |
The Lancet Healthy Longevity
2025 ✓ Peer-reviewed PMID 39978389 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyThe outcome is how prepared carers felt to decide about firearm access, not whether any injury was avoided. |
Preparation for Decision Making score | randomised trial | 500 | Preparation for Decision Making score +4.80 points (95% CI 0.53 to 9.07) vs control |
Annals of Internal Medicine
2024 ✓ Peer-reviewed PMID 39531391 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyDirection is for psychosocial and pharmacological interventions, which the review reports as showing mild to modest efficacy in high-quality meta-analyses. A narrative clinical review summarising other meta-analyses, not a new pooled estimate. |
Caregiver burden | None | not stated | Psychosocial interventions include support groups or psychoeducational interventions for caregivers of dementia patients (effect size, 0.09-0.23). Pharmacologic interventions include use of anticholinergics or antipsychotic medications for dementia or dementia-related behaviors in the care recipient (effect size, 0.18-0.27) |
JAMA
2014 ✓ Peer-reviewed PMID 24618967 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment |
Benefit
whyBenefit in Hispanic and White caregivers and in Black spousal caregivers; not in Black non-spousal caregivers. |
Caregiver quality of life and depression at 6 months | randomised trial | 642 | Depression: 12.6% (intervention) vs. 22.7% (control) at 6 months |
Annals of Internal Medicine
2006 ✓ Peer-reviewed PMID 17116917 |
| Carer psychosocial / skills intervention Care, carers and services | Treatment | Benefit | Time to nursing home placement | randomised trial | 406 | HR 0.717 for nursing home placement; median time to placement 557 days longer (model-predicted) in the intervention group |
Neurology
2006 ✓ Peer-reviewed PMID 17101889 |
| Cognitive screening instrument accuracy Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Tablet tests correlated strongly with MMSE, MoCA and Trails A (r > 0.7) and the Match test separated amyloid-positive from -negative patients (AUC 0.82) better than MMSE or MoCA (0.75). |
Correlation with pen-and-paper tests and discrimination of amyloid-positive from amyloid-negative early-onset AD patients | cross-sectional study | 475 | Match and Flanker were associated with all pen‐and‐paper tests, with strongest correlations observed with the MMSE, MoCA, and Trails A (r's >0.7) ... Of TabCAT tests, Match best discriminated Aβ+ from Aβ‐ patients (Area Under the Curve (AUC)=0.82), outperforming the MMSE (AUC=0.75) and MoCA (AUC=0.75), and comparable to the overall best performing test Benson Figure Recall (AUC=0.85 |
Alzheimer's & Dementia (AAIC 2025 conference abstract)
2025 ⚠ Conference abstract — not peer-reviewed DOI 10.1002/alz70857_104654 |
| Cognitive screening instrument accuracy Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Pooled sensitivity 76% and specificity 83% for dementia, with 73% / 84% in primary care; the authors call it a practical screening tool while noting high or unclear risk of bias in patient selection and timing. |
Pooled sensitivity and specificity of the Mini-Cog for dementia, MCI and cognitive impairment | meta-analysis | not stated | To detect dementia (six studies, n = 4772), the Mini-Cog showed 76% sensitivity and 83% specificity. To detect MCI (two studies, n = 270), it showed 84% sensitivity and 79% specificity. To detect CI (eight studies, n = 2152), it had 67% sensitivity and 83% specificity. In the primary care setting, to detect either MCI, dementia, or CI (eight studies, n = 5620), the Mini-Cog demonstrated 73% sensitivity and 84% specificity |
PLOS ONE
2024 ✓ Peer-reviewed PMID 38483857 |
| Cognitive screening instrument accuracy 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-stage GPCOG had sensitivity 0.85 and specificity 0.86 against DSM-IV dementia, and was superior to the Abbreviated Mental Test. |
Sensitivity, specificity and positive predictive value of the GPCOG for dementia in general practice | cross-sectional study | 283 | The two-stage method of administering the GPCOG (cognitive testing followed by informant questions if necessary)had a sensitivity of 0.85, a specificity of 0.86, a misclassification rate of 14%, and positive predictive value of 71.4% |
Journal of the American Geriatrics Society
2002 ✓ Peer-reviewed PMID 11943052 |
| Cost-effectiveness of multidomain prevention programme Care, carers and services | Prevention |
Benefit
whyDirection is for value for money: the intervention was modelled as dominant, saving JPY 452,826 per person and adding 0.08 QALYs over 35 years, with sensitivity analyses described as confirming robustness. A model extrapolating an 18-month trial. |
Lifetime costs and QALYs of the J-MINT multidomain intervention versus usual care (35-year model) | modelling study | not stated | Over 35 years, J-MINT was projected to achieve cost savings of JPY 452,826 per person and a gain of 0.08 QALYs |
The journal of prevention of Alzheimer's disease
2026 ✓ Peer-reviewed PMID 41478834 |
| Dementia care management / navigation Care, carers and services | Treatment |
Benefit
whyThe community health worker programme achieved verified linkage to medical care in 16.7% of dyads versus none in the control arm. Caregiver outcomes were largely unchanged, with self-efficacy favouring control. |
Clinic-verified linkage to medical services at 6 months (primary); caregiver psychosocial outcomes | randomised trial | 287 | PLAN increased linkage to medical services versus control (16.7% vs 0%, chi-squared [df = 1] = 24.05, p < 0.001). Caregiver outcomes were largely unchanged, with self-efficacy favoring control |
Alzheimer's & dementia : the journal of the Alzheimer's Association
2026 ✓ Peer-reviewed PMID 42233272 |
| Dementia care management / navigation Care, carers and services | Treatment |
Benefit
whyDirection is for the extended nursing role intervention: 74% fewer unmet needs and higher quality of life at six months, with a small QALY gain at about 1,425 EUR added cost; no effect on caregiver burden. |
Unmet needs, quality of life, caregiver burden and cost per QALY at six months (advanced dementia care management by nurses in extended roles) | randomised trial | 417 | PlwD receiving the intervention had 74% lower unmet needs (0.26, CI95%: 0.17 to 0.40, p < 0.001) and higher quality of life (0.04, CI95%: 0.01 to 0.07, p = 0.017) than controls. There was a gain in quality-adjusted life years (0.01, CI95%: -0.001 to 0.018) at slightly higher costs (1,425 EUR, CI95%: 638 to 2,211) |
Alzheimer's & Dementia
2025 ✓ Peer-reviewed PMID 41143334 |
| 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 |
| Dementia care management / navigation Care, carers and services | Treatment |
Benefit
whyDirection is for collaborative dementia care management: fewer neuropsychiatric symptoms, lower caregiver burden, better mental health and 0.137 QALYs gained at no significant added cost (3186€ per QALY) over 36 months; no difference in antidementia drug use, overall quality of life or inappropriate medication. |
Neuropsychiatric symptoms, caregiver burden, quality of life and cost per QALY at 36 months after 6 months of collaborative dementia care management | randomised trial | 428 | Participants receiving CDCM showed significantly fewer behavioral and psychological symptoms (adjusted mean difference [AMD] in NPI score, -10.26 [95% CI, -16.95 to -3.58]; P = .003; Cohen d, -0.78 [95% CI, -1.09 to -0.46]) ... and lower caregiver burden (AMD in BIZA-D score, -0.59 [95% CI, -0.81 to -0.37]; P < .001; Cohen d, -0.71 [95% CI, -1.03 to -0.40]) ... The CDCM group gained QALYs (0.137 [95% CI, 0.000 to 0.274]; P = .049; Cohen d, 0.20 [95% CI, -0.09 to 0.40]) but had no significant increase in costs (437€ [-5438€ to 6313€] [US $476 (95% CI, -$5927 to $6881)]; P = .87; Cohen d, 0.07 [95% CI, -0.14 to 0.28]), resulting in a cost-effectiveness ratio of 3186€ (US $3472) per QALY |
JAMA Network Open
2024 ✓ Peer-reviewed PMID 38967926 |
| Dementia screening / case finding Care, carers and services | Treatment |
Benefit
whyThe outcome is how many diagnoses were made, not whether anyone was better off. The passive digital marker alone did not raise detection (AOR 0.84, 95% CI 0.63-1.11). |
New dementia diagnosis within 12 months | randomised trial | 5,325 | Adjusted OR for new dementia diagnosis 1.31 (95% CI 1.05-1.64) with QDRS plus passive digital marker vs usual care |
JAMA Network Open
2025 ✓ Peer-reviewed PMID 41212562 |
| Health-system and payment model Care, carers and services | Treatment |
Benefit
whyDirection is for the benefit redesign: projected out-of-pocket drug spending fell 55% ($56 to $25) for low-income-subsidy beneficiaries and 25% ($772 to $576) for others, with larger reductions for people with 6-8 comorbidities. |
Simulated annual out-of-pocket drug spending for Medicare beneficiaries with dementia under the 2025 Part D cost-sharing rules | modelling study | 1,677 | we project average annual OOP drug expenditures among LIS beneficiaries with dementia to decrease from $56 to $25-representing a $31, or 55%, reduction. In contrast, among non-LIS beneficiaries, average OOP drug expenditures is projected to decrease from $772 to $576, a $196, or 25% reduction |
Value in Health
2025 ✓ Peer-reviewed PMID 39880200 |
| 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 |
| Plasma proteomics diagnostic model (ProtAIDe-Dx) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Cross-validated balanced accuracy of 70-95% and AUC above 78% across the six conditions; the model is a development-stage tool with one external memory-clinic validation sample. |
Classification accuracy for six dementia-associated conditions from plasma proteomics | cross-sectional study | 17,187 | ProtAIDe-Dx achieves cross-validated balanced classification accuracy of 70-95% and area under the curve of >78% across all conditions |
Nature medicine
2026 ✓ Peer-reviewed PMID 41917159 |
| Safety / firearm decision aid Care, carers and services | Treatment |
Benefit
whyThe outcome is how prepared carers felt to decide about firearm access, not whether any injury was avoided. |
Preparation for Decision Making score | randomised trial | 500 | Preparation for Decision Making score +4.80 points (95% CI 0.53 to 9.07) vs control |
Annals of Internal Medicine
2024 ✓ Peer-reviewed PMID 39531391 |
| Sleep intervention for carers/dyads Care, carers and services | Treatment |
Benefit
whyDirection is for DREAMS START against treatment as usual: a 78% probability of being cost-effective at £20,000 per QALY, with cost and QALY differences individually non-significant. The clinical sleep result is in the table under its own row. |
Cost per QALY gained (within-trial cost-utility) | randomised trial | 377 | The mean incremental difference in QALYs per person with dementia was 0·016 more (95% CI 0·000 to 0·033) for the intervention group than for the TAU group, indicating no significant difference in quality of life. At a £20 000 per QALY gained decision threshold, there was a 78% probability that DREAMS START is cost-effective, compared with TAU |
The Lancet Healthy Longevity
2025 ✓ Peer-reviewed PMID 40412418 |
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