Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Highest usefulness score first. Studies without a score come last.
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Synthesis methods We meta-analysed results for each outcome within each comparison using the inverse variance method and the random-effects model.
Why it matters
This Cochrane review of 17 studies with 20,342 participants found that amyloid-beta-targeting monoclonal antibodies probably result in little to no difference in cognitive function and dementia severity at 18 months. It does not support these antibodies as a meaningful treatment for cognitive symptoms in people with mild cognitive impairment or mild dementia due to Alzheimer's disease.
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Reduction of amyloid via amyloid-targeting therapies may result in clinical benefit.
Why it matters
This secondary analysis of a randomized trial included 1,582 participants, with 766 receiving donanemab and 816 receiving placebo, and noted that reducing amyloid may result in clinical benefit. It reports on posttreatment amyloid levels and clinical outcomes but does not provide a cure or prevention for Alzheimer's disease.
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This large review pooled 113 studies (nearly 30,000 people) comparing different forms of blood phosphorylated tau for detecting Alzheimer's pathology. p-tau217 was clearly the best-performing marker, correctly identifying disease pathology about 88% of the time, outperforming other tau variants like p-tau181.
Why it matters
Across 113 studies, blood p-tau217 identified Alzheimer's pathology about 88% of the time and outperformed other tau variants like p-tau181. The authors warn that about 90% of the pooled studies had a high risk of bias from lack of predefined thresholds, so the reported accuracy may be inflated.
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Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusive.
Why it matters
In this meta-analysis, among people with high amyloid, female sex was associated with faster tau accumulation in certain brain regions, and among APOE ε4 carriers female sex was associated with faster tau accumulation in the inferior temporal region. The authors suggest these sex differences call for sex-specific timing considerations when giving anti-amyloid and anti-tau therapies, but no treatment was tested here.
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Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD).
Why it matters
This meta-analysis examined how the APOE gene, sex and ancestry relate to three core CSF Alzheimer's biomarkers. It is about understanding risk and biomarker patterns across groups, not about treating or preventing Alzheimer's.
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PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions.
Why it matters
In this cohort of 269,725 men with erectile dysfunction, starting a phosphodiesterase type 5 inhibitor was associated with a lower risk of developing Alzheimer disease compared with nonuse, with an adjusted hazard ratio of 0.82. Because this is an observational cohort study rather than a randomized trial, it shows an association and cannot prove that these drugs prevent Alzheimer's disease.
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Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia).
Why it matters
This phase 3 trial tested masitinib, an oral drug targeting immune cells in the brain, as an add-on to existing dementia medications in people with mild-to-moderate Alzheimer's disease. It was a randomized, placebo-controlled study, so its results are needed to judge whether this drug affects the disease course.
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A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline.
Why it matters
In this large multicenter PET study, cognitively unimpaired people who were positive for both amyloid and tau had a substantially increased risk of progressing to mild cognitive impairment compared with those negative for both. This shows these PET markers can identify high-risk individuals, but it does not test any treatment or prevention.
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As a result, physicians struggle to interpret these models, and feel it is hard to trust them.
Why it matters
The text only notes that physicians struggle to interpret these models and find it hard to trust them. No information is given about whether the model improves diagnosis, treatment, or prevention of Alzheimer's disease.
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Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility.
Why it matters
In more than 1000 people from the Alzheimer's Disease Neuroimaging Initiative, blood p-tau181 was already raised before symptoms in people with amyloid on PET and rose further in mild cognitive impairment and Alzheimer's dementia. It separated Alzheimer's dementia well (AUC 85.3%) but amyloid-positive from amyloid-negative people less well (AUC 76.9%), and higher baseline levels predicted later dementia about as well as the spinal-fluid p-tau181 test. These are group-level results from a research cohort with no stated cut-off, so they do not show that one blood result can diagnose or forecast Alzheimer's in an individual.
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The neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer's disease (AD).
Why it matters
In 115 people who had blood drawn 8, 4 and 2 years before death and were then autopsied, plasma p-tau181 matched Alzheimer's brain pathology better than their clinical diagnosis did, and told Alzheimer's apart from other brain pathologies with high accuracy (AUC 97.4%, 95% CI 94.1–100%) even 8 years before death. It is a diagnostic finding from one cohort and does not show that measuring or lowering p-tau181 treats or prevents the disease.
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The NfL level was increased at baseline in patients with mild cognitive impairment and AD dementia (mean levels: cognitive unimpairment, 32.1 ng/L; mild cognitive impairment, 37.9 ng/L; and AD dementia, 45.9 ng/L; P Conclusions and relevance The findings suggest that plasma NfL can be used as a noninvasive biomarker associated with neurodegeneration in patients with AD and may be useful to monitor effects in trials of disease-modifying drugs.
Why it matters
In this cohort, higher plasma neurofilament light levels were seen in people with mild cognitive impairment and Alzheimer's dementia than in those without cognitive impairment. This suggests plasma NfL may be useful as a noninvasive marker of neurodegeneration, but the study does not show that measuring it changes treatment, prevention or cure.
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Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI).
Why it matters
In 11,409 Medicare beneficiaries with mild cognitive impairment or dementia whose cause was unclear to dementia specialists, clinical management changed within 90 days of an amyloid PET scan in 60.2% of those with MCI and 63.5% of those with dementia, above the study's 30% threshold. The study measured changes in management only, and the record describes no comparison group without a scan. The authors state that "further research is needed to determine whether amyloid PET is associated with improved clinical outcomes", so it shows no benefit to patients' health.
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Ann Neurol 2018;84:737-748.
Why it matters
Pooling individual data from 1,251 people with primary progressive aphasia (a language-led dementia) at 36 centres, this meta-analysis found brain amyloid (an Alzheimer's hallmark, measured by PET, spinal fluid or autopsy) in 86% of the logopenic variant but only 20% of the nonfluent and 16% of the semantic variants. The authors conclude that the current classification "helps to predict underlying pathology" and that age and ApoE genotype "should be considered" when reading amyloid tests in these patients. The study is about diagnosis, not treatment, and the variant alone does not settle any one person's result.
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Aerobic exercise in early AD is associated with benefits in functional ability.
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In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks.
Why it matters
In this double-blind trial, 640 people with mild to moderate Alzheimer disease were randomized to atorvastatin 80 mg a day or placebo for 72 weeks. All were already taking donepezil and had LDL cholesterol between 95 and 195 mg/dL. The statin did not improve cognition (ADAS-Cog, p = 0.26) or overall function (ADCS-CGIC, p = 0.73) compared with placebo, and it was generally well tolerated. It tested treatment in people who already had Alzheimer's, so it does not address whether statins affect the risk of developing dementia.
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76/100
The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes.
Why it matters
This database project combined many genetic association studies and confirmed the APOE epsilon4 allele as a risk factor while pointing to over a dozen other possible susceptibility genes. These results help guide research into the genetics of Alzheimer's disease, but they do not offer a treatment, cure or prevention.
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76/100
Two hundred eighty-eight patients had paired scans (mean interval 10.9 months).
Why it matters
In a placebo-controlled trial of the amyloid vaccine AN1792 in 372 people with probable Alzheimer's disease, "prematurely terminated owing to meningoencephalitis in a subset of patients", the 45 people who made antibodies lost more brain volume on MRI over about 11 months than placebo patients (3.12% vs 2.04%; p = 0.007) and had more ventricular enlargement. The authors report that this extra volume loss was not matched by cognitive change and say the reasons "remain unclear", one possibility being "amyloid removal and associated cerebral fluid shifts". Antibody responders are a subgroup of the vaccine arm rather than a randomised group, and the study does not show that the vaccine helped.
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This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD.
Why it matters
Plasma GFAP levels were higher in people with preclinical Alzheimer's disease than in cognitively unimpaired individuals without amyloid, and were linked to tau pathology only when amyloid pathology was also present. This points to plasma GFAP as a possible biomarker for detecting and tracking Alzheimer's disease, not as a treatment or cure.
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Exclusion criteria included any significant neurologic disorder other than suspected AD; presence of infection, infarction, or multiple lacunes as detected by magnetic resonance imaging; and any significant systemic condition that could lead to difficulty complying with the protocol.
Why it matters
Longitudinal changes in plasma p-tau181 were associated with cognitive decline and, unlike plasma NfL, were specific to Alzheimer's disease. This supports a blood marker for predicting and monitoring decline, not a treatment or cure.
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Of 490 participants, 251 were women (51.2%) and the mean (SD) age was 65.9 (13.1) years.
Why it matters
In 490 people (average age 65.9, 51% women), researchers asked "how early in the course of AD" blood levels of P-tau217 start to change compared with spinal-fluid and PET markers. Plotted against the amount of amyloid on PET, "both plasma and CSF P-tau217 were increased at lower Aβ-PET values compared with tau-PET measures", so the fluid marker moved before tau scans did on the amyloid scale. This is an association study of biomarkers for early detection, not a diagnostic accuracy test or a treatment result, and the record we hold gives no numbers for how much earlier.
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Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer's disease.
Why it matters
In the Swedish BioFINDER study, plasma p-tau217 increased over time in people with preclinical and prodromal Alzheimer's disease and in those with mild cognitive impairment who later converted to dementia, but it did not change in amyloid-negative participants or non-converters. This suggests p-tau217 could be used to monitor disease progression, but it is not a treatment, cure, or prevention.
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75/100
Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer's disease (AD), reflecting abnormal tau metabolism in the brain.
Why it matters
In 194 people from Sweden's BioFINDER study, the spinal-fluid marker p-tau217 tracked tau and amyloid brain scans more closely than the established marker p-tau181, rose more over time, and better separated Alzheimer's dementia from other neurodegenerative disorders. The tau-scan finding held in a second, independent group of 32 people, and the main results held with a different p-tau217 test kit. The authors conclude only that p-tau217 "might be more useful than p-tau181 in the diagnostic work up of AD"; the record gives no accuracy figures, and this is a lumbar-puncture test about detection, not a blood test or a treatment finding.
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Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear.
Why it matters
In 589 people from three cohorts, levels of a tau protein in blood (P-tau181) were higher at early, symptom-free stages of Alzheimer's and higher again at mild cognitive impairment and dementia. The blood test separated Alzheimer's dementia from other brain diseases with accuracy the authors describe as similar to spinal-fluid testing and tau PET scans (AUC 0.94–0.98), and high levels were associated with later Alzheimer's dementia. The authors conclude it "may be useful in clinical practice and trials"; it is a test, not a treatment, and the record does not report how well it predicts any one person's future.
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75/100
Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P Conclusions and relevance Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease.
Why it matters
In people with Alzheimer's dementia and mild cognitive impairment, plasma neurofilament light was higher and correlated with CSF neurofilament light and other markers. This supports it as a blood marker of nerve damage, not a treatment or cure.
From across this topic
10 of the 5,172 studies in this topic, picked by a fixed rule (a hash of each study's address), not by score or date; each page of this list shows a different 10. The same 10 appear here every time.
- The genetics of Alzheimer disease
- Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease.
- Comparison of a multi-analyte algorithmic immunoassay blood test with immunoprecipitation mass spectrometry for the detection of amyloid pathology
- The Vascular Hypothesis of Alzheimer's Disease: A Key to Preclinical Prediction of Dementia Using Neuroimaging
- Blood-brain barrier permeability changes and neuroinflammation in Alzheimer disease progression
- Bariatric Surgery Is Associated With Reduced Incidence of Mild Cognitive Impairment and Alzheimer Disease and Related Dementias: A Retrospective Cohort Study
- Alzheimer's disease and related dementias (ADRD) after COVID‐19 infection: trends and disparities
- Alzheimer-Related Cerebrovascular Disease in Down Syndrome
- Prognostic value of cerebrospinal fluid biomarkers in mild cognitive impairment due to Alzheimer disease
- Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change