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.
-
74/100
Patients' mean age was 73.6 years (range 48 to 92 years).
Why it matters
In this 24-week randomized trial, donepezil produced benefits on a global measure of change compared with placebo in patients with moderate to severe Alzheimer's disease. This shows a symptomatic benefit in more advanced disease, not a cure or prevention.
-
74/100
Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD.
Why it matters
In this randomized, double-blind, placebo-controlled trial of 42 women with mild-to-moderate Alzheimer's disease dementia, short-term conjugated equine estrogens showed no significant differences or statistical trends versus placebo on the primary cognitive outcome, clinician-rated global impression of change, or caregiver-rated functional status. The authors conclude that short-term estrogen therapy does not improve symptoms of most women with Alzheimer's disease, while noting the small sample size limits conclusions.
-
Furthermore, the dramatic and favorable effects on disturbing behaviors in AD suggest a novel approach for treatment of noncognitive symptoms.
Why it matters
In this 6-month trial of 343 patients with mild to moderate Alzheimer disease, the high dose of xanomeline produced a significant treatment effect on cognition compared with placebo, and the authors report favorable effects on disturbing behaviors. This provides evidence that a direct-acting muscarinic receptor agonist can improve cognitive function in patients with Alzheimer disease.
-
Triggering receptor expressed on myeloid cells 2 (TREM2) regulates microglial function and is implicated in Alzheimer's disease (AD) pathogenesis.
Why it matters
In this phase 2 trial of 381 participants with early Alzheimer's disease, the TREM2 agonistic antibody AL002 did not meet the primary endpoint of change in the Clinical Dementia Rating-Sum of Boxes score versus placebo, although it showed target engagement in the central nervous system. The most frequent treatment-emergent adverse events were MRI changes resembling amyloid-related imaging abnormalities, so this treatment was negative for clinical benefit in this trial.
-
The panel cautions users of this guideline that there is significant variability in diagnostic test accuracy and many commercially available BBM tests do not meet these thresholds, especially using a single cutoff.
Why it matters
This clinical practice guideline cautions that there is significant variability in the accuracy of blood-based biomarker tests for Alzheimer's disease. It notes that many commercially available tests do not meet the guideline's thresholds, especially when using a single cutoff.
-
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.
Why it matters
By analyzing cerebrospinal fluid proteins across the Alzheimer's disease continuum, this study identified over 2,000 proteins that are dysregulated and grouped them into stages involving processes like neuronal death, microglial changes, and brain plasticity. Machine learning models built from these proteins predicted Alzheimer's biomarker status and clinical status with high accuracy and could identify people who would later convert to Alzheimer's disease.
-
The mean (SD) baseline age of 758 participants was 61.5 (6.1) years, and 424 participants [55.9%] were female.
Why it matters
Among 758 people with type 2 diabetes and overweight or obesity, rising plasma NfL and GFAP levels over time were associated with cognitive decline, while Aβ42/40 and pTau-181 were not. This is an observational biomarker study and does not test any treatment or prevention for Alzheimer's disease.
-
Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected.
Why it matters
Pooling 21 observational studies (65,955 older adults), this pre-registered meta-analysis found that closer adherence to a Mediterranean diet was linked to modestly lower odds of dementia (OR 0.89) and somewhat lower odds of Alzheimer disease (OR 0.73). The authors describe the risk reduction as "relatively low", and results varied considerably between studies. Because the included studies were observational, this shows an association, not that the diet prevents dementia.
-
Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively).
Why it matters
In memory clinic patients, having amyloid PET early in the diagnostic workup led far more people to receive an etiological diagnosis with very high confidence after 3 months than having it later. This is about improving diagnosis, not about treating, curing or preventing Alzheimer's disease.
-
73/100
In this exploratory analysis, the APOE ε3[R145C] missense variant was associated with an increased risk of AD among individuals of African ancestry with the ε3/ε4 genotype.
Why it matters
In 2,888 people with Alzheimer's and 4,957 controls of African ancestry, those with the ε3/ε4 APOE genotype who also carried a variant called R145C had about 3 times the odds of Alzheimer's (odds ratio 3.01) and a reported onset about 6 years earlier. The link was not seen in other APOE genotypes, and a second variant, R150H, showed no association. The authors call this exploratory and say external validation is needed before it could inform genetic risk assessment for people of African ancestry.
-
Pooling 29 studies and over 2 million people, this meta-analysis found that people who were more physically active, especially at moderate-to-vigorous intensity, had a notably lower risk of developing Alzheimer's disease, though the protective association was stronger in studies with shorter follow-up periods.
Why it matters
Pooling 29 studies, more physically active people had a lower risk of Alzheimer's disease, with the strongest link for high-intensity activity. However, the protective association weakened in studies with more than 15 years of follow-up, which the authors note is consistent with possible reverse causation.
-
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis.
Why it matters
In the largest combined genetics study of spinal-fluid Alzheimer's markers (31 cohorts, 13,116 people), researchers found that, besides APOE, a variant region near CR1 was linked to amyloid-beta 42 levels, and regions near BIN1, GMNC and C16orf95 were linked to phosphorylated tau; C16orf95 had not been reported before. Grouping all known Alzheimer's risk genes by their effect on these markers gave four clusters, suggesting several separate biological routes into the disease. GMNC and C16orf95 were also linked to the size of the brain's fluid-filled ventricles, hinting that tau levels and brain structure share some genetic roots. These are associations, not a test or a treatment.
-
Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo.
Why it matters
In this trial of 200 patients with Alzheimer disease, methylphenidate produced a larger decrease in apathy scores than placebo over 6 months, with no significant differences in cognitive measures, quality of life, or safety profile between groups. This supports methylphenidate for treating apathy as a symptom, not for curing or preventing Alzheimer's disease.
-
change from baseline in Preclinical Alzheimer Cognitive Composite score.
Why it matters
In 557 people with preclinical Alzheimer disease, atabecestat 25 mg was linked to worse thinking scores than placebo by month 6, and the authors report worsening as early as 3 months along with neuropsychiatric side effects. Dosing was stopped early in May 2018 because of liver-related adverse events; after 6 months off the drug there was "evidence of reversibility." The trial gives no sign of benefit and documents early harm from this drug.
-
Of 157 participants initially assessed, 137 were enrolled in the Age-Well clinical trial, and 127 were analyzed in this study.
Why it matters
This secondary analysis of a randomized clinical trial examined which brain changes, including amyloid deposition, gray matter volume, perfusion, and glucose metabolism, are associated with sleep-disordered breathing in cognitively unimpaired older adults. The authors say the results support screening and treating sleep-disordered breathing to reduce Alzheimer disease risk, but this cross-sectional analysis cannot show that treatment prevents the disease.
-
The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.
Why it matters
This paper describes Version 3 of a standardized data set used by US Alzheimer's Disease Centers, updated to match current consensus diagnostic criteria, with 4820 participants enrolled using it between 2015 and 2018. It shows that many research institutions can collaborate over a decade to produce and use standardized data collection instruments, which supports research rather than being a treatment or cure.
-
73/100
Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.
Why it matters
Several cerebrospinal fluid markers of neuroinflammation and cerebrovascular dysfunction were increased across preclinical, prodromal, and dementia stages of Alzheimer's disease and were linked to tau markers and cortical thinning. These markers may help track disease processes, but the study does not show that targeting them treats or prevents Alzheimer's disease.
-
We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages.
Why it matters
In brain tissue and blood samples, certain sphingolipid species were associated with severity of Alzheimer pathology at autopsy and with increased risk of future conversion to Alzheimer disease in cognitively normal individuals. The study notes its relatively small number of brain tissue samples as a limitation.
-
Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women.
Why it matters
In 445 cognitively normal older adults followed for a median of 3.1 years in the ADNI study, the 202 with elevated brain amyloid on PET or spinal-fluid testing scored on average 1.51 points lower (95% CI 0.94–2.10) at 4 years on the PACC thinking-test composite than the 243 with normal amyloid. The authors call these analyses exploratory and say the differences are "of uncertain clinical significance", so the study shows an association with later decline, not that amyloid causes it or that any one person will develop dementia.
-
Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity.
Why it matters
This review discusses cholinesterase inhibitors, including rivastigmine, which work by delaying the breakdown of acetylcholine to ease Alzheimer's symptoms. It addresses symptom management rather than curing or preventing the disease, and the provided findings do not report specific results.
-
73/100
An intensive and long-term exercise program had beneficial effects on the physical functioning of patients with AD without increasing the total costs of health and social services or causing any significant adverse effects.
Why it matters
In a one-year randomized trial of 210 people with Alzheimer disease living at home with a spouse, everyone's daily functioning declined, but less with twice-weekly exercise: on the Functional Independence Measure scores fell 7.1 points with home exercise and 10.3 with group exercise, compared with 14.4 with usual care. The exercise groups also had significantly fewer falls, and total care costs were not higher (only the group programme's lower cost, $22,066 vs $34,121 per couple per year, was statistically significant). The trial measured physical function, not memory, and it showed slower decline, not prevention of decline.
-
These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years.
Why it matters
During the first two years of this prevention trial, more cases of Alzheimer disease appeared in the groups assigned to naproxen or celecoxib than in the placebo group, and increased risk remained notable in the first 2.5 years of observations. Later analyses suggested reduced incidence among asymptomatic enrollees given naproxen, but these were secondary analyses.
-
In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.
Why it matters
In 129 people with amnestic mild cognitive impairment, only ventricular and hippocampal volumes predicted progression to Alzheimer's disease, with hippocampal volumes alone giving maximal predictive accuracy of 60.4% among MRI measures. This concerns prediction of progression and does not test any treatment, cure, or prevention.
-
Of 1018 study patients enrolled, 508 were randomly assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12]; p=0.225).
Why it matters
In a double-blind trial of 1,018 people with mild cognitive impairment followed for up to four years, 17.3% of those on rivastigmine and 21.4% on placebo were diagnosed with Alzheimer's disease. The difference was not statistically significant (hazard ratio 0.85, 95% CI 0.64–1.12), and cognitive test scores did not differ either. The authors found no significant safety concerns. They also noted that far fewer participants progressed to Alzheimer's than predicted.
-
73/100
These results support the safety and efficacy of memantine for the treatment of mild to moderate AD.
Why it matters
In this 24-week randomized trial of 403 patients with mild to moderate Alzheimer disease, memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior. Most participants completed the trial.
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.
- Etiology, risk factors, treatments and current status of Alzheimer's disease in Mexico
- Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults
- Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease
- Mosaic Loss of Chromosome Y and Plasma Aβ42/p‐tau181 Ratio as Biomarkers for Alzheimer's Disease in the Midwestern Amish
- Detecting depression in Alzheimer's disease: evaluation of four different scales
- Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer's disease
- Imaging beta-amyloid burden in aging and dementia
- Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease
- Nanoencapsulated Curcumin: Enhanced Efficacy in Reversing Memory Loss in An Alzheimer Disease Model
- Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease