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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Accumulating data suggest that cerebrovascular disease contributes to Alzheimer's disease pathophysiology and progression toward dementia.
Why it matters
This cohort study found that cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline. The findings suggest implications for Alzheimer's disease clinical trials and therapeutic development, but no treatment, cure or prevention was tested.
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In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk.
Why it matters
In this large genetic study, two rare APOE variants were linked to a 2-fold to 3-fold lower risk of Alzheimer disease, and carriers developed the disease more slowly with age. The authors say these findings could help guide drug development targeting APOE, but no treatment has yet been tested or shown to work.
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The chronological progression of brain atrophy over decades, from pre-symptomatic to dementia stages, has never been formally depicted in Alzheimer's disease.
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Plasma Aβ42/Aβ40 is a robust measure for detecting amyloid plaques and can be utilized to aid in the diagnosis of AD, identify those at risk for future dementia due to AD, and improve the diversity of populations enrolled in AD research and clinical trials.
Why it matters
In 465 people from research cohorts in the US, Australia and Sweden, whose clinics collected and processed blood differently, one mass-spectrometry blood test (plasma Aβ42/Aβ40) agreed well with amyloid PET scans (AUC 0.84, rising to 0.88 when APOE ε4 status was added) and with spinal-fluid tests (AUC 0.85, rising to 0.93). The authors report that results were consistent across all three cohorts and similar in people with and without memory problems, so the test could help flag brain amyloid without a scan or lumbar puncture. It detects plaques, not dementia. It still misclassifies some people and is not a treatment.
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Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology of mild cognitive impairment (MCI) and Alzheimer's disease (AD).
Why it matters
This analysis of brain spectroscopy studies found patterns of metabolic changes, including signs of oxidative stress and mitochondrial dysfunction, in people with mild cognitive impairment and Alzheimer's disease. The findings suggest these processes may occur early and that the hippocampus is a sensitive region, but they do not show that treating these changes helps patients.
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These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences.
Why it matters
In 113 people with cerebral amyloid angiopathy-related inflammation, this study found the acute clinical and radiologic manifestations were transient and potentially relapsing, and supported the effectiveness of slow oral tapering off after IV corticosteroid pulses. These findings concern this inflammatory condition and its management, not a treatment, cure, or prevention for Alzheimer's disease itself.
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We tested whether dysregulation of cholesterol catabolism, through its conversion to primary bile acids (BAs), was associated with dementia pathogenesis.
Why it matters
This multi-part study found links between markers of cholesterol breakdown, brain amyloid, and brain shrinkage, but use of bile acid sequestrant drugs was not significantly associated with risk of all-cause dementia. It does not show that any medication changes dementia risk and does not establish cause and effect.
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Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage.
Why it matters
This study found that different ways of defining the AT(N) biomarker categories are not interchangeable, and that continuous tau and neurodegeneration measures predicted cognitive decline better than binary ones in cognitively impaired participants. This is about how to classify and predict using biomarkers, not about treating, curing, or preventing Alzheimer's disease.
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Higher educational level (standardized β = 0.23, P Conclusions and relevance Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau.
Why it matters
Among 260 people with Alzheimer's disease, higher education was associated with relative preservation of brain structure when exposed to tau, and women and younger patients also showed relative preservation. This is about factors linked to resilience to tau, not about a treatment or cure.
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Among 641 participants with CSF Aβ42 data and at least two 18F-florbetapir scans, 335 (52.3%) were male.
Why it matters
In 641 people who had at least two amyloid PET scans, higher stages of amyloid buildup were associated with lower spinal-fluid Aβ42 and higher P-tau from stage 1, higher T-tau and faster cognitive decline from stage 2, and brain shrinkage from stage 3, even after accounting for clinical diagnosis. This suggests that where amyloid has spread on a scan may track how far the disease has progressed. The authors conclude only that the staging "may be useful for monitoring patients throughout the course of AD". It describes associations, not causes, and it is not a treatment.
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Blood biomarkers able to diagnose Alzheimer disease (AD) at the preclinical stage would enable trial enrollment when the disease is potentially reversible.
Why it matters
This case-control study tested whether markers in plasma neuronal-enriched extracellular vesicles could predict Alzheimer disease in cognitively normal participants who later developed it. It is a validation study of a blood-based predictor, not a treatment, cure, or prevention.
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Blood pressure variability (BPV) has been shown to have predictive value over blood pressure (BP) levels alone in stroke patients.
Why it matters
Using data from 460 patients with mild-to-moderate Alzheimer disease in a randomized trial, this study found that patients in the highest quartile of blood pressure variability had greater cognitive deterioration on the ADAS-cog after 1 and 1.5 years than those in the lowest quartile. Day-to-day blood pressure variability was also associated with deterioration on cognition and disability measures.
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Despite the promise of a multitude of sensors and devices that can be applied, there are no agreed-upon standards for digital biomarkers, nor are there comprehensive evidence-based results for which digital biomarkers may be demonstrated to be most effective.
Why it matters
There are currently no agreed-upon standards for digital biomarkers, and no comprehensive evidence showing which ones work best for monitoring cognitive function at home. Embedded passive sensors are the most mature area of research, and some of these solutions could be offered to larger populations in the coming decade.
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The regulation of vasculature is a prominent causal component of probable AD.
Why it matters
This genetic analysis identified new genetic signals associated with Alzheimer's disease and confirmed some previously known ones. It found that regulation of blood vessels appeared to be a prominent causal component in probable Alzheimer's disease, but this is genetic research and does not provide a treatment.
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PD dementia (PDD) is associated with α-synuclein propagation, but coexistent Alzheimer's disease (AD) pathology may coexist.
Why it matters
This review of autopsy studies found that dementia in Parkinson's disease is linked to alpha-synuclein spread, but Alzheimer's disease pathology, cerebrovascular disease and TDP-43 may also contribute. It describes what is found in the brain after death and does not test any treatment or prevention.
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There were no racial differences in the frequency of cerebral ischemic lesions noted on results of brain magnetic resonance imaging, mean cortical standardized uptake value ratios for Pittsburgh compound B, or for amyloid-β42 concentrations in CSF.
Why it matters
In 1,255 older adults (173 African American, 1,082 non-Hispanic white), amyloid on PET scans, amyloid-β42 in spinal fluid and ischaemic lesions on MRI showed no racial differences, but spinal-fluid total tau was lower in African American participants (mean 293.65 vs 443.28 pg/mL), as was phosphorylated tau181. The authors say this tau gap "appear[s] to reflect" a race-by-APOE ε4 interaction and recommend that biomarker analyses adjust for race. It is an observational comparison with a much smaller African American group, and it does not show that tau test values should be read differently for individual patients.
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Our findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD.
Why it matters
In preclinical Alzheimer's disease, tau PET was associated with decreased global cognition, memory, and processing speed, while amyloid PET and cortical thickness were not. This suggests tau imaging may be more sensitive for early cognitive changes, but it does not show that any treatment targeting tau helps patients.
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Researchers performed a genome-wide association study of clinically diagnosed Alzheimer's disease and disease-by-proxy.
Why it matters
A genome-wide meta-analysis reporting new loci and functional pathways that influence Alzheimer's disease risk. Loci and pathways indicate where treatments might be sought; this work does not supply one.
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See Li and Donohue (doi:10.1093/brain/awy089) for a scientific commentary on this article.
Why it matters
This modelling work describes the order in which biomarkers change in dominantly-inherited Alzheimer's disease, using data from an observational study. It does not test any treatment, so it offers no direct evidence for treating, curing or preventing the disease.
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Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol.
Why it matters
In this 12-month trial of 46 cognitively normal adults, changes in cerebrospinal fluid Alzheimer disease biomarkers did not differ significantly between the simvastatin and placebo groups. A significant interaction between treatment group and baseline LDL was observed for one biomarker, but the study did not show a disease-modifying effect of simvastatin overall.
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A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD).
Why it matters
This systematic review identified several factors associated with decreased risk of Alzheimer's disease onset, including statins, light-to-moderate alcohol consumption, Mediterranean diet adherence, higher education, and physically and cognitively stimulating activities, while head injury, diabetes, smoking, and APOE ε4 were associated with increased risk. These are associations from reviewed studies, not proven treatments or cures.
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Regular, long-term, customized HE improved the executive function of community-dwelling older people with memory disorders, but the effects were mild and were not observed in other domains of cognition.
Why it matters
In this trial, home-based exercise improved one measure of executive function compared with usual care, but all groups declined on other cognitive measures with no significant differences between groups. This means exercise may have a limited cognitive benefit but did not prevent overall decline.
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Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P Conclusions and relevance Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time.
Why it matters
In 397 people from the Alzheimer's Disease Neuroimaging Initiative (95 with Alzheimer's dementia, 192 with mild cognitive impairment, 110 cognitively normal), levels of neurofilament light, a general marker of damage to nerve fibres, in spinal fluid were higher in every patient group than in controls (median 1479 pg/mL in Alzheimer's dementia, 1336 in MCI that progressed, 1182 in MCI that did not, versus 1047). The study also tested whether these levels tracked later cognitive decline, brain shrinkage and white-matter change. The values overlap a lot between groups, and the marker is not specific to Alzheimer's, so this says nothing about diagnosing an individual, treatment or prevention.
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In persons selected from a population-based study, elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration.
Why it matters
In cognitively normal people from the community, elevated amyloid levels at baseline were linked to worse cognition and imaging biomarkers, and to greater clinical decline and neurodegeneration over time. These findings are described as having implications for the design of randomized clinical trials for Alzheimer's disease.
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Classification of evidence This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect.
Why it matters
In this small pilot trial of 42 women with mild-to-moderate Alzheimer's disease, raloxifene showed no significant cognitive benefit compared with placebo. This drug did not help treat Alzheimer's disease in this study.
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.
- Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging
- Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, Part XV
- Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
- Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies
- ¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)
- Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses
- The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort
- EEG microstate complexity for aiding early diagnosis of Alzheimer's disease
- [Formula: see text]Practice effects and longitudinal cognitive change in clinically normal older adults differ by Alzheimer imaging biomarker status
- Multi-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease cases