Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Download bibliography of all 5,209 studies, highest score first: BibTeX (.bib) · RIS (.ris)
Highest usefulness score first. Studies without a score come last.
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Longitudinal clinicopathologic cohort study.
Why it matters
At autopsy, 97 members of the Religious Orders Study (44 with clinically diagnosed Alzheimer's, 53 without dementia) who had been tested about 8 months before death showed that each 1% increase in amyloid load was linked to about 50% higher odds of clinical Alzheimer's, and each additional tangle to more than 20% higher odds, in separate analyses. The authors conclude this is "consistent with a sequence" in which amyloid's effect on clinical disease works through tangles. The study is an observational autopsy comparison that does not show cause and effect or test any treatment.
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Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders.
Why it matters
This 2003 study compared spinal-fluid tau and amyloid-beta 42 measured during life with diagnoses confirmed later, and found average tau of 612 pg/mL in Alzheimer's versus 140 pg/mL in cognitively normal controls, with lower levels in frontal (272) and Lewy-body (282) dementia. The authors conclude that raised tau "can help discriminate AD from other dementing disorders," but 20 of the 74 Alzheimer's patients had tau below 334 pg/mL, so a normal result did not rule the disease out. Low amyloid-beta 42 separated Alzheimer's from frontal dementia and controls, but not from Lewy-body or prion disease.
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Early diagnosis of Alzheimer's disease (AD) is needed to initiate symptomatic treatment with acetylcholinesterase inhibitors, and will be of even greater significance if drugs aimed at slowing down the degenerative process, such as vaccination regimes and beta-secretase and gamma-secretase inhibitors, prove to affect AD pathology and to have clinical effect.
Why it matters
This 2003 review starts from a clinical problem: doctors had no way to tell which people with mild cognitive impairment would go on to Alzheimer's dementia and which had a "benign" form. It names three spinal-fluid markers (total tau, phosphorylated tau and amyloid-beta 42) that "may, if put in the right clinical context," prove accurate enough to spot early Alzheimer's in these patients. It is a review with no new data and reports no accuracy figures, so it describes a promising approach rather than a proven test.
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The extent to which cerebral atrophy in Alzheimer's disease changes with time is unknown.
Why it matters
This longitudinal MRI study of 12 patients with early-onset Alzheimer's disease found that yearly percentage loss of brain volume increased over time. It describes how brain atrophy progresses and does not test any treatment, cure, or prevention.
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Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about the age of 44.6 years and then declines.
Why it matters
This cross-sectional MRI study assessed frontal lobe white matter integrity in healthy adults and patients with Alzheimer's disease, relating it to brain aging. It is an imaging study and does not test any treatment, cure, or prevention.
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Apolipoprotein E epsilon4 led to increased risk of AD among white subjects but not black subjects.
Why it matters
In this population-based study, the APOE ε4 allele was associated with a 2.73-fold increase in Alzheimer disease risk among white participants but no increase in risk among black participants. This describes a difference in the effect of a genetic risk factor between races and does not test any treatment, cure, or prevention.
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Our results indicate that altered tau and Abeta42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.
Why it matters
In 28 people with mild cognitive impairment followed for 18 months, higher cerebrospinal fluid tau and lower beta-amyloid 42 at baseline were found in those who progressed to probable Alzheimer's disease compared with those who remained stable. This is a small longitudinal biomarker study and does not show that any treatment, cure, or prevention works.
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Cerebrolysin (Cere) is a compound with neurotrophic activity.
Why it matters
In this trial of 192 patients, those given Cerebrolysin showed a significant difference on a global rating scale at week 12 in favor of the treatment, and the authors report significant improvements in the global score two months after active treatment ended. The groups differed significantly at baseline in age, age of dementia onset, and number of patients with hallucinations, which limits how the results can be interpreted.
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Why it matters
Reports that a subset of NSAIDs lower amyloid-forming Aβ42 independently of cyclooxygenase activity.
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Hippocampal atrophy is not specific for AD but is also seen in semantic dementia.
Why it matters
This study characterized patterns of temporal lobe atrophy in Alzheimer's disease versus semantic dementia and related them to cognitive profiles. It has implications for diagnosis and understanding cognitive deficits, but does not test any treatment, cure or prevention.
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The Alzheimer type of dementia and stroke are known to increase at comparable rates with age.
Why it matters
This review reports that vascular risk factors such as atherosclerosis, atrial fibrillation, coronary artery disease, high blood pressure, and diabetes are linked to a higher risk of developing Alzheimer's disease, and that strokes worsen cognitive decline in people who have it. It raises the question of whether reduced blood flow to the brain could be a cause of Alzheimer's disease but does not answer it.
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57/100
Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD).
Why it matters
In this 1999 Nature study, PDAPP mice — engineered to carry a mutant human APP gene and to develop "many of the neuropathological hallmarks of Alzheimer's disease" — were immunized with the Abeta42 peptide either at 6 weeks of age, before pathology began, or at 11 months, when it was "well established". The study reports that immunization "attenuates Alzheimer-disease-like pathology"; our record does not include how large the effect was, which changes were measured, or any effect on memory. These were mice only, so the result says nothing directly about whether this works, or is safe, in people.
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57/100
This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria.
Why it matters
In 134 patients who came to autopsy, clinical diagnosis of probable Alzheimer's disease was correct in 83% of cases and overall clinical accuracy was 75%, but most cases had additional brain findings besides Alzheimer's disease. This concerns diagnostic accuracy only and says nothing about treating, curing or preventing the disease.
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The distribution and density of neurofibrillary tangles and amyloid plaques was studied in a unique series of cases whose premortem cognitive status had been assessed with the Clinical Dementia Rating (CDR), including 39 nondemented cases (CDR = 0; age, 51-88 years), 15 very mildly demented cases (CDR = 0.5), and 8 severely demented (CDR = 3) cases.
Why it matters
This study of brain tissue found that tangles were present in all nondemented cases and increased with age, while plaques were absent in some brains up to age 88. It proposes that some nondemented cases with widely distributed plaques and increased tangles may represent preclinical Alzheimer's disease.
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In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy.
Why it matters
This community survey in rural India found an overall prevalence rate of 0.84% for all dementias in the population aged 55 years and older, and 0.62% for Alzheimer's disease. It also found that greater age was significantly associated with higher prevalence.
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A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals.
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in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female.
Why it matters
This projection suggests that interventions able to delay the onset of Alzheimer's disease by even 1 or 2 years could substantially reduce the number of people living with the disease over the coming decades. It does not test any treatment, but shows the potential public health value of prevention or delay strategies.
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Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity.
Why it matters
In 126 cognitively normal older adults and 94 people with probable Alzheimer's disease, this 1997 MRI study found that the hippocampus, parahippocampal gyrus and amygdala were all smaller in Alzheimer's (p < 0.001). Hippocampal volume separated the groups best, and it was already 1.75 standard deviations below the control average at the very mildest stage (CDR 0.5), compared with 2.22 at the moderate stage. These are group averages, and hippocampal volume also shrank with age in healthy people, so the study does not show how accurate a single person's scan is; no treatment was tested.
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This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.
Why it matters
In a nested case-control study of women from a Southern California retirement community, those who had used estrogen were less likely to have Alzheimer's or related dementia recorded on their death certificate (odds ratio 0.65, 95% CI 0.49–0.88). For oral conjugated equine estrogen, the odds fell further with higher doses and longer use (both P = .01). This is an observed association, not proof that estrogen prevents Alzheimer's; the authors concluded only that it "may be useful for preventing or delaying" the disease.
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In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease.
Why it matters
In 11 cognitively normal people aged 50–65 who carried two copies of the APOE ε4 gene variant and had a family history of Alzheimer's, PET scans showed lower glucose use in the same posterior cingulate, parietal, temporal and prefrontal regions previously seen to decline in patients with probable Alzheimer's, compared with 22 matched non-carriers. The authors read this as "preclinical evidence" that ε4 is a risk factor, and suggested PET "may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease". It is a small group comparison of brain metabolism: it doesn't show who goes on to develop dementia, and it doesn't test any treatment.
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The protease inhibitor alpha 1-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposits of Alzheimer's disease.
Why it matters
Alpha 1-antichymotrypsin and apolipoprotein E are both found inside Alzheimer's plaques alongside amyloid-beta, and in this test-tube study adding either one to amyloid-beta increased filament formation 10- to 20-fold, with apoE4 — the form linked to late-onset Alzheimer's — the most active. The authors suggest that plaques form when such "amyloid-promoting factors (pathological chaperones)" push amyloid-beta into filaments in certain brain regions. No people or animals were studied and no treatment was tested, so the findings show what these proteins can do in a test tube, not how much they drive the disease.
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Why it matters
Reports a protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.
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57/100
The amyloid beta protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer's disease and Down syndrome.
Why it matters
This 1987 lab study isolated a DNA copy of the gene for amyloid beta, a main component of the plaques and blood-vessel amyloid seen in Alzheimer's disease and Down syndrome. The authors report that this suggests the protein comes from a larger protein made in many tissues, and that the gene sits on chromosome 21, which could explain why it was over-expressed in brain tissue from fetuses with Down syndrome (who carry an extra copy of that chromosome). Mapping placed the gene near the genetic defect behind inherited Alzheimer's (near, not shown to be that defect), and the study tested no treatment or prevention.
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Previously derived polygenic risk scores (PRSs) for Alzheimer's disease (AD) perform inconsistently across diverse ancestries.
Why it matters
A polygenic risk score built for multiple ancestries was linked to Alzheimer's diagnosis, worse memory and thinking, and more disease-related brain changes. This is a risk-stratification tool, not a way to treat, cure or prevent the disease.
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The APOE locus is the strongest genetic factor for Alzheimer's disease, with ε4 increasing and ε2 decreasing risk, yet the basis of these opposing effects remains unclear.
Why it matters
This proteomic study found that APOE ε2 and ε4 appear to affect Alzheimer's risk through different molecular pathways. It identifies candidate biomarkers and targets for allele-specific interventions, but no treatment is tested.
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.
- Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia
- Reasons for seeking genetic susceptibility testing among first-degree relatives of people with Alzheimer disease
- Conformation and fibrillogenesis of Alzheimer A beta peptides with selected substitution of charged residues
- Cerebral Amyloid Angiopathy and Downstream Alzheimer Disease Plasma Biomarkers
- Amyloid angiopathy-related vascular cognitive impairment
- Evaluation of Disease Severity Using CSF Biomarkers in Patients With Probable Cerebral Amyloid Angiopathy
- Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain
- Current and evolving treatment strategies for the Alzheimer disease continuum
- Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience
- Why looking at the whole hippocampus is not enough-a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer's disease diagnosis