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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An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors.
Why it matters
Among 322 people without dementia who were followed for a median of 23.5 years, those with two or more vascular risk factors in midlife (mean age 52) were more likely to have elevated amyloid on a florbetapir PET brain scan later in life: 61.2% did, compared with 30.8% of those with none (adjusted odds ratio 2.88; 95% CI 1.46–5.69). The same link was not statistically clear for risk factors measured in late life. The authors say this is "consistent with a role of vascular disease in the development of Alzheimer disease". The study is observational and measured amyloid on scans, not dementia, so it does not show that treating these risk factors prevents Alzheimer's disease.
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Patients with MCI with APOEε4, abnormal CSF τ level, hippocampal and medial temporal lobe atrophy, entorhinal atrophy, depression, diabetes, hypertension, older age, female gender, lower MMSE score and higher ADAS-cog score, had a high risk for the progression to AD.
Why it matters
This review of 60 studies found that several factors, including abnormal cerebrospinal fluid proteins, brain shrinkage in certain regions, and the APOEε4 gene, were linked to a higher risk of progressing from mild cognitive impairment to Alzheimer's disease. These markers may help predict who will develop the disease, but the review does not show that any treatment targeting them can prevent it.
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Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Why it matters
This study pooled family records from 387 families carrying inherited Alzheimer's mutations (174 different mutations). In the 1,307 affected people whose age at symptom onset was known, that age tracked closely with their parent's onset age and with the typical onset age for their mutation and family, even after accounting for APOE type and sex. The authors conclude this supports using family history and mutation type to estimate expected onset in clinical research. It applies only to this rare inherited form of Alzheimer's, does not give individuals an exact onset date, and does not test any treatment.
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75/100
Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol.
Why it matters
In this randomized trial of 406 individuals with mild to moderate Alzheimer disease and normal lipid levels, simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment.
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During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias.
Why it matters
In 750 people with mild cognitive impairment followed for at least two years across 12 centres in Europe and the US, the 271 who went on to be diagnosed with Alzheimer's had, at the start, lower spinal-fluid amyloid-beta 42 and higher total tau and phosphorylated tau than those who did not. The authors say these markers identified incipient Alzheimer's "with good accuracy, but less accurately than reported from single-center studies", and that the amyloid-beta test varied considerably between sites, so they called for standardised lab methods. The study measured prediction only; the values for the two groups overlapped widely, so a single result cannot say for certain what will happen to one person.
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The purpose of this study was to use serial imaging to gain insight into the sequence of pathologic events in Alzheimer's disease, and the clinical features associated with this sequence.
Why it matters
This 2009 study repeated PIB and MRI imaging in people who were cognitively normal, had mild cognitive impairment or had Alzheimer's disease, to learn the order in which disease changes happen. PIB retention rose by a small amount each year in all participants (median 0.042 ratio units/year, P < 0.001), and the yearly rise did not differ between the three groups (P = 0.90); the authors concluded that "significant plaque deposition occurs prior to clinical decline." It is an observational imaging study: it tested no treatment, our record does not include its MRI results, and timing alone does not show that plaque causes the decline.
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Exercise training for patients with Alzheimer disease combined with teaching caregivers how to manage behavioral problems may help decrease the frailty and behavioral impairment that are often prevalent in patients with Alzheimer disease.
Why it matters
In this randomized trial, 153 people with Alzheimer disease living at home took part with their caregivers. Pairs received either a 3-month home programme that combined exercise with training caregivers to manage behaviour problems, or routine medical care. At 3 months, more people in the programme exercised at least 60 minutes a week (OR 2.82) and had fewer days of restricted activity (OR 3.10). The authors concluded that the combined programme "improved physical health and depression". The stored summary is cut before the depression and physical-function figures and reports no result on delaying nursing-home placement, so those effects cannot be checked here.
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Midlife p-tau181 was associated with faster 11-year memory decline beginning 20 years later in the ARIC cohort, which underscores a potentially long prodromal phase of cognitive decline that could precede dementia onset.
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Citalopram is effective in treating agitation in Alzheimer's dementia (AD), but it is associated with cognitive and cardiac risks, likely due to its R-enantiomer.
Why it matters
In this trial, escitalopram was not effective in treating agitation in Alzheimer's dementia and was associated with cardiac risks. The randomized sample was smaller than planned.
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AUC for amyloid and tau PET provide expert recommendations for clinical use of these technologies in the evolving landscape of diagnostics and therapeutics for Alzheimer's disease.
Why it matters
This workgroup updated appropriate use criteria for amyloid PET and developed criteria for tau PET, rating 17 clinical scenarios. For amyloid PET, seven scenarios were rated appropriate, two uncertain, and eight rarely appropriate; for tau PET, five were appropriate, six uncertain, and six rarely appropriate.
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Of 236 eligible participants screened, 43 were excluded.
Why it matters
In people with dominantly inherited Alzheimer disease, the drug gantenerumab reduced a cerebrospinal fluid marker of synaptic damage (neurogranin) compared with placebo. This supports the idea that reducing fibrillar amyloid affects processes related to neuroinflammation and neurodegeneration, though the study looked at biomarkers rather than whether patients felt or functioned better.
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With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical.
Why it matters
A blood test measuring plasma %p-tau217 performed as well as or better than FDA-approved cerebrospinal fluid tests at detecting amyloid plaques and tau tangles. This concerns diagnosis in people who might qualify for existing disease-modifying therapies, not a new treatment, cure or prevention.
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Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
Why it matters
This meta-analysis of 19 publications with 23,202 participants found small improvements over placebo on some cognitive and functional scales with anti-amyloid antibodies, but none of the differences met the minimal clinically important difference. It also found significantly increased risks of amyloid-related imaging abnormalities, so the benefits appear small and come with harms.
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In a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment.
Why it matters
In cognitively unimpaired older adults, higher baseline amyloid PET and plasma P-tau217 were linked to faster cognitive decline and progression to functional impairment, with P-tau217 the best predictor overall. These markers may help predict decline, but the study does not show that any treatment, cure, or prevention works.
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Based on the results of the prespecified coprimary endpoints, this study was negative.
Why it matters
In this trial of 238 participants with mild-to-moderate Alzheimer disease, semorinemab reduced decline on the ADAS-Cog11 at week 49, but the study was negative based on its prespecified coprimary endpoints because the effect did not extend to improved functional or global outcomes. The authors say these results may warrant further exploration of semorinemab or other anti-tau therapies.
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74/100
Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial.
Why it matters
In this phase 3 trial of 1736 people with early symptomatic Alzheimer's disease, donanemab, an antibody designed to clear brain amyloid plaque, slowed decline on a cognitive and functional scale compared with placebo over 76 weeks. The trial reported that 23 of 24 gated outcomes were statistically significant, and it was conducted in people selected for amyloid and low/medium or high tau pathology.
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74/100
This is the pivotal Phase 3 trial for donanemab in 1,736 people with early symptomatic Alzheimer's. Donanemab slowed decline on a combined cognitive/functional scale (iADRS) by about 22-35% relative to placebo over 76 weeks, depending on tau levels at baseline.
Why it matters
In the Phase 3 TRAILBLAZER-ALZ 2 trial, donanemab slowed decline on a combined cognitive/functional scale by about 22-35% relative to placebo over 76 weeks, depending on baseline tau levels. Brain swelling occurred in 24% of donanemab patients versus 2.1% on placebo, and three deaths in the donanemab group were considered treatment-related.
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This is the primary Phase 3 Clarity AD trial report for lecanemab.
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Data from 17 107 individuals (321 Asian, 635 Black, 829 Hispanic, and 15 322 White) with MCI or dementia and amyloid PET were analyzed between April 2020 and January 2022.
Why it matters
Among people with mild cognitive impairment or dementia, White participants were more likely to have a positive amyloid PET scan than Asian and Hispanic participants, but not more likely than Black participants. This describes differences in who tests positive for amyloid and does not show that any treatment, cure, or prevention works differently by race or ethnicity.
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Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate.
Why it matters
In this randomized clinical trial, treatment with levetiracetam did not change NIH-EXAMINER composite scores or secondary measures compared with placebo. The study found no significant benefit of levetiracetam on cognition in patients with Alzheimer disease.
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Despite significant progress, applications of astrocyte biomarkers in AD remain in their early days.
Why it matters
This meta-analysis found that CSF GFAP and YKL-40 and blood S100B were consistently increased in people with Alzheimer's disease. The authors state that applications of astrocyte biomarkers in Alzheimer's disease remain in their early days, and no treatment, cure, or prevention was tested.
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At randomization, the mean age is 72, 50% female, 77% with CDR-global score 0.5, and mean MMSE score 23.8.
Why it matters
In this 24-week phase 2 trial in mild Alzheimer's disease, the drug neflamapimod did not improve the main or secondary clinical measures compared with placebo. It did significantly lower spinal-fluid levels of total tau and p-tau 181, markers of nerve damage and tau disease. Combined with signals in people with the highest drug levels, the authors argue a longer, higher-dose study is warranted, so any clinical benefit remains unproven.
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A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial.
Why it matters
In this 36-week trial of 818 people with mild-to-moderate Alzheimer's dementia, those taking sodium oligomannate (GV-971) showed a significant difference in cognitive scores favoring the drug compared with placebo. The study reports this as an improvement in cognition, but it did not show that the drug cures or prevents Alzheimer's disease.
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Furthermore, plasma p-tau231 was significantly increased in amyloid-β PET quartiles 2-4, whereas CSF p-tau217 and plasma p-tau181 increased only at quartiles 3-4 and 4, respectively.
Why it matters
In this study, a new blood test for p-tau231 was already raised in people with only slight amyloid build-up (the second-lowest of four amyloid-PET bands), before the level at which an amyloid PET scan is called positive; spinal-fluid p-tau217 and blood p-tau181 rose only in higher bands. The authors report that it identified clinical stages of Alzheimer's and neuropathology equally well as blood p-tau181, so its advantage is earlier detection rather than better accuracy. It is a biomarker study comparing groups, not a treatment, and it does not show what a single person's result means.
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Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology.
Why it matters
This study found that changes in blood p-tau181 occurred early and were associated with amyloid-beta pathology and with later widespread tau aggregation. It concerns a potential diagnostic and screening blood biomarker and does not test any treatment, cure, or prevention.
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.
- Extended results of the Alzheimer's disease anti-inflammatory prevention trial
- Longitudinal β-Amyloid Deposition and Hippocampal Volume in Preclinical Alzheimer Disease and Suspected Non-Alzheimer Disease Pathophysiology
- Amyloid Precursor Protein and Alzheimer's Disease
- Navigating the introduction of anti-amyloid therapy in Europe: a position statement by individual members of the EADC
- The landscape of autosomal-dominant Alzheimer’s disease: global distribution and age of onset
- A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
- Rates of β-amyloid accumulation are independent of hippocampal neurodegeneration
- A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
- Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration
- Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders