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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Why it matters
Addresses neuroinflammation in Alzheimer's disease. The inflammatory side of the disease is treated as something to investigate, and no treatment is tested here.
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Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis.
Why it matters
Using autopsy findings from 4,914 brains rather than clinical diagnoses, this genetic study linked APOE variants to plaques, tangles, amyloid in blood vessels and Lewy body disease, and found new associations for plaque burden (GALNT7, ABCG1, a chromosome 9 region) and hippocampal sclerosis (KCNMB2). It confirmed 12 of 21 known non-APOE Alzheimer's risk genes, 9 of them with larger odds ratios than in clinically diagnosed samples. These are statistical associations that point to biology worth studying; they do not test any treatment or predict an individual's risk.
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Among the evaluated parameters, the only significant predictor of conversion to AD was non-Cp copper (hazard ratio = 1.23, 95% confidence interval = 1.03-1.47, p = 0.022); for each additional micromole per liter unit (μmol/l) of non-Cp copper, the hazard increased by ~20%.
Why it matters
In this study of people with mild cognitive impairment, higher levels of nonceruloplasmin copper in the blood were the only significant predictor of conversion to Alzheimer's disease. The authors suggest that lifestyle and dietary changes might modify this risk, but the study did not test whether such changes actually prevent conversion.
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Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD.
Why it matters
In this 24-week trial of 60 patients with amnestic mild cognitive impairment or mild Alzheimer disease, sodium benzoate improved cognitive and overall function scores compared with placebo. The authors describe the results as preliminary and promising for D-amino acid oxidase inhibition, so this is an early finding about symptom treatment, not proof of a cure or prevention.
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Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years.
Why it matters
In 201 cognitively normal adults followed up to 7.5 years, abnormal amyloid imaging and CSF biomarker levels were linked to faster time to cognitive impairment, though some with abnormal levels stayed cognitively normal for up to 6.6 years. The study supports biomarkers as signals of underlying Alzheimer pathology, but it does not test any treatment.
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This study updated a 2010 hypothetical model of major Alzheimer's disease (AD) biomarkers based on new evidence.
Why it matters
An updated version of the hypothetical model of how Alzheimer's biomarkers change as the disease progresses. It is still presented as hypothetical, and it is a way of tracking the disease rather than a way of treating or preventing it.
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64/100
Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo.
Why it matters
In this 24-week trial of 131 patients with depression of Alzheimer's disease, sertraline did not improve cognitive test performance compared with placebo. Treatment with sertraline was not associated with greater cognitive improvement, and depression remission also did not affect cognition.
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Twelve months' treatment with doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in AD.
Why it matters
In this randomized trial of 406 patients with mild to moderate Alzheimer's disease, there was significant deterioration on a cognitive scale over time with both rifampin and doxycycline compared with placebo, and no statistically significant decline when the two were used together. The trial did not confirm the preliminary suggestion that these antibiotics slow or stop Alzheimer's disease progression.
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The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD).
Why it matters
This study examined the accuracy of clinical diagnosis of Alzheimer's disease compared to neuropathological findings. It found that sensitivity and specificity varied, and it is about diagnosis, not treatment, cure, or prevention.
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We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD).
Why it matters
These guidelines give a practical way to assess Alzheimer's brain changes in examined brain tissue, using an "ABC" score that combines amyloid β deposits (A), the stage of neurofibrillary tangles (B) and neuritic plaques (C), along with recommendations on brain sampling, staining and reporting. They also recognise that Alzheimer's brain changes "may occur in the apparent absence of cognitive impairment", and they set out more detailed ways to record common co-existing conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis and TDP-43 inclusions. This is a standard for examining brain tissue, not a test for living patients or a treatment.
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Two phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI).
Why it matters
Two phase 3 trials found that rosiglitazone, added to ongoing cholinesterase inhibitor treatment, did not improve cognition or global function in mild-to-moderate Alzheimer's disease. This is a clear negative result: the drug did not help patients in these studies.
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Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial.
Why it matters
This study found that memory task functional MRI was feasible and had good test-retest reliability in people with mild Alzheimer disease, though larger and multisite studies are needed. It is about a brain imaging method for use in trials, not about treating, curing or preventing the disease.
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AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p 1).
Why it matters
In two small samples of cognitively normal adults, a pattern of cortical thinning predicted who later developed Alzheimer's dementia, with low thickness linked to higher risk. This is an early finding from small samples and would need confirmation before it could be used to guide care.
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Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the complement receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology.
Why it matters
This genetic follow-up found association between a CR1 risk haplotype and Alzheimer disease, strongest in APOE epsilon4 carriers, and a CR1 copy number variation producing different CR1 isoforms was also associated with risk. The findings implicate CR1 in Alzheimer disease genetic risk and possibly amyloid metabolism, but no treatment or cure is provided.
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64/100
Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer pathology and stroke through which vascular changes may influence dementia risk.
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These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
Why it matters
Higher plasma clusterin levels were associated with entorhinal cortex atrophy, greater disease severity, and faster clinical progression in Alzheimer's disease, and predicted greater amyloid burden in the medial temporal lobe. This identifies clusterin as potentially important in the disease process, but it does not provide a treatment or cure.
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64/100
Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years.
Why it matters
In 57 older adults without dementia from the Baltimore Longitudinal Study of Aging (mean age 78.7; six had mild cognitive impairment), people with more amyloid on a PiB brain scan had shown greater declines in mental status and verbal learning and memory over the years before the scan (mean follow-up 10.8 years), but not in visual memory. The authors conclude that higher amyloid is "associated with greater longitudinal decline in mental status and verbal memory in the preceding years." The study looked back from a single scan, so it shows an association. It does not show that the scan predicts future decline or that amyloid caused the decline.
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This study proposes a model that relates disease stages to Alzheimer's disease biomarkers.
Why it matters
Proposes a model of how biomarkers of the Alzheimer's pathological cascade change over the course of the disease. The authors label the model hypothetical, so it offers a framework for ordering biomarker measurements rather than a tested treatment.
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64/100
The authors conducted a large genome-wide association study using 2,032 individuals from France with Alzheimer's disease and 5,328 controls.
Why it matters
A genome-wide association study reporting variants at CLU and CR1 associated with Alzheimer's disease. The finding marks genes for further study and is not itself a treatment or a means of prevention.
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Factors influencing survival in Alzheimer disease include race/ethnicity and comorbid diabetes and hypertension.
Why it matters
This multiethnic, population-based study of incident Alzheimer's disease cases found that a history of diabetes and a history of hypertension were independently associated with a shorter lifespan. It also found that the median postdiagnosis survival duration was 3.7 years, and that no differences in lifespan were seen by race/ethnicity after multivariable adjustment.
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In nursing home residents with AD and psychosis, aripiprazole did not confer specific benefits for the treatment of psychotic symptoms; but psychological and behavioral symptoms, including agitation, anxiety, and depression, were improved with aripiprazole, with a low risk of AEs.
Why it matters
In this 10-week randomized, double-blind, placebo-controlled trial of 256 nursing home patients with Alzheimer disease and psychotic symptoms, aripiprazole showed no significant differences from placebo on the coprimary efficacy endpoints of psychosis score and clinical global impression severity. Some secondary measures suggested possible clinical benefits, but the primary outcomes were negative.
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There were no differences in measures of effectiveness between initiation of active treatments or placebo (which represented watchful waiting) but the placebo group had significantly lower health care costs.
Why it matters
This cost analysis compared second-generation antipsychotics with placebo for psychosis and aggression in people with Alzheimer's disease. It found no differences in effectiveness but lower health care costs with placebo, and it does not show a cure or prevention.
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64/100
Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD).
Why it matters
Smaller hippocampal and entorhinal cortex volumes on MRI each helped predict which people with mild cognitive impairment would later develop Alzheimer disease, but the added value beyond age and cognitive measures was small. Combining these MRI volumes with age and cognitive measures led to high levels of predictive accuracy.
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As a potential disease-modifying treatment for Alzheimer disease (AD), 3-amino-1-propanesulfonic acid (3APS) is a compound that binds to amyloid beta (Abeta), a toxic protein known to aggregate, leading to amyloid plaque deposition in the brain.
Why it matters
This Phase II study tested the compound 3APS, which binds amyloid beta, in 58 people with mild-to-moderate Alzheimer disease for safety, tolerability, and pharmacokinetic and pharmacodynamic effects. It was a small early-stage trial and does not establish that 3APS treats, cures, or prevents Alzheimer disease.
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Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimer's disease is disputed.
Why it matters
In this randomized controlled trial, patients with mild to moderate Alzheimer's disease received galantamine or placebo for 4 months, followed by a 4-month open-label extension in which all received galantamine. The available text does not report whether galantamine helped patients meet their treatment goals.
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.
- Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project
- Treatment strategies targeting amyloid β-protein
- Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease
- Role of Oxidative Damage in Alzheimer's Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery
- Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease
- microRNA-Based Biomarkers in Alzheimer's Disease (AD)
- Influence of microglial activation on neuronal function in Alzheimer's and Parkinson's disease dementia
- Subjective memory complaints, education, and risk of Alzheimer's disease
- Cost-Effectiveness and Value-Based Pricing of Aducanumab for Patients With Early Alzheimer Disease
- Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists