Down syndrome (DS) is now viewed as a genetic type of Alzheimer's disease (AD), given the near-universal presence of AD pathology in middle adulthood and the elevated risk for developing clinical AD in DS. As the field of DS prepares for AD clinical intervention trials, there is a strong need to identify cognitive measures that are specific and sensitive to the transition from being cognitively stable to the prodromal (e.g., Mild Cognitive Impairment-Down syndrome) and clinical AD (e.g., Dementia) stages of the disease in DS. It is also important to determine cognitive measures that map onto biomarkers of early AD pathology during the transition from the preclinical to the prodromal stage of the disease, as this transition period is likely to be targeted and tracked in AD clinical trials. The present chapter discusses the current state of research on cognitive measures that could be used to screen/select study participants and as potential outcome measures in future AD clinical trials with adults with DS. In this chapter, we also identify key challenges that need to be overcome and questions that need to be addressed by the DS field as it prepares for AD clinical trials in the coming years.
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http://dx.doi.org/10.1016/bs.irrdd.2022.05.006 | DOI Listing |
J Neural Transm (Vienna)
January 2025
Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China.
In major depressive disorder (MDD), alterations in ghrelin levels and cognitive impairment coexist, yet their association has remained largely elusive. This study aimed to investigate the association between ghrelin levels and cognition in both MDD patients and healthy controls (HCs) while also exploring sex-specific differences in this correlation. A total of 155 Chinese Han subjects, including 90 first-episode drug-naive MDD patients and 65 HCs, were enrolled.
View Article and Find Full Text PDFJ Neurol
January 2025
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Villaroel 170, 08036, Barcelona, Spain.
Plasma tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217) have demonstrated high accuracy for Alzheimer's disease (AD) diagnosis, defined by CSF/PET amyloid beta (Aβ) positivity, but most studies have been performed in research cohorts, limiting their generalizability. We studied plasma p-tau217 and p-tau181 for CSF Aβ status discrimination in a cohort of consecutive patients attending an academic memory clinic in Spain (July 2019-June 2024). All patients had CSF AD biomarkers performed as part of their routine clinical assessment.
View Article and Find Full Text PDFJ Neurol
January 2025
Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays.
View Article and Find Full Text PDFJ Psychiatry Neurosci
January 2025
From the Faculty of Medicine, University of Ottawa, Ottawa, Ont. (Djimbouon); the Mind, Brain Imaging and Neuroethics Unit, Institute of Mental Health Research, Royal Ottawa Mental Health Centre, University of Ottawa, Ottawa, Ont. (Djimbouon, Northoff); the Faculty of Mathematics and Natural Sciences, Institute of Experimental Psychology, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany (Klar); and the Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany (Klar).
Background: Schizophrenia is hypothesized to involve a disturbance in the temporal dynamics of self-processing, specifically within the interoceptive, exteroceptive, and cognitive layers of the self. This study aimed to investigate the intrinsic neural timescales (INTs) within these self-processing layers among people with schizophrenia.
Methods: We conducted a functional magnetic resonance imaging (fMRI) study to investigate INTs, as measured by the autocorrelation window, among people with schizophrenia and healthy controls during both resting-state and task (memory encoding and retrieval) conditions.
Biol Psychiatry
January 2025
Translational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh; Department of Neuroscience, Dietrich School of Arts and Sciences, University of Pittsburgh; Center for the Neural Basis of Cognition, Carnegie Mellon University. Electronic address:
Background: Certain cognitive processes require inhibition provided by the somatostatin (SST) class of gamma-aminobutyric acid (GABA) neurons in the dorsolateral prefrontal cortex (DLPFC). This inhibition onto pyramidal neuron dendrites depends on both SST and GABA signaling. Although SST mRNA levels are lower in the DLPFC in schizophrenia, it is not known if SST neurons exhibit alterations in the capacity to synthesize GABA, principally via the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67).
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