Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients, which seems to contribute to a more aggressive disease. Our aim was to evaluate cerebrospinal fluid (CSF) amyloid-beta as a predictor of the mortality of FTD patients. We included 99 patients diagnosed with FTD-both behavioral and language variants-with no associated motor neuron disease, from whom a CSF sample was collected. These patients were followed prospectively in our center, and demographic and clinical data were obtained. The survival analysis was carried through a Cox regression model. Patients who died during follow up had a significantly lower CSF amyloid-beta than those who did not. The survival analysis demonstrated that an increased death rate was associated with a lower CSF amyloid-beta (HR = 0.999, 95% CI = [0.997, 1.000], = 0.049). Neither demographic nor clinical variables, nor CSF total tau or p-tau were significantly associated with this endpoint. These results suggest that amyloid deposition in FTD patients may be associated with a higher mortality.
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http://dx.doi.org/10.3390/diagnostics9040162 | DOI Listing |
J Prev Alzheimers Dis
January 2025
Geriatrics Department, Fernand Widal Lariboisière University Hospital, GHU APHP.Nord, Paris, France; Paris-Cité University, Inserm U1144, Paris, France; Paris-Cité University, Inserm U1153, Paris, France.
Background: The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated.
Objectives: To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients.
J Prev Alzheimers Dis
January 2025
CenExel iResearch, Atlanta, GA, USA.
Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.
Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).
Int J Mol Sci
January 2025
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, 00185 Rome, Italy.
Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients.
View Article and Find Full Text PDFJ Neuropsychiatry Clin Neurosci
January 2025
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
Objective: Cognitive impairment is a common nonmotor symptom among individuals with Parkinson's disease (PD). Although cognitive impairment generally develops progressively, individuals with PD-associated mild cognitive impairment (PD-MCI) may revert to being cognitively normal (CN), which is referred to as PD-MCI reversion. Previous studies are inconsistent in whether PD-MCI reverters are at greater risk for PD-MCI recurrence relative to CN individuals.
View Article and Find Full Text PDFPLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
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