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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This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and the plastic changes in the hippocampal-cortical network.
Why it matters
In this 8-week trial of only 30 participants, personalized rTMS improved cognitive and functional scores and increased connectivity between the hippocampus and precuneus compared with sham treatment. The small sample size means these results are preliminary and need confirmation in larger trials before rTMS can be considered a treatment for Alzheimer's disease.
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Tau plays a key role in Alzheimer's disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology.
Why it matters
In this phase 1b trial, an antisense oligonucleotide targeting tau was given to 46 patients with mild Alzheimer's disease and reduced cerebrospinal fluid total-tau in a dose-dependent way. Adverse events were mild or moderate and no serious adverse events occurred in treated patients, but this early trial was designed mainly to test safety, not whether it helps symptoms.
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For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P = .006; p-tau217 difference, 11%; 95% CI, 3%-20%; P = .003; p-tau231 difference, 15%; 95% CI, 5%-22%; P Conclusions and relevance Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework.
Why it matters
In this cross-sectional study, CSF p-tau at all four phosphorylation sites assessed was more closely associated with amyloid PET than with tau PET. The authors highlight the need for careful interpretation of p-tau biomarkers within the A/T/(N) framework; no treatment was tested.
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A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer's disease (AD) dementia.
Why it matters
A combination of plasma phospho-tau, brief cognitive tests and APOE genotype predicted progression to Alzheimer's dementia more accurately than memory clinic physicians' clinical predictions. This suggests a blood-based tool could improve prediction of who will develop dementia, though it is a prediction model and not a treatment.
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Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume.
Why it matters
In this secondary analysis of the SPRINT MIND trial, intensive blood pressure control was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, but no differences in other MRI biomarkers of Alzheimer's disease. The study does not show that intensive blood pressure control prevents or treats Alzheimer's disease.
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71/100
We found that accelerated increase in tau-PET signal was observed in amyloid-β-positive mild cognitive impairment (3.0 ± 5.3%) and Alzheimer's disease dementia (2.9 ± 5.7%), respectively, when compared to either amyloid-β-negative cognitively unimpaired (0.4 ± 2.7%), amyloid-β-negative mild cognitive impairment (-0.4 ± 2.3%) or amyloid-β-positive cognitively unimpaired (1.2 ± 2.8%).
Why it matters
This longitudinal PET study found that the rate of tau accumulation was greater in females and younger amyloid-positive individuals, while amyloid accumulation was greater in APOE ε4 carriers and older individuals. The authors say these findings are important for designing clinical trials and understanding factors linked to faster tau aggregation.
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The largest cohort, the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study (n = 3154), was the PET screening cohort used for a secondary prevention trial designed to slow cognitive decline associated with brain amyloidosis.
Why it matters
This analysis found a new genetic locus, RBFOX1, associated with brain amyloidosis, in addition to APOE. It suggests RBFOX1 may be involved in the pathogenesis of Alzheimer's disease, but it does not show any treatment, cure or prevention.
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After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11).
Why it matters
In this trial of 108 patients, bupropion did not significantly reduce apathy compared with placebo in people with Alzheimer's disease. On secondary outcomes, the placebo group showed greater improvement in total neuropsychiatric symptoms and health-related quality of life.
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In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year.
Why it matters
This review of 33 studies with 3,935 participants assessed the accuracy of structural MRI for early diagnosis of Alzheimer's disease dementia in people with mild cognitive impairment, finding no difference in total hippocampal volume accuracy by follow-up duration or age. It addresses diagnostic accuracy only, not treatment, cure, or prevention.
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We evaluated the performance of CSF biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients with cognitive symptoms.
Why it matters
This study measured amyloid-beta 42, total tau and phosphorylated tau in cerebrospinal fluid using Elecsys immunoassays to predict who would decline or develop dementia. It is about predicting risk with biomarkers, not about treating, curing or preventing Alzheimer's disease.
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These two conclusions support a dynamic biomarker model in which Alzheimer's disease is characterized first by the appearance of amyloidosis and later by tauopathy, with tauopathy being the proteinopathy associated with clinical symptoms.
Why it matters
This work supports a model in which amyloid appears first and tauopathy later, with tauopathy linked to clinical symptoms. It describes the sequence of brain changes in Alzheimer's disease and does not offer a treatment, cure, or prevention.
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The mean (SD) age of the 842 participants in cohort 1 was 72 (5.6) years, with a range of 59 to 88 years, and 446 (52.5%) were female.
Why it matters
In 842 adults aged 59–88 (average 72, 52.5% women), including people with and without cognitive impairment, researchers tested fully automated blood assays as screening tests for Alzheimer's-related β-amyloid. Combined with APOE gene type, the tests reached an accuracy score (AUC) of 0.85 (95% CI 0.82–0.88), and the results were "similar in CU and cognitively impaired participants, and in younger and older participants." This is a screening-accuracy result for amyloid status, not a dementia diagnosis or a treatment, and the record we hold does not report how the blood tests did without APOE.
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Among Aβ-positive individuals, greater CR related to attenuated clinical progression in predementia stages of AD, but accelerated cognitive decline after the onset of dementia.
Why it matters
In amyloid-positive participants, greater cognitive reserve based on gray matter volume was linked to lower risk of progressing to mild cognitive impairment or Alzheimer's dementia. However, once symptoms appeared, higher cognitive reserve was also associated with faster subsequent decline, so its role in progression is complex.
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Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension.
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In secondary analyses, the area under the curve (AUC) of [18F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [18F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined.
Why it matters
This study found that [18F]flortaucipir PET could discriminate Alzheimer disease from other neurodegenerative diseases in patients with established diagnoses at a memory disorder clinic. It is a diagnostic accuracy study, not a treatment, cure or prevention for Alzheimer's disease.
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The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds.
Why it matters
In this population sample of 70-year-olds, the prevalence of preclinical Alzheimer disease varied widely depending on which classification system was used. The authors state that the clinical implications of these findings need to be scrutinized further in longitudinal studies.
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Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits.
Why it matters
In a randomized, double-blind trial, 42 patients with mild Alzheimer's disease received active or sham deep brain stimulation directed at the fornix, with cognitive function and cerebral glucose metabolism measured up to 12 months after implantation. This was a Phase II study testing safety and efficacy of a treatment, and it does not report a cure or prevention.
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The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field.
Why it matters
This genome-wide interaction study in 678 Alzheimer's Disease Neuroimaging Initiative participants looked for genetic factors that modify the relationship between brain beta-amyloid burden and cognitive impairment. The authors note that beta-amyloid is necessary for the pathologic diagnosis of Alzheimer's disease but is not sufficient to cause dementia.
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Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology.
Why it matters
In this pilot trial of 39 patients with Alzheimer disease, omega-3 fatty acids alone or with alpha lipoic acid did not significantly differ from placebo on the primary measure of peripheral F2-isoprostane levels or on ADAS-cog and ADL scores. The omega-3 plus alpha lipoic acid group showed less decline on the Mini-Mental State Examination and IADL, and the omega-3 group showed less decline on IADL, but these were secondary measures in a small pilot study.
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71/100
There was no difference between groups in time to emergence of agitation or psychosis (Cox proportional hazard ratio, 0.96; P = .88).
Why it matters
In this trial, valproate did not delay or prevent the emergence of agitation or psychosis in people with moderate Alzheimer disease. This means valproate was not effective for preventing these symptoms.
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71/100
(18)F-Flutemetamol performs similarly to the (11)C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.
Why it matters
In this small phase 2 study, blinded readers rated flutemetamol PET scans as showing raised amyloid in "25 of 27 scans from AD subjects and 1 of 15 scans from the elderly" healthy volunteers. Against clinical diagnosis, that gave a sensitivity of 93.1% and a specificity of 93.3%. Its uptake values correlated closely with the established tracer PIB in the same people (r 0.89–0.92), and repeat scans in 5 patients varied by 1–4%. The authors say it "performs similarly" to PIB and, unlike PIB, does not need "an on-site cyclotron", but the study does not report a visual-read result for its 20 MCI patients and did not check scans against brain tissue.
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Sertraline did not demonstrate efficacy for the treatment depression symptoms in patients with AD.
Why it matters
In this trial, sertraline did not differ from placebo on measures of depression in people with Alzheimer disease, and its use was linked to more adverse events. This means sertraline was not shown to effectively treat depression in this population.
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In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.
Why it matters
Over an average 5.4 years of follow-up, people with high adherence to a Mediterranean-type diet and those doing much physical activity each had a lower risk of Alzheimer's (hazard ratios 0.60 and 0.67), independently of each other. People who did both had an absolute risk of 12%, compared with 19% for those who did neither. These are observational associations, but they point to diet and exercise as separate possible levers for prevention.
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Alzheimer's disease is the most common form of dementia.
Why it matters
This meta-analysis found that shrinkage in the entorhinal area and hippocampus, and reduced metabolism in certain parietal regions, were the most reliable imaging signs for predicting progression from mild cognitive impairment to Alzheimer's disease. These markers may aid early diagnosis, but the study does not provide a treatment.
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Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD).
Why it matters
In this cohort of patients with Alzheimer's disease, an episode of delirium was followed by a significant acceleration in cognitive decline, with decline occurring about three times faster than in those without delirium. This suggests that preventing or managing delirium may help slow decline, but it does not show a cure or prevention for Alzheimer's disease.
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.
- Cognitive and neurobiologic markers of early Alzheimer disease
- ApoE influences regional white-matter axonal density loss in Alzheimer's disease
- Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds
- Sex differences in plasma p-tau181 associations with Alzheimer's disease biomarkers, cognitive decline, and clinical progression
- Association of residential neighborhood disadvantage with amyloid PET positivity among cognitively impaired individuals
- Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer’s disease
- Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals
- Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies
- Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis
- Argentina-Alzheimer's Disease Neuroimaging Initiative: pioneering Alzheimer's Research in Latin America and its Implications for Regional Advancement