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Drug Development.
Alzheimers Dement
December 2024
Centre for Addiction and Mental Health, Toronto, ON, Canada.
Background: Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5-containing GABAA receptors (α5-GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5-positive allosteric modulator (α5-PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
EQT Life Sciences Partners, Amsterdam, 1071 DV Amsterdam, Netherlands.
Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.
Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.
Background: Abnormal glucose metabolism in AD brains correlates with cognitive deficits. The glucose changes are consistent with brain thiamine (vitamin B1) deficiency. In animals, thiamine deficiency causes multiple AD-like changes including memory loss, neuron loss, brain inflammation, enhanced phosphorylation of tau, exaggerated plaque formation and elevated advanced glycation end products (AGE).
View Article and Find Full Text PDFBackground: Clinical outcome assessments (COAs) that measure functional capacities are key tools to evaluate efficacy in Alzheimer's disease (AD) clinical trials. The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale is frequently used to assess changes in both basic and instrumental activities of daily living, but there is no clear consensus on what magnitude of change on this scale may be considered clinically meaningful. To address this question, we conducted anchor-based analyses (as recommended by the FDA) to explore meaningful within-patient/participant change thresholds on the ADCS-ADL.
View Article and Find Full Text PDFIt is well recognised that Alzheimer's disease and related dementia disorders (ADRD) are associated with very high societal costs. The total global costs of dementia have been estimated to over 1.3 trillion US$ annually (Wimo, Seeher et al.
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