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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63/100
The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention.
Why it matters
This large plasma proteomic study identified 38 proteins associated with incident dementia over five years, 16 of which were also associated with late-life dementia risk when measured nearly 20 years earlier. It identifies possible biomarkers and pathways but does not establish a treatment, cure, or prevention for Alzheimer's disease.
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To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer's Coordinating Center (NACC) data set.
Why it matters
This study identified distinct clinicopathologic clusters among people with TDP-43 proteinopathy, a brain pathology found in some dementia cases. It is about understanding the disease, not about treating, curing, or preventing Alzheimer's disease.
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The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases.
Why it matters
In cells and a mouse model, reducing LRP1 lowered tau uptake and spread between neurons, identifying LRP1 as a possible target for diseases involving tau spread. This is laboratory and animal work and does not yet show benefit in people.
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Tau hyperphosphorylation is an early step in tau-mediated neurodegeneration and is associated with intracellular aggregation of tau as neurofibrillary tangles, neuronal and synaptic loss, and eventual cognitive dysfunction in Alzheimer disease.
Why it matters
Measuring tau in spinal fluid collected repeatedly from people who were kept awake, given sodium oxybate, or allowed to sleep normally, researchers found that sleep loss changed phosphorylated tau differently depending on the site of the chemical change. Phosphorylated tau is an early step toward the tangles seen in Alzheimer's. The authors suggest this offers a mechanism by which lost sleep could raise Alzheimer's risk, though it is not proof that poor sleep causes the disease.
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This study investigated the effect of NLRP3 inflammasome function on tau pathology and Alzheimer's disease progression.
Why it matters
Reports that activation of the NLRP3 inflammasome drives tau pathology.
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TREM2 (triggering receptor expressed on myeloid cells 2) gene variants were reported to increase the risk of Alzheimer's disease (AD) and even other neurodegenerative diseases (frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)), but so far, no definite conclusion has been drawn.
Why it matters
This analysis of 39 papers found that three TREM2 variants were significantly associated with Alzheimer's disease risk. It does not test any treatment or prevention, so it only adds to understanding of genetic risk.
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Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD.
Why it matters
In 8448 UK Biobank participants, a variant near the VCAN gene was linked to white matter integrity, and white matter measures were genetically correlated with each other and with stroke, depression and Alzheimer disease. This is a genetic study of brain structure and does not test treatment or prevention.
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Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP.
Why it matters
In progressive supranuclear palsy, higher CSF neurofilament light chain and lower CSF phosphorylated tau 181 predicted faster decline over 52 weeks, and higher NfL in CSF or blood was linked to greater superior cerebellar peduncle atrophy. These are markers of progression, not treatments, cures, or preventive measures.
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Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders.
Why it matters
This study identified an apolipoprotein E-dependent molecular signature in microglia from models of ALS, multiple sclerosis, and Alzheimer's disease, and in microglia around amyloid plaques in human brains, with TREM2 inducing the APOE pathway. It describes a microglial pathway involved in neurodegenerative disease but does not test any treatment, cure, or prevention.
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Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits.
Why it matters
In a small randomized trial, older adults with mild cognitive impairment who took blueberry supplements for 16 weeks showed increased brain activation during a working memory task. This is preliminary evidence of enhanced neural response and is consistent with prior trials showing neurocognitive benefit in this at-risk group.
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63/100
Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD).
Why it matters
In this cross-sectional and longitudinal study, plasma neuronal-derived exosome levels of several synaptic proteins were significantly lower in Alzheimer's disease and frontotemporal dementia patients than in controls, and some were decreased years before dementia. These proteins correlated with cognition and may serve as biomarkers, but no treatment, cure, or prevention is reported.
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63/100
Higher concentrations may reflect the intensity of the disease in FTD and are associated with more rapid atrophy of the frontal lobes.
Why it matters
In 74 people with frontotemporal dementia, average levels of the blood protein neurofilament light (NfL) were about four times those of 28 healthy controls (77.9 vs 19.6 pg/mL), but levels varied widely within each clinical and genetic group. The authors say higher levels "may reflect the intensity of the disease" and were associated with faster shrinkage of the frontal lobes. This small study compared patients with healthy people only, so it does not show that a blood NfL test can diagnose FTD or tell it apart from other conditions.
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When compared to post-mortem amyloid burden, low proposed thresholds were more sensitive than high thresholds (sensitivities: distribution volume ratiolow 81.0%, standard uptake value ratiolow 83.3%; distribution volume ratiohigh 61.9%, standard uptake value ratiohigh 62.5%) for CERAD moderate-to-frequent neuritic plaques, with similar specificity (distribution volume ratiolow 95.8%; standard uptake value ratiolow, distribution volume ratiohigh and standard uptake value ratiohigh 100.0%).
Why it matters
When PiB amyloid PET scans were checked against plaques counted in the brain after death, the commonly used "high" cut-offs caught only about 62% of brains with moderate-to-frequent plaques, while lower cut-offs caught 81–83%. The lower cut-offs gave up almost no specificity (95.8–100%), so the authors conclude that frequently applied PiB thresholds are "overly stringent in defining amyloid positivity." The record gives no threshold values, sample sizes or confidence intervals, applies only to the PiB tracer, and does not test any treatment.
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Among patients aged ≥55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation.
Why it matters
Among patients aged 55 and older with trauma, traumatic brain injury was linked to a 44% higher risk of developing Parkinson's disease over 5 to 7 years, with a dose response for repeated injuries. This is about Parkinson's disease risk and does not address treating, curing or preventing Alzheimer's disease.
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These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.
Why it matters
Among 749 nondemented participants, diabetes and poor glycemic control were associated with brain hypometabolism in Alzheimer signature regions but not with amyloid accumulation. The authors say these factors should be investigated in longitudinal studies, and no treatment, cure or prevention is reported.
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Studies with larger sample sizes, longer intervention periods, different fish oil dosages and genetic determinations should be investigated before definite recommendations can be made.
Why it matters
In this 12-month randomized trial of 36 people with mild cognitive impairment, the fish oil group showed significant improvement in short-term and working memory. The authors say larger studies with longer periods and different doses are needed before definite recommendations can be made, so this is a preliminary finding about memory, not a proven treatment or prevention.
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Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain.
Why it matters
This study found that measures of arterial stiffness and pulsatility were associated with silent subcortical infarcts, higher white matter hyperintensity volume, lower brain volumes, and lower memory and thinking scores. It identifies vascular factors linked to brain structure and function, not a treatment, cure, or prevention for Alzheimer's disease.
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The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases.
Why it matters
This 2011 genetic study identified a large GGGGCC repeat expansion in the C9ORF72 gene as the cause of ALS and frontotemporal dementia linked to chromosome 9p21. In Finland it accounted for 46.0% of familial and 21.1% of sporadic ALS, and it was found in one-third of familial ALS cases of European descent, which the authors called the most common genetic cause of these diseases identified to date. The study concerns ALS and FTD, not Alzheimer's disease, gives no FTD-only figures, and does not test any treatment.
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Baseline DBP and longitudinal increases in DBP were independently associated with a greater WMHV, and the association between DBP and WMHV was greatest among blacks.
Why it matters
In this stroke-free cohort, baseline diastolic blood pressure and increases in diastolic blood pressure over time were independently associated with greater white matter hyperintensity volume, with the strongest association among blacks. This is an observational link between blood pressure and a brain imaging measure, not evidence that any treatment prevents or cures Alzheimer's disease.
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Longitudinal fMRI provides a reliable indicator of brain activation over time, and may prove useful in identifying functional brain changes associated with cognitive decline on the trajectory toward clinical Alzheimer disease.
Why it matters
In this small longitudinal imaging study, older adults with mild clinical decline lost hippocampal brain activation over two years, while those without decline showed no change. It describes a brain change that tracks with decline but does not test or establish any treatment.
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Amyotrophic lateral sclerosis (ALS) is a common, fatal motor neuron disorder with no effective treatment.
Why it matters
Building on the authors' earlier finding that TDP-43 is "the major pathological protein in sporadic ALS", this 2007 study examined TDP-43 in 111 ALS cases, including inherited cases with and without SOD1 mutations. Its title reports that TDP-43 pathology distinguishes sporadic ALS from ALS caused by SOD1 mutations; the stored abstract stops before the results, so the proportions are not shown here. It concerns amyotrophic lateral sclerosis, not Alzheimer's disease, and does not directly inform Alzheimer's treatment, cure or prevention.
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The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study.
Why it matters
In this MRI substudy of a vitamin E and donepezil trial, no treatment effect on brain atrophy rates was confirmed for either treatment group. The results support using MRI as a measure of disease progression in trials, not as a treatment.
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White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia.
Why it matters
People with high blood pressure, and especially those with long-lasting high blood pressure, had more white matter lesions on brain scans. This links high blood pressure to brain changes thought to matter in dementia, but it does not test whether treating blood pressure prevents dementia.
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A total of 62 RCTs comprising 200,068 participants were included.
Why it matters
This network meta-analysis of 62 RCTs found that only high-dose dapagliflozin significantly reduced delirium and depression, and dulaglutide and liraglutide were associated with cognitive improvement. No significant benefits were observed for dementia or coma across all agents.
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Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk.
Why it matters
In this trial, higher blood carotenoid levels at the start were linked to slower cognitive decline only in people who carry the APOE ε4 gene, not in non-carriers. This suggests that diet-related factors might help offset genetic risk, but the finding comes from a subgroup of 442 participants and needs confirmation.