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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Compared with participants who learned that they had a not elevated amyloid result, individuals who learned of an elevated amyloid result were no more likely to experience short-term increases in depression (mean [SD] change in the Geriatric Depression Scale score, 0.02 [1.3] vs 0.04 [1.3]; P = .90), anxiety (mean [SD] change in State-Trait Anxiety Inventory score, -0.02 [3.2] vs -0.15 [3.0]; P = .65), or suicidality (mean [SD] change in the Columbia Suicide Severity Rating Scale score, 0.0 [0.4] vs -0.01 [0.5]; P = .67).
Why it matters
In this study of 1,167 participants with elevated amyloid and 538 with not elevated amyloid who had no cognitive impairment, learning an elevated amyloid result did not increase short-term depression, anxiety, or suicidality compared with learning a not elevated result. Those with elevated amyloid did have increased Concern About AD scores.
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We identified 2 core dimensions of heterogeneity: typicality and severity.
Why it matters
This review and meta-analysis found that Alzheimer's disease can be grouped into subtypes based on where tau-related pathology and brain shrinkage occur, with typical, limbic-predominant, hippocampal-sparing, and minimal atrophy forms. The authors propose that these subtypes may help frame future research into the disease's mechanisms.
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Based on the current evidence, rTMS was an effective therapy for cognitive impairment in AD.
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Over a long period of observation, no evidence was found that a specific AHM drug class was more effective than others in lowering risk of dementia.
Why it matters
In people with high blood pressure, using any antihypertensive medication was linked to a reduced risk of developing dementia and Alzheimer's disease. This was a meta-analysis of observational studies, so it cannot prove that these medications directly prevent dementia.
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74/100
In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD.
Why it matters
In this 2-year trial of 195 cognitively intact people at risk for Alzheimer disease, low-dose naproxen did not reduce the rate of progression on the Alzheimer Progression Score and showed no notable treatment effects on cerebrospinal fluid, cognitive, or neurosensory markers. Naproxen-treated individuals also had a clear excess of adverse events, so this provides evidence that naproxen does not slow presymptomatic Alzheimer disease.
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Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies.
Why it matters
In people with inherited Alzheimer's disease, the rate of change of serum neurofilament light distinguished mutation carriers from non-carriers about a decade earlier than single measurements and predicted brain shrinkage and cognitive change. This is a marker of progression, not a treatment or cure.
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We performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls.
Why it matters
This meta-analysis found that serum brain-derived neurotrophic factor levels were significantly lower in patients with Alzheimer's disease than in healthy controls. It examines a possible marker in blood, not a treatment, cure, or prevention.
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This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine.
Why it matters
This large Phase III randomized controlled trial tested whether nilvadipine, a hypertension drug, could slow cognitive decline in people with mild to moderate Alzheimer's disease over 18 months. It was designed to test a possible disease-modifying effect, but the available text does not report whether it worked.
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Although prespecified criteria for testing treatment effects were not met, these data suggest a potential treatment effect in patients with mild AD treated with high-dose crenezumab.
Why it matters
In this phase 2 trial, crenezumab did not meet its primary or secondary endpoints for cognition or function. A post hoc analysis suggested reduced decline on one cognitive measure in the high-dose group and in milder patients, but this was not a prespecified result.
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Contrary to long-standing views, men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.
Why it matters
This analysis of many studies found that men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing Alzheimer's disease from age 55 to 85, though women had higher risk at younger ages. It also found no significant difference between men and women in converting from mild cognitive impairment to Alzheimer's disease.
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In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.
Why it matters
In this trial of 7540 men, vitamin E, selenium, and their combination were not associated with reduced dementia incidence compared with placebo. The study found no significant protective effect of these antioxidant supplements.
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Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia.
Why it matters
In 1,284 people from two cohorts (ADNI and Sweden's BioFINDER), higher plasma tau went with Alzheimer dementia and with CSF signs of Alzheimer pathology, but the correlations were weak and differed between the cohorts. The authors found "the overlap between normal aging and AD is large, especially in patients without dementia," and concluded the results "do not support plasma tau as an AD biomarker in individual people." In ADNI, higher plasma tau was linked with worse cognition, more atrophy and more hypometabolism over follow-up, but only at the group level.
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Avagacestat did not demonstrate efficacy and was associated with adverse dose-limiting effects.
Why it matters
In this randomized trial of 263 people with prodromal Alzheimer's disease, avagacestat did no better than placebo on key clinical measures and caused dose-limiting side effects. Participants identified by spinal-fluid biomarkers, whether given the drug or placebo, progressed to dementia more often and lost more brain volume than biomarker-negative participants. The authors also found that spinal-fluid tests and amyloid PET scans agreed closely enough that they suggest either one could be used to identify these patients.
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Computer-aided diagnosis of Alzheimer's disease (AD) is a rapidly developing field of neuroimaging with strong potential to be used in practice.
Why it matters
This study tested Random Forest classifiers using structural MRI measures for detecting and predicting Alzheimer's disease, including how robust they are across cohorts. It is about computer-aided diagnosis, not about treating, curing or preventing the disease.
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74/100
APOE ɛ4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism.
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APOE4 confers greater AD risk in women.
Why it matters
In 5,496 healthy older adults, carriers of the APOE4 gene variant were more likely to develop mild cognitive impairment or Alzheimer's, and the increase was larger in women than in men (hazard ratio 1.81 vs 1.27). Among 2,588 people who already had MCI, APOE4 raised the risk of progressing to Alzheimer's in both sexes (2.16 vs 1.64), but the sex difference was not statistically significant unless the analysis was limited to people with the APOE3/3 or 3/4 genotypes. In 980 ADNI participants, the APOE4 effect on spinal-fluid tau was more Alzheimer's-like in women with MCI, which the authors say "may be associated" with women's higher risk; this is an association, and the study tested no treatment.
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Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)?
Why it matters
In elderly people with mild cognitive impairment, high-dose B-vitamin treatment slowed shrinkage of brain regions vulnerable to Alzheimer's disease, and this benefit was confined to those with high homocysteine levels. This suggests that lowering homocysteine with B vitamins may slow brain atrophy and cognitive decline in this specific group, though it does not show the disease can be cured or prevented.
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At baseline, significantly higher Aβ burdens were noted in patients with AD (2·27, SD 0·43) and those with MCI (1·94, 0·64) than in healthy controls (1·38, 0·39).
Why it matters
At the start of this 2013 cohort study, people with Alzheimer's had the most amyloid (Aβ) in the brain on average, people with mild cognitive impairment had less, and healthy controls had the least (2·27, 1·94 and 1·38). The AD and MCI levels were significantly higher than the controls'. This shows amyloid levels are linked to disease stage, not that amyloid causes it. The record reports no results on later brain shrinkage or memory decline, and it tests no treatment.
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Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease.
Why it matters
This genetic study sequenced the genomes of 2,261 Icelanders to look for rare variants likely to affect protein function. It then tested those variants in people with and without Alzheimer's disease, and checked them in case-control groups from the United States, Norway, the Netherlands and Germany. The authors report a TREM2 variant associated with Alzheimer's disease risk, but the summary held here stops before the results, so see the original paper for which variant and how large the effect is. It identifies a genetic risk association and does not test any treatment, cure, or prevention.
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Avagacestat dosed at 25 and 50 mg daily was relatively well tolerated and had low discontinuation rates.
Why it matters
In this 24-week phase 2 trial of 209 patients with mild to moderate Alzheimer disease, discontinuation rates were higher in the 100-mg and 125-mg avagacestat dose groups, and trends for worsening cognition were observed in those groups. Exploratory cerebrospinal fluid biomarker analysis showed dose-dependent but not statistically significant reductions in a small subset of patients, so this drug did not demonstrate benefit and showed signs of harm at higher doses.
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The meta-analysis suggests a consistent moderate association between ADL and EF, supporting the growing evidence for a link between ADL and executive dysfunction in early dementia.
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Outcome measures were analyzed using repeated-measures analysis of covariance.
Why it matters
In this pilot trial of 104 adults with amnestic mild cognitive impairment or mild to moderate Alzheimer's disease, 20 IU of intranasal insulin improved delayed memory compared with placebo over 4 months. The authors state these results support longer trials, so this is preliminary and not an established treatment.
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The primary planned analyses did not show a significant treatment effect, but were confounded by unexplained variance.
Why it matters
In this 78-week trial, the planned analyses found no statistically significant differences between tramiprosate and placebo. Only after using adjusted models was a trend toward a treatment effect on cognition seen, and less hippocampus volume loss was found for both tramiprosate doses compared to placebo.
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74/100
No significant differences were found in the primary efficacy analysis.
Why it matters
In this phase 2 trial, 234 people with mild to moderate Alzheimer's disease were randomly assigned to placebo or one of four intravenous doses of bapineuzumab, an antibody against amyloid-beta, given every 13 weeks with final assessments at week 78. The main planned analysis found no significant difference from placebo on the cognition (ADAS-Cog) and daily-function (Disability Assessment for Dementia) scales, and the authors classed the trial as providing "insufficient evidence to support or refute a benefit." Possible differences seen only in exploratory analyses led the authors to recommend a phase 3 trial "with special attention to APOE epsilon4 carrier status"; on their own, these differences do not show that the drug works.
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The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.
Why it matters
In 6,989 people aged 55 or older who were followed for an average of 6.8 years, those whose pharmacy records showed 24 months or more of NSAID use had a lower risk of Alzheimer's disease (relative risk 0.20, 95% CI 0.05 to 0.83). Shorter use showed no clear difference, and no NSAID use was linked to lower vascular-dementia risk. Because this is an observational study and the estimate is very imprecise, the authors say only that long-term use "may protect" against Alzheimer's disease; it does not show that taking NSAIDs prevents it.