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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In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
Why it matters
Among 172 autopsied cases with REM sleep behavior disorder, 94% of those with a neurodegenerative disorder had a synucleinopathy, and in about half the RBD preceded cognitive impairment, parkinsonism, or autonomic dysfunction. This describes pathology and timing of disease onset, not a treatment, cure, or prevention for Alzheimer's disease.
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Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are devastating neurodegenerative disorders with clinical, genetic, and neuropathological overlap.
Why it matters
In brain tissue from people with frontotemporal dementia or ALS caused by the C9ORF72 GGGGCC repeat expansion, antibodies made against peptides predicted to come from "unconventional" (RAN) translation of the repeat detected insoluble material and neuronal inclusions throughout the brain and spinal cord. The same antibodies found nothing in other neurodegenerative diseases tested, including CAG repeat disorders, or in patients' tissues outside the nervous system, which the authors call "a potential biomarker" for c9FTD/ALS. This is a post-mortem tissue study of FTD/ALS, not Alzheimer's; no biomarker accuracy was measured and no treatment was tested.
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Our results show that TREM2 is responsible for an unexpectedly high number of dementia cases in our cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded.
Why it matters
Among 44 Turkish patients with a frontotemporal dementia-like illness seen at one Istanbul clinic, gene sequencing found that 3 carried two altered copies of TREM2, a gene previously tied to the bone-and-brain disorder PLOSL. None of the 3 had bone cysts: they "presented with behavioral change and subsequent cognitive impairment and motor features", and brain scans showed white matter changes and frontal shrinkage. The authors suggest TREM2 "should be taken into account when mutations in other dementia genes are excluded"; this is a small single-clinic case series, not a treatment study, and its carrier rate may not apply elsewhere.
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Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism.
Why it matters
In animal experiments, cerebrospinal fluid flowed into brain tissue along spaces around arteries and drained along spaces around veins, carrying away solutes including amyloid β. Animals lacking the water channel aquaporin-4 showed about a 70% reduction in solute clearance, and the authors suggest impairment of this pathway may contribute to the buildup of proteins in neurodegenerative conditions.
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Borderline personality disorder (BPD) is a genetically influenced psychiatric illness with disruptions in neural systems supporting cognition and emotion regulation.
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57/100
Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum.
Why it matters
In 95 pathologically confirmed cases of frontotemporal lobar degeneration, this study related clinical, neuropsychological, and neuroimaging features to tissue pathology, finding certain relatively specific clinicopathological associations. It is a retrospective analysis and does not test any treatment.
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The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD).
Why it matters
Forty-five patients with Alzheimer's disease were randomly assigned to real repetitive transcranial magnetic stimulation at 20 Hz or 1 Hz over the dorsolateral prefrontal cortex, or to sham stimulation, given once daily for five consecutive days. The study compared effects on cognitive function and cortical excitability, and it does not report a cure or prevention.
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Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF.
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Furthermore, the CSF biomarker analyses provide a first insight into the potentially predominant pathogenetic mechanism(s) underlying the association between AD risk and PICALM.
Why it matters
Two earlier genome-wide studies flagged the genes CLU, CR1 and PICALM as possible Alzheimer risk genes, but the signals had not been confirmed in other settings. This study tested 5 variants in 4,254 people of European descent — US families with several affected members and a German case-control group — and found that all three genes were significantly associated with Alzheimer risk. The authors call this "compelling independent evidence" of a genetic link; it shows an association with risk, not a cause, a test or a treatment.
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Donepezil may effectively and safely improve overall functioning of DS patients with severe cognitive impairment.
Why it matters
In this 24-week trial of 21 people with Down syndrome and severe cognitive impairment, those given donepezil showed significantly better scores on a measure of daily functioning than those given placebo, with no adverse effects reported. The authors conclude donepezil may effectively and safely improve overall functioning in this group, though the small number of participants means the findings are preliminary.
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The study of patients with semantic dementia, a variant of frontotemporal lobar degeneration, has emerged over the last two decades as an important lesion model for studying human semantic memory.
Why it matters
In patients with semantic dementia, reduced metabolism in the anterior fusiform region was the strongest predictor of semantic memory scores. This is about how the brain relates to memory loss, not about treating or preventing dementia.
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Abnormal intracellular protein aggregates comprise a key characteristic in most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
This review describes how clumps of the proteins TDP-43 and FUS are found in ALS and frontotemporal dementia, leading to a new way of classifying these diseases. It notes that the mechanisms causing these protein clumps and the resulting nerve damage are still unknown, though these proteins are seen as promising candidates for future biomarker tests and targeted therapies.
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57/100
These cases illustrate that the alpha-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA.
Why it matters
Acting out dreams during sleep (REM sleep behavior disorder) appeared up to 50 years (median 25) before Parkinson's disease, dementia with Lewy bodies or multiple system atrophy in 27 Mayo Clinic patients, and 63% of them eventually developed dementia. The authors say this suggests the alpha-synuclein disease process "may start decades before the first symptoms." Every patient was chosen because they had already developed one of these conditions, so the study cannot say how likely someone with this sleep disorder is to develop one.
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Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.
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Our findings suggest that APOE epsilon4-mediated risk for Alzheimer disease is associated with widespread decline in rCBF over time that precedes the onset of dementia.
Why it matters
In nondemented older adults, APOE epsilon4 carriers showed greater decline in regional cerebral blood flow over 8 years than noncarriers, in brain regions vulnerable to Alzheimer disease. This suggests that APOE epsilon4-related risk involves widespread decline in brain blood flow that precedes dementia, though the study did not test any treatment.
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Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD).
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To what degree does the so-called 'initial hit' of the brain versus chronic epilepsy contribute towards the memory impairment observed in chronic temporal lobe epilepsy (TLE) patients?
Why it matters
This study examined memory in people with chronic temporal lobe epilepsy compared with healthy controls, not Alzheimer's disease. It provides no information about treating, curing or preventing Alzheimer's disease.
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Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes.
Why it matters
This study mapped regions of chromosome 21 linked to various Down syndrome features, including DS-Alzheimer disease, using genetic data from 30 people with rare partial trisomies. It provides evidence against some proposed genetic explanations but does not offer a treatment or prevention for Alzheimer's disease.
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This study investigated amyotrophic lateral sclerosis, an adult-onset neurological disorder that leads to the degeneration of motor neurons and involves TDP-43 as a key component of ubiquitinated aggregates.
Why it matters
Reports mutations in the TARDBP gene in people with sporadic and familial amyotrophic lateral sclerosis. It is not a study of Alzheimer's disease or dementia.
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Although olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population.
Why it matters
This study found that impaired olfaction can predate clinical Parkinson's disease in men by at least 4 years and may help screen for those at high risk. It concerns Parkinson's disease, not Alzheimer's disease, and reports no treatment, cure, or prevention.
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We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects > or =65 years, using any of three models.
Why it matters
Using a large US Veterans Affairs database, this study found that simvastatin was associated with a significant reduction in the incidence of dementia in subjects aged 65 or older. It examined associations between different statins and dementia rather than testing a treatment directly.
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57/100
Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), which are widely presumed to cause the disease.
Why it matters
In mice engineered to make human amyloid precursor protein, reducing the mice's own tau prevented behavioral deficits without changing their high amyloid-beta levels. Tau reduction also protected mice against excitotoxicity, and the authors suggest it may represent an effective strategy for treating Alzheimer's disease.
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Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1, PS2) increase production of beta-amyloid 42 (Abeta42) and cause familial Alzheimer's disease (FAD).
Why it matters
This is a study in transgenic mice, not people, so any implications for treating or preventing Alzheimer's disease in humans are preliminary. It describes a mouse model that rapidly develops amyloid plaques and neuron loss, which may help researchers study the disease process but does not itself demonstrate a treatment or cure.
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Different duplications of the APP locus have been identified in five families with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta-related cerebral amyloid angiopathy (CAA).
Why it matters
This study describes the phenotype associated with APP duplication in five families with autosomal dominant early onset Alzheimer's disease and Abeta-related cerebral amyloid angiopathy, finding dementia in all cases. It is descriptive research on a genetic form of disease and does not provide a treatment, cure, or prevention.
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Specific alleles of the DISC1 and TRAX genes on 1q42 appear to contribute to genetic risk for schizophrenia through disruptive effects on the structure and function of the prefrontal cortex, medial temporal lobe, and other brain regions.
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.
- Xixin Decoction’s novel mechanism for alleviating Alzheimer’s disease cognitive dysfunction by modulating amyloid-β transport across the blood–brain barrier to reduce neuroinflammation
- The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex
- SnapShot: Genetics of ALS and FTD
- Cerebrospinal fluid YKL‐40 relates to white matter hyperintensity progression in females but not males over a 6‐year period
- Biochemical staging of synucleinopathy and amyloid deposition in dementia with Lewy bodies
- A Review of the Molecular Mechanisms of Traumatic Brain Injury
- Protective and damaging effects of stress mediators: central role of the brain
- Immediate improvement of speech-in-noise perception through multisensory stimulation via an auditory to tactile sensory substitution
- Vasculocentric Axonal NfH in Small Vessel Disease
- Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment