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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Alzheimer's disease is one of the most heritable diseases in elderly people and the most common type of dementia.
Why it matters
This study assessed how the APOE gene and 23 other genetic variants affect the cumulative risk and age at which Alzheimer's disease and dementia begin, in a community-based cohort. Understanding genetic risk may help identify people at higher risk, but it does not provide a treatment or cure.
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In older cognitively unimpaired individuals (≥50 years), widespread, age-related elevated tau signal was seen among those with normal or abnormal amyloid status as compared to younger cognitively unimpaired individuals (30-49 years).
Why it matters
This study found widespread, age-related elevated tau signal in older cognitively unimpaired individuals, with more frequent regional tau elevation in those with abnormal versus normal amyloid. It suggests early tangle pathology may develop widely rather than only by region-to-region spread before clinical symptoms, which may inform understanding of how Alzheimer's disease begins, but it reports no treatment or cure.
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The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.
Why it matters
Using a single amyloid-PET scan from each of 667 people in the Alzheimer's Disease Neuroimaging Initiative, this study proposed a 4-stage order in which amyloid appears in the brain, from "temporobasal and frontomedial areas" to "finally the striatum"; only 2% of participants did not fit that order. The earliest stages were "mostly missed" by the usual positive/negative reading of a scan, yet were linked to lower amyloid (Aβ42) in spinal fluid, and later stages were most common in people with Alzheimer's dementia. Because the order was inferred from one scan per person rather than followed over time, the authors say only that it "may be used" to stage amyloid in an individual.
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We tested the hypothesis that cerebral amyloid angiopathy (CAA) is related to Alzheimer disease (AD) dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology and other common age-related neuropathologies.
Why it matters
This longitudinal study tested whether cerebral amyloid angiopathy is related to Alzheimer's disease dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology. It followed 1,113 participants from two longitudinal clinical-pathologic studies of aging with annual cognitive testing for a mean of 7.1 years before death.
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The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease.
Why it matters
This review of 30 years of Alzheimer's drug development found that only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy for marketing approval. The other drugs tested were probably ineffective, though inadequate clinical development methods have also been blamed for the failures.
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Out of the 664 studies screened, five studies met eligibility criteria.
Why it matters
This systematic review and meta-analysis of five prospective cohort studies found that higher adherence to the Mediterranean diet was associated with a reduced risk of developing mild cognitive impairment and Alzheimer's disease, and a reduced risk of progressing from mild cognitive impairment to Alzheimer's disease. The authors note the overall number of studies is small and call for further prospective cohort studies and randomized controlled trials.
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70/100
Cancer survivors had a lower risk of Alzheimer's disease than those without cancer, and patients with Alzheimer's disease had a lower risk of incident cancer.
Why it matters
In this cohort, cancer survivors had a lower risk of probable Alzheimer's disease (hazard ratio 0.67), and participants with probable Alzheimer's disease had a lower risk of subsequent cancer (0.39). Survivors of smoking related cancer had a substantially increased risk of stroke (2.18), showing the relationship is not simply protective across all conditions.
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The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia.
Why it matters
In 2011 an international expert workgroup convened by the National Institute on Aging and the Alzheimer's Association proposed research criteria for a "preclinical" stage of Alzheimer's disease, the years when the disease process "is thought to begin" before dementia is diagnosed. The aim was a "common rubric" for long-term studies to test which factors best predict who moves from normal cognition to mild cognitive impairment and dementia; it is an expert proposal, not a study that tested patients. The authors state the criteria are "solely intended for research purposes and do not have any clinical implications at this time," and that the link between the disease process and symptoms still needs to be clarified.
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81 participants with probable Alzheimer's disease and 69 healthy controls were assessed.
Why it matters
This multicentre phase 2 diagnostic study found that florbetaben (18F) PET scans distinguished patients with probable Alzheimer's disease from healthy controls, with significantly higher tracer uptake in neocortical grey-matter regions in the Alzheimer's disease participants. The authors describe it as a potential visual adjunct in diagnosis, so it is a diagnostic imaging study, not a treatment or cure.
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Pioglitazone was generally well tolerated in this pilot study.
Why it matters
In this small pilot trial, pioglitazone was associated with peripheral edema more often than placebo, and no significant treatment effect was observed on exploratory analysis of clinical efficacy. The study was primarily designed to evaluate safety in nondiabetic patients with Alzheimer's disease.
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The APOE epsilon4 allele is associated with the risk of late-onset Alzheimer's disease.
Why it matters
This longitudinal study followed cognitively normal subjects to determine when memory decline diverges among those with different APOE epsilon4 statuses. It found that the age at which memory decline diverges among homozygous carriers, heterozygous carriers, and noncarriers was previously unknown.
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70/100
Use of donepezil by AD patients resulted in significant delays in NHP.
Why it matters
In this follow-up of patients from earlier trials, taking donepezil at 5 mg per day or more was associated with significant delays in nursing home placement. This concerns a symptomatic treatment effect on placement timing and does not show that donepezil cures or prevents Alzheimer's disease.
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High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.
Why it matters
In the Rotterdam Study, 5,395 Dutch adults aged 55 or older without dementia had their diets assessed and were followed for a mean of 6 years, during which 146 developed Alzheimer's disease. After adjustment for factors including age, smoking, education and supplement use, higher dietary intake of vitamin C and vitamin E was associated with a lower rate of Alzheimer's (rate ratio 0.82 per 1-SD increase for each, with confidence intervals reaching 0.99 and 1.00). Beta carotene and flavonoids were linked to lower risk among current smokers. This is an observational association about food, not supplements; the authors conclude only that high intake "may lower the risk", and the study does not show that antioxidants prevent Alzheimer's.
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These results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.
Why it matters
In 801 older Catholic nuns, priests and brothers without dementia, followed for an average of 4.5 years, 111 developed Alzheimer's disease; those who reported doing mentally stimulating activities (such as reading a newspaper) more often at the start were less likely to be among them — each 1-point higher score on a composite activity scale was linked to a 33% lower risk (hazard ratio 0.67, 95% CI 0.49–0.92) after accounting for age, sex and education. The authors report similar results when people with early memory problems were excluded or APOE ε4 was taken into account, and higher activity was also linked to slower decline in thinking skills. This is an observational study in an unusual group of people, so it shows an association, not that more mental activity prevents Alzheimer's.
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Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD.
Why it matters
Of more than 50 ginkgo studies reviewed, only 4 were rigorous enough (double-blind, placebo-controlled, clearly diagnosed Alzheimer's) to pool. Together they showed "a small but significant effect" of 3–6 months of 120–240 mg Ginkgo biloba extract on objective tests of thinking (effect size 0.40). The trials found no significant side effects, but the authors note "2 case reports of bleeding complications". This is a modest effect on test scores, not evidence that ginkgo prevents or slows the disease.
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The presence of an APOE-epsilon4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype.
Why it matters
In 1,079 older Medicare recipients in one New York City community, followed from 1991 to 1996, carrying at least one APOE-ε4 copy (compared with the ε3/ε3 genotype) was linked to a 2.5-fold higher Alzheimer's risk in whites (95% CI 1.1–6.4), but no significant increase was found in African Americans (RR 1.0) or Hispanics (RR 1.1). Among people without ε4, the risk to age 90, adjusted for education and sex, was 4.4 times higher for African Americans and 2.3 times higher for Hispanics than for whites. The authors suggest "other genes or risk factors" may explain this; the study shows associations only, did not identify those factors, and tested no treatment or prevention.
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Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8).
Why it matters
This large analysis of many studies confirmed that carrying the APOE epsilon4 version of the apolipoprotein E gene raises the risk of Alzheimer's disease, with two copies raising risk far more than one, while the epsilon2 version was linked to lower risk. The strength of the epsilon4 link was weaker in African American and Hispanic groups, and the study did not test any treatment or prevention.
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Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression.
Why it matters
In this two-year single-blind study of 48 patients with probable Alzheimer's disease, desferrioxamine treatment led to a significant reduction in the rate of decline of daily living skills, while placebo and no-treatment groups did not differ. The authors concluded that sustained desferrioxamine may slow clinical progression, though the study was small and single-blind.
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This expert workgroup review summarizes what is known about ARIA, the brain-swelling (ARIA-E) and micro-bleeding (ARIA-H) side effect seen with anti-amyloid drugs.
Why it matters
This workgroup review reports that ARIA occurred in about 12.6%/17.3% of lecanemab patients and 24%/31% of donanemab patients in pivotal trials, with most cases mild or symptom-free but roughly 1-2% causing permanent disability or death. It warns that ApoE ε4 homozygotes face 2.5-5 times the risk and that ARIA symptoms can look like a stroke and must not be mistakenly treated with clot-busting drugs.
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Levels of plasma p-tau217 increased significantly in Aβ+ participants before showing significant deceleration (χ2 = 21.7; P Conclusions and relevance This study found that tau PET is valuable for both prognostic and real-time tracking of disease progression.
Why it matters
In participants from the A4 and LEARN studies, plasma p-tau217 increased significantly in amyloid-positive individuals before slowing down. The authors concluded that tau PET is valuable for both predicting and tracking disease progression in preclinical Alzheimer's disease.
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There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort to improve diagnostics, especially in the context of patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA is the driver of amyloid-related imaging abnormalities).
Why it matters
This meta-analysis compared five core cerebrospinal fluid biomarkers in people with sporadic cerebral amyloid angiopathy versus controls and/or patients with Alzheimer disease. It is about characterizing biomarkers of cerebral amyloid angiopathy, not about treating, curing or preventing Alzheimer disease.
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Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection.
Why it matters
An expert panel reviewed evidence that brain-wave (EEG) changes after COVID-19, such as slowing and a reduced alpha rhythm, resemble those seen in early Alzheimer's disease and related dementias. They propose that both share inflammation, reactive astrocytes (support cells), low oxygen and blood vessel injury. Routine EEG might help flag Long COVID patients at risk of cognitive decline, though the authors say this still needs to be studied.
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Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1-3 .
Why it matters
This study built a single-cell atlas of six brain regions from 283 post-mortem samples, identifying 76 cell types and vulnerable populations of excitatory neurons. It is a descriptive map of brain tissue and does not test a treatment, cure, or prevention for Alzheimer's disease.
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This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer's disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD.
Why it matters
This analysis found that almost all APOE4 homozygotes exhibited Alzheimer's disease pathology and had significantly higher levels of Alzheimer's biomarkers from age 55 compared to APOE3 homozygotes, with earlier symptom onset at 65.1 years. The study concludes that APOE4 homozygotes represent a genetic form of Alzheimer's disease, suggesting the need for individualized prevention strategies, clinical trials, and treatments.
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Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials.
Why it matters
This study used five cerebrospinal fluid biomarkers to build a staging model (stages 0-5) that tracked with other Alzheimer's biomarkers and predicted clinical decline. It suggests a single spinal fluid collection may help identify and stage Alzheimer's pathology, which could improve diagnosis and prognosis, though it is a biomarker model rather than a treatment.
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.
- Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage
- Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia
- Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease
- Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies
- A pilot study of fluorescence lifetime imaging ophthalmoscopy in preclinical Alzheimer's disease
- Cerebrovascular disease drives Alzheimer plasma biomarker concentrations in adults with Down syndrome
- Comparing clinical features of behavioral variant frontotemporal dementia and Alzheimer's disease using network analysis
- Specific hippocampal volume reductions in individuals at risk for Alzheimer's disease
- Neuropsychiatric symptoms are associated with progression from mild cognitive impairment to Alzheimer's disease
- Clinical features of Alzheimer's disease