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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HRT introduction is associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only.
Why it matters
In the EPAD cohort, APOE4 women who used hormone replacement therapy had the highest delayed memory scores and larger entorhinal and amygdala volumes compared with non-users and non-carriers. Earlier introduction of HRT was associated with larger brain volumes.
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The role of microglia in tau accumulation is currently unclear but could provide an important insight into the mechanisms underlying Alzheimer's disease (AD) 1 .
Why it matters
In a Swedish cohort of people without dementia, those with Alzheimer's-type amyloid on PET (121) who had higher soluble TREM2, a microglial marker, showed slower amyloid build-up. In those who also had tau on PET (64), higher TREM2 and several related microglial markers went with slower tau accumulation and/or slower cognitive decline. These are associations from observational data. No treatment was tested, and the study does not show that boosting microglia slows Alzheimer's.
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ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased CSF levels of anti-Aβ autoantibodies.
Why it matters
In a longitudinal case series of patients with cerebral amyloid angiopathy-related inflammation, focal peaks of microglial activation colocalized with ARIA-E, and severity was greater in those with both Alzheimer disease and severe cerebral amyloid angiopathy. This concerns the mechanisms of a rare autoimmune encephalopathy and a side effect seen with amyloid-lowering antibodies, not a treatment, cure or prevention for Alzheimer's disease.
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We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status.
Why it matters
Greater white matter hyperintensity volume was associated with older age and current smoking, and greater white matter injury in black participants became nonsignificant after adjusting for cardiovascular risk factors and socioeconomic status. The study was cross-sectional and looked at brain imaging, not dementia treatment or prevention.
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MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors.
Why it matters
In this early phase 1 trial of only five patients, opening the blood-brain barrier with focused ultrasound was feasible and reversible with no serious side effects. The study is still in progress and reports descriptive results, so it does not yet show any treatment benefit.
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MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism.
Why it matters
In this trial, no significant effect of the multidomain intervention was observed on the primary brain glucose metabolism outcome at 6 months. An exploratory analysis suggested a difference in favor of the intervention in some brain regions, but this is preliminary and the overall result was not significant.
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Combined low plasma Aβ 42 /Aβ 40 ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function.
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Several clinical trials are planned for familial forms of frontotemporal lobar degeneration (f-FTLD).
Why it matters
This study characterized where and how fast brain atrophy occurs in three genetic forms of familial frontotemporal dementia, across all stages from no symptoms to dementia. This information could help design future clinical trials by improving the ability to detect treatment effects.
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We included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [ 18 F]florbetapir PET and CSF Aβ 42 available.
Why it matters
This longitudinal ADNI study of 730 participants without dementia examined whether discordant amyloid PET and CSF biomarkers at baseline relate to tau pathology five years later. It is an observational biomarker study, so it cannot show that any treatment changes this progression.
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Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD).
Why it matters
In people with and without dementia, those who had higher levels of sTREM2 in their spinal fluid (a marker of immune-cell activity in the brain) built up amyloid more slowly on PET scans over about 2 years. In a subset scanned once, they also had lower tau. This links brain immune activity to slower amyloid build-up, but it is an observational association; it does not show that boosting sTREM2 or microglia treats or prevents Alzheimer's.
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Small vessel disease is a disorder of cerebral microvessels that causes white matter hyperintensities and several other common abnormalities (eg, recent small subcortical infarcts and lacunes) seen on brain imaging.
Why it matters
This review describes cerebral small vessel disease, which shows up on brain scans as white matter hyperintensities, small subcortical infarcts and lacunes, as a common cause of stroke and vascular dementia whose underlying cause is still "poorly understood". It summarises human research linking the disease to blood vessel lining (endothelial) problems such as blood-brain barrier dysfunction, impaired blood flow and fluid drainage, inflammation and myelin damage, and says the link between these lesions and symptoms is "highly variable". It reports no new data and names no treatment; which abnormalities can be reversed is listed as an open question.
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Using Fisher's exact test, there was significant association of both ABI3_rs616338-T (OR = 1.41, p = 0.044) and PLCG2_rs72824905-G (OR = 0.56, p = 0.008) with AD.
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The neuroimmune system is involved in development, normal functioning, aging, and injury of the central nervous system.
Why it matters
This review describes how microglia normally sense, support and protect neurons, and how disruption of these functions and dysregulation of neuroinflammation contribute to neuron injury in diseases including Alzheimer's disease. It discusses pathways that may be involved, but offers no proven treatment, cure or prevention.
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In Lewy body diseases-including Parkinson's disease, without or with dementia, dementia with Lewy bodies, and Alzheimer's disease with Lewy body co-pathology 1 -α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites 2 .
Why it matters
Alpha-synuclein clumps taken from multiple system atrophy are more compact than those from Lewy body disease and, in this laboratory work, were about 1,000-fold more potent at seeding new aggregation — a difference the authors call consistent with how aggressive multiple system atrophy is. Neither form preferred one cell type when seeding, yet oligodendrocytes and not neurons converted misfolded alpha-synuclein into the multiple-system-atrophy-like strain, and that strain kept its high seeding activity once in neurons, so the authors conclude strains are set by both the seed and the cell it sits in. This is basic laboratory science: it tests no treatment, measures nothing in patients, and the authors themselves leave open why the diseases differ in which cells are affected.
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An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear.
Why it matters
Using human induced motor neurons, this study found that the expanded C9ORF72 repeat reduced C9ORF72 levels and caused neurodegeneration through glutamate receptor buildup and poor clearance of toxic repeat proteins. Restoring C9ORF72 or boosting RAB5 rescued patient neurons and helped in mouse models, but this remains early laboratory work.
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Animal models of Alzheimer's disease have suggested that tau pathology propagation, facilitated by amyloid pathology, may occur along connected pathways.
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TREM2 is an innate immune receptor expressed on the surface of microglia.
Why it matters
This cross-sectional study, run across several centres, measured soluble TREM2 (sTREM2) in spinal fluid at different stages of Alzheimer's disease, in controls, and in cognitively normal people with suspected non-Alzheimer's pathology. It reports that sTREM2 "levels were higher in mild cognitive impairment due to AD than in all other AD groups and controls." People were measured once, so the study shows a difference between groups, not change over time. It points to a possible marker of brain immune-cell activity, not a diagnostic test or a treatment.
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Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor that recognizes changes in the lipid microenvironment, which may occur during amyloid β (Aβ) accumulation and neuronal degeneration in Alzheimer's disease (AD).
Why it matters
In mouse models, TREM2 deficiency prevented microglial clustering around amyloid-beta deposits, and amyloid-associated myeloid cells came from brain-resident microglia. It is animal work on a mechanism and does not test a treatment or cure.
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Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.
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This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages.
Why it matters
Women with mild cognitive impairment or Alzheimer's disease performed better than men on verbal memory tests even when their hippocampus showed similar shrinkage. This suggests women may have a form of cognitive reserve that delays memory decline, which matters for interpreting test results but offers no treatment or cure.
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The discovery that heterozygous missense mutations in the gene encoding triggering receptor expressed on myeloid cells 2 (TREM2) are risk factors for Alzheimer's disease (AD), with only the apolipoprotein E (APOE) ε4 gene allele conferring a higher risk, has led to increased interest in immune biology in the brain.
Why it matters
The authors found that commercial ELISA kits for soluble TREM2 (sTREM2), a protein shed from the brain's immune cells (microglia), were "unreliable" in their hands. So they developed a mass spectrometry method to measure it in spinal fluid, and used it on samples "from memory clinics in Sweden and the UK". The title reports that sTREM2 is increased in Alzheimer's disease, but our record holds no group sizes, effect size or statistics, so how large or consistent the increase is cannot be checked here. It is a measurement study and does not test any treatment, cure or prevention.
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We used a protein quantitative trait analysis in monocytes from 226 individuals to evaluate cross-talk between Alzheimer loci.
Why it matters
In immune cells (monocytes) taken from the blood of 226 people, this study found that carrying the CD33 Alzheimer risk allele went with greater TREM2 expression, and that suppressing CD33 lowered TREM2. It also reported that the NME8 locus influenced PTK2B, and that cortical TREM2 mRNA was higher with amyloid pathology. These findings link several Alzheimer risk genes to one another, but the study tests no treatment and reports no effect on memory, diagnosis or disease progression.
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Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease.
Why it matters
In this multicenter study, 33.3% of patients with idiopathic REM sleep behavior disorder developed a defined neurodegenerative disease over follow-up, with risk reaching 41% after 5 years. This identifies a high-risk group but does not test any treatment or prevention.
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60/100
Salience network hyperconnectivity may be a distinguishing feature in children with ASD.
Why it matters
In 20 children with autism and 20 matched typically developing children, several large-scale brain networks showed stronger connectivity in autism, and a classifier could distinguish the groups. This concerns autism, not Alzheimer's disease, and offers nothing on treating, curing or preventing Alzheimer's.
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60/100
The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI.
Why it matters
In 31 people with subjective memory impairment and 56 controls, the impaired group showed altered glucose metabolism in the precuneus and medial temporal lobe, reduced right hippocampal volume, and poorer memory at follow-up. This observational study supports the idea that subjective memory impairment may be an early sign of Alzheimer's but does not test any treatment or prevention.
From across this topic
10 of the 4,748 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.
- The substrate repertoire of γ-secretase/presenilin
- Microglial activation and amyloid deposition in mild cognitive impairment: a PET study
- Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease
- Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly
- Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease
- Pyk2 plays a critical role in synaptic dysfunction during the early stages of Alzheimer’s disease
- Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease
- Frontotemporal Lobar degeneration with TDP-43 presenting as progressive supranuclear palsy syndrome
- The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians
- HSPA13 gene and microRNA-155: relationship between Down syndrome and Alzheimer's disease