Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Download bibliography of all 5,413 studies, highest score first: BibTeX (.bib) · RIS (.ris)
Highest usefulness score first. Studies without a score come last.
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Alzheimer's disease (AD) is a public health priority for the 21st century.
Why it matters
This genome-wide association study identified three new Alzheimer's disease-associated loci containing genes relevant for Alzheimer's disease and neurodegeneration, and reported that the association of SNPs in TOMM40 with Alzheimer's disease is potentially mediated by gene expression and DNA methylation. It states these loci may help elucidate biological mechanisms and warrant further exploration for potential precision medicine applications, so the work is preliminary and reports no treatment or cure.
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The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44-2·64, p Interpretation The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease.
Why it matters
This systematic review found that core CSF biomarkers and plasma total tau were strongly associated with Alzheimer's disease, while plasma Aβ42 and Aβ40 were not. It is about diagnosis, not treating, curing or preventing the disease.
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Resveratrol was safe and well-tolerated.
Why it matters
In this 52-week phase 2 trial of 119 people with mild to moderate Alzheimer disease, resveratrol was safe and well-tolerated and its metabolites reached the brain, but brain volume loss was increased compared with placebo. The authors state that further studies are required to interpret the biomarker changes associated with resveratrol treatment.
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These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.
Why it matters
In this 24-week trial of 404 people with moderate to severe Alzheimer's who were already on stable donepezil, those given memantine as well kept their cognition scores steady (+0.9 on a 0–100 scale), while those given placebo declined (−2.5). The authors report that adding memantine "resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated". However, only the cognition figures survive in this record. The trial covers only people already taking donepezil and only six months of treatment, so it supports memantine as an add-on in that group. It does not show that memantine slows the disease.
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Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells.
Why it matters
Using blood DNA from 1,362 people with Alzheimer's and 4,368 without, researchers found that clonal hematopoiesis (CHIP), an expansion of mutated blood stem cells, was linked to a lower risk of Alzheimer's dementia (odds ratio 0.64). The same mutations turned up in a microglia-rich fraction of the brain in seven of eight carriers, and genetic analyses supported a possible causal link. The authors say further studies are needed but suggest CHIP may help lower Alzheimer's risk.
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An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration.
Why it matters
In three cohorts totalling 1,016 cognitively unimpaired individuals, amyloid-beta was associated with increased plasma phosphorylated tau and an Alzheimer's-like pattern of tau accumulation only in people positive for astrocyte reactivity. The findings suggest astrocyte reactivity as an upstream event linking amyloid-beta with initial tau pathology and may help select participants for trials, but no treatment is tested.
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The mean CDR-SB score at baseline was approximately 3.2 in both groups.
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Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases.
Why it matters
By pooling genetic data from 1,126,563 people, this study found seven genetic regions linked to late-onset Alzheimer's disease that had not been identified before, and it points to microglia, immune cells and protein breakdown ("protein catabolism") as relevant. The authors say only "a fraction" of the genetic variants behind Alzheimer's are known and expect larger analyses to find more. These are risk associations to guide research, not a test, treatment or way to prevent the disease.
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80/100
Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease.
Why it matters
In this trial of 402 people with mild to moderate Alzheimer disease, DHA supplementation did not slow the rate of cognitive and functional decline compared with placebo. Brain volume decline was also similar between the DHA and placebo groups.
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Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD.
Why it matters
In this trial of 1684 patients with mild Alzheimer disease, tarenflurbil had no beneficial effect on the co-primary outcomes of cognition and activities of daily living compared with placebo. No significant differences occurred in the secondary outcomes.
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The double-cutoff approach revealed high confidence for interpreting scans as negative when Centiloid values were lower than 11 (95% CI, 9-13; I2 = 95%) and interpreting scans as positive if Centiloid values were higher than 26 (95% CI, 24-28; I2 = 95%).
Why it matters
This large analysis of amyloid PET scans found that scans could be confidently read as negative below a Centiloid value of 11 and positive above 26. Scans in the 11 to 26 range should be interpreted with caution depending on the context, which matters for how amyloid PET results are used in diagnosis.
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79/100
Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors.
Why it matters
In community-dwelling adults, midlife hypertension and diabetes were associated with faster increases in NfL and GFAP, while only Alzheimer's-specific biomarkers in midlife showed long-term associations with late-life dementia. All plasma biomarkers measured in late life were associated with late-life dementia, with NfL showing the largest association.
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Blood-based biomarkers (BBM) are becoming easily detectable tools to reveal pathological changes in Alzheimer's disease (AD).
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Among 171 Aβ-positive CU participants included in the main analyses, 119 (mean [SD] age, 73.0 [5.4] years; 60.5% female) were from the BioFINDER-1 study, and 52 (mean [SD] age, 64.4 [4.6] years; 65.4% female) were from the WRAP study.
Why it matters
This study followed people from two research cohorts, BioFINDER-1 and WRAP, who had amyloid in the brain but were described as cognitively unimpaired: 171 people in the main analyses. It asked whether blood markers predict later memory and thinking decline at this "preclinical" stage. The authors conclude that the blood test plasma P-tau217 "may be used as a complement to CSF or PET" when choosing participants for trials of new disease-modifying treatments. That is a finding about trial recruitment, not about a treatment, and our record does not include the figures showing how well the test predicted decline.
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The findings suggest that risk factors associated with ADRDs have changed over the past decade and differ based on sex and race and ethnicity.
Why it matters
This analysis estimates that about 1 in 3 Alzheimer disease and related dementia cases in the US are associated with 8 modifiable risk factors, most prominently midlife obesity, physical inactivity, and low educational attainment. It reports that these associated risk factors differ by sex and race and ethnicity, but it does not show that changing them prevents dementia.
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In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed.
Why it matters
In this phase 2 trial, 257 people with early symptomatic Alzheimer's disease, selected by PET scans showing amyloid and tau, were randomly assigned to donanemab or placebo infusions every 4 weeks for up to 72 weeks. At 76 weeks both groups had declined on the iADRS (0–144, lower is worse), by 6.86 points on donanemab vs 10.06 on placebo, a 3.20-point difference (95% CI 0.12 to 6.27; P = 0.04). Amyloid on PET fell 85.06 centiloids more than with placebo, but most secondary outcomes showed 'no substantial difference', brain edema or effusions (mostly asymptomatic) occurred with donanemab, and the authors, funded by Eli Lilly, say 'longer and larger trials are necessary'.
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Of 544 eligible participants (241 women and 303 men), the mean (SD) age was 74.3 (8.2) years, and the mean (SD) sMMSE score was 26.4 (1.9).
Why it matters
This trial tested whether minocycline could slow cognitive and functional decline in people with mild Alzheimer disease over 24 months. The available text does not report the main results, so no conclusion about its effect can be drawn from this summary.
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We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.
Why it matters
This analysis estimated the global burden of dementia and found that a portion of it could be attributed to modifiable risk factors like high BMI, high fasting plasma glucose, smoking, and high intake of sugar-sweetened beverages. It highlights the potential for prevention by addressing these factors.
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APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci.
Why it matters
Because APOE ɛ4 "may mask effects of other loci," this study looked separately at people without ɛ4 and found a new genome-wide significant signal in a region of chromosome 17 near MAPT, the gene for tau protein, where one SNP (rs2732703) accounted for the whole signal. The same variants were linked to activity of the nearby KANSL1 gene, and more weakly MAPT, in brain tissue, and an early-stage analysis suggested APOE may interact with a TMEM106B variant previously tied to frontotemporal dementia. The authors say the result needs replication in independent samples before the region's role is confirmed; it points to where to look, not to a treatment.
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Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline.
Why it matters
In this trial of 613 patients with mild to moderate Alzheimer disease, 2000 IU/d of alpha tocopherol resulted in slower functional decline compared with placebo, translating into a delay in clinical progression of about 6.2 months over the follow-up. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol.
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Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset.
Why it matters
In dominantly inherited Alzheimer's disease, declines in cerebrospinal fluid amyloid-beta 42 appeared 25 years before expected symptom onset, amyloid deposition and increased tau and brain atrophy 15 years before, cerebral hypometabolism and impaired episodic memory 10 years before, and global cognitive impairment 5 years before. The authors note these results require confirmation with longitudinal data and may not apply to patients with sporadic Alzheimer's disease.
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Liraglutide, a glucagon-like peptide 1 (GLP-1) agonist and antidiabetic drug, has shown neuroprotective effects in animal models.
Why it matters
In this phase 2b trial, liraglutide showed no significant difference in cerebral glucose metabolism, the primary outcome. A secondary cognitive measure performed better in liraglutide-treated patients, but no significant differences were seen in activities of daily living.
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Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target.
Why it matters
In this trial of 81 participants with Alzheimer disease, deferiprone accelerated cognitive decline on the primary outcome compared with placebo, driven by worsening performance on executive function tests, even though it decreased iron in the hippocampus. Hippocampal volume loss was not affected, and exploratory analysis found increased volume loss in some other brain regions with deferiprone.
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Overall, 1795 participants from Core and 1612 participants with at least one dose of lecanemab (Core + OLE) were included.
Why it matters
This report gives updated safety results from a phase 3 lecanemab study in early Alzheimer's disease, covering 1795 participants in the core study and 1612 who received at least one dose. It is about safety data and does not report on whether the drug cures or prevents the disease.
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78/100
These findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy and provide new insight into the adverse impact of ARIA.
Why it matters
This meta-analysis found that anti-β-amyloid drugs accelerated brain volume loss, with the amount varying by drug class. Secretase inhibitors accelerated atrophy to the hippocampus and whole brain compared to placebo.
From across this topic
9 of the 5,374 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 9. The same 9 appear here every time.
- APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases
- Mapping hippocampal and ventricular change in Alzheimer disease
- Alzheimer disease and cerebrovascular pathology: an update
- Cerebrospinal Fluid Markers of Synaptic Injury and Functional Connectivity in Alzheimer Disease: Protocol for a Cross-Sectional Study
- Association Between Dietary Biotin Intake and Dementia Risk, Including Alzheimer's Disease: A Prospective Study of 122 959 UK Biobank Participants
- Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides
- Comparison of cerebrospinal fluid levels of tau and Aβ 1-42 in Alzheimer disease and frontotemporal degeneration using 2 analytical platforms
- En respuesta a «Avances y controversias de los tratamientos de la enfermedad de Alzheimer»
- Druggable Pathophysiologic Targets in Alzheimer Disease: From Amyloid and Tau to Biomarker-Guided Multimodal Therapy