The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.
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http://dx.doi.org/10.14283/jpad.2017.44 | DOI Listing |
Neurorehabil Neural Repair
January 2025
Department of Physical Medicine and Rehabilitation, Johns Hopkins University, Baltimore, MD, USA.
Background: In humans, most spontaneous recovery from motor impairment after stroke occurs in the first 3 months. Studies in animal models show higher responsiveness to training over a similar time-period. Both phenomena are often attributed to a milieu of heightened plasticity, which may share some mechanistic overlap with plasticity associated with normal motor learning.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Memory Unit, Neurology Department and Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Sant Quintí 77-79, 08041, Barcelona, Spain.
Background: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).
Methods: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution.
Hypertens Res
January 2025
Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
The brainstem plays a vital role in regulating blood pressure, and disruptions to its neural pathways have been linked to hypertension. However, it remains unclear whether subtle microstructural changes in the brainstem are associated with an individual's blood pressure status. This exploratory, cross-sectional study investigated the relationship between brainstem microstructure, myelination, and hypertensive status in 116 cognitively unimpaired adults (aged 22-94 years).
View Article and Find Full Text PDFBrain Commun
January 2025
Department of Clinical Psychology and Psychobiology, Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain.
Previous research has revealed patterns of brain atrophy in subjective cognitive decline, a potential preclinical stage of Alzheimer's disease. However, the involvement of myelin content and microstructural alterations in subjective cognitive decline has not previously been investigated. This study included three groups of participants recruited from the Compostela Aging Study project: 53 cognitively unimpaired adults, 16 individuals with subjective cognitive decline and hippocampal atrophy and 70 with subjective cognitive decline and no hippocampal atrophy.
View Article and Find Full Text PDFJ Neurosci
January 2025
Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697 USA
Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits.
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