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.
-
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects.
Why it matters
In a three-stage genetic study of 85,133 people, the authors found three new protein-changing variants linked to Alzheimer's disease, including "a protective variant in PLCG2" (odds ratio 0.68, rarer in people with Alzheimer's than in controls) and "a risk variant in ABI3". The authors say the findings "implicate microglial-mediated innate immunity", meaning the brain's immune cells. These are rare-variant associations, not causes, and the study tests no treatment or prevention.
-
Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections.
Why it matters
This phase IIa trial of AN1792 immunization in people with mild to moderate Alzheimer's disease was stopped early because 6% of immunized patients developed meningoencephalitis. No significant differences were found between antibody responders and placebo groups on the cognitive and other measures assessed.
-
Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear.
Why it matters
Plasma p-tau217 and tau-PET performed similarly in predicting future cognitive decline among cognitively unimpaired individuals, and combining them was slightly better than either alone. Using plasma p-tau217 first and then tau-PET reduced the number of participants needed for a clinical trial by 94%, which could make preclinical Alzheimer's trials more efficient.
-
Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff < 0.007).
Why it matters
In a head-to-head comparison, the mass spectrometry-based %p-tau217WashU test performed significantly better than all immunoassays at identifying amyloid-PET, tau-PET, and cognitive abnormalities. The authors suggest %p-tau217 could serve as a stand-alone confirmatory test, while some immunoassays may be better suited as triage tests needing a second confirmation.
-
The APOE ε4 carriers and noncarriers were not significantly different at baseline (except for serum cholesterol level).
Why it matters
In this subgroup analysis of 1109 participants, the effect of a multidomain lifestyle intervention on cognition did not differ significantly between APOE ε4 carriers and noncarriers. The authors say whether benefits are more pronounced in carriers should be further investigated.
-
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide.
-
Although recent clinical trials targeting amyloid-β in Alzheimer's disease have shown promising results, there is increasing evidence suggesting that understanding alternative disease pathways that interact with amyloid-β metabolism and amyloid pathology might be important to halt the clinical deterioration.
Why it matters
This longitudinal study found that plasma GFAP was an early marker of amyloid-beta but not tau pathology in Alzheimer's disease. It concerns a biomarker and does not test a treatment, cure or prevention.
-
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness.
-
At week 32, compared with patients assigned to placebo (59 assessed), those assigned to rivastigmine (55 assessed) had improved step time variability for normal walking (ratio of geometric means 0.72, 95% CI 0.58-0.88; p=0.002) and the simple dual task (0.79; 0.62-0.99; p=0.045).
-
The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P = 0.001).
Why it matters
This randomized controlled trial found that B vitamin supplementation slowed the rate of brain atrophy in people with mild cognitive impairment, and that greater atrophy was associated with lower final cognitive test scores. It measured brain atrophy rates rather than whether dementia was prevented or cured.
-
Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer's disease (AD).
Why it matters
In 130 living people, microglial activation and tau accumulation were found to spread together across the brain in a Braak-like pattern. This links microglial activation to tau spread but does not test any treatment.
-
The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia.
Why it matters
In a randomised trial of 120 older adults, aerobic exercise training grew the front part of the hippocampus, a memory region that normally shrinks with age, by about 2% and improved spatial memory; in the control group hippocampal volume declined, and two other brain regions were unchanged. Larger gains went with higher blood levels of BDNF, a growth factor. The trial measured brain size and memory in ageing, not dementia or Alzheimer's disease.
-
Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years.
Why it matters
In 6,514 people, a positive tau PET scan was rare before age 50 but was estimated at 19% of cognitively unimpaired people by age 90, and at 79% of people with Alzheimer's dementia at age 75. Among cognitively unimpaired people, those positive on both amyloid and tau PET had an estimated 57% five-year risk of developing MCI or dementia, compared with 17% for amyloid-positive/tau-negative and 6% for people negative on both. The authors note this was a convenience sample and describe tau PET as a promising staging marker. These are associations, not a prediction for any one person.
-
Gradual up-titration of dose significantly reduced ARIA-E risk while demonstrating comparable pharmacokinetics/pharmacodynamics compared to standard dosing.
Why it matters
In this ongoing trial, a modified titration of donanemab reduced the frequency and severity of ARIA-E compared with standard dosing while maintaining similar amyloid reduction. This suggests that changing how the drug dose is increased may lower a key safety risk.
-
In BioFINDER-2, the mean (SD) age was 65.7 (14.4) with 261 females (52.7%).
Why it matters
In cognitively unimpaired people with initially low brain amyloid, combining plasma %p-tau217 and Aβ42/40 predicted subsequent amyloid accumulation better than either alone. This suggests blood biomarkers could help screen participants for primary prevention trials of antiamyloid therapies.
-
p75 neurotrophin receptor (p75 NTR ) signaling pathways substantially overlap with degenerative networks active in Alzheimer disease (AD).
Why it matters
In this 26-week phase 2a trial of 242 participants with mild to moderate Alzheimer's disease, the drug LM11A-31 met its primary endpoint of safety and tolerability and showed significant drug-placebo differences on some imaging and biomarker measures, but no significant effect on cognitive tests. The results suggest further investigation is warranted, but the drug has not been shown to improve thinking or memory.
-
The primary study randomized 272 participants (mean [SD] age, 75.2 [5.5] years; 145 female participants [53.3%]).
Why it matters
In these post hoc analyses of a donanemab trial, greater amyloid reduction was linked to better scores on a combined Alzheimer's rating scale only in APOE ε4 carriers. This is a secondary analysis of one trial and does not by itself establish how well the treatment works for patients overall.
-
There is emerging evidence linking fruit and vegetable consumption and cognitive function.
-
Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age.
-
The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.
-
Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma.
-
The experimental paradigm was feasible and acceptable.
-
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified.
Why it matters
This genetic study of FTLD-TDP, a fatal neurodegenerative disorder distinct from Alzheimer's disease, confirmed UNC13A and identified TNIP1 as risk factors and found subtype-specific risk genes. These findings have potential diagnostic and therapeutic implications but do not yet provide a treatment or cure.
-
With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study.
Why it matters
In this phase 2 trial, dextromethorphan-quinidine significantly reduced agitation scores compared with placebo in patients with Alzheimer disease. This suggests it may help treat agitation, though the study was designed as an early-phase trial.
-
A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).
Why it matters
This study tested a rare change in the TREM2 gene, called R47H, in 19,940 new people of European descent and pooled them with 28 earlier data sets. Across 24,086 people with Alzheimer's disease and 148,993 without, carriers had about 2.7 times the odds of having Alzheimer's (odds ratio 2.71). The study also looked at three other brain diseases and at amyloid and tau in spinal fluid, but those results are not in our record; it shows a genetic association in European-descent samples, not a cause, and reports no treatment or prevention.