Background: Acetylcholinesterase inhibitors are considered standard of care for Alzheimer's disease in many countries. Galantamine is an acetylcholinesterase inhibitor that may also act via allosteric modulation of nicotinic acetylcholine receptors. Therefore, it may provide benefits compared with other acetylcholinesterase inhibitors. The present study compared galantamine (n = 116) with donepezil (n = 117) in a double-blind trial at nine hospitals in China.
Methods: After washout of any previous acetylcholinesterase inhibitors, subjects with mild to moderate Alzheimer's disease received galantamine or donepezil for 16 weeks.
Results: Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog/11) scores improved significantly from baseline in both treatment arms, with a significant difference in favor of galantamine on the "language" functional area (P = 0.035). Significantly more galantamine-treated patients responded to treatment (defined as a reduction in ADAS-cog/11 score of >4, >7, or >10 points; all P < 0.05), and had an ADAS-cog/11 score < 20 at end point (P = 0.015). Both treatments were well tolerated, although fewer galantamine-treated patients experienced gastrointestinal adverse events compared with donepezil (30% versus 48%).
Conclusion: Cognitive function improved significantly in subjects with mild to moderate Alzheimer's disease treated with galantamine or donepezil, and both treatments were generally well tolerated. Significant benefits for galantamine over donepezil were observed for language and response to treatment.
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http://dx.doi.org/10.2147/NDT.S38747 | DOI Listing |
Adv Sci (Weinh)
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.
View Article and Find Full Text PDFActa Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFNeurotherapeutics
January 2025
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. Electronic address:
Amyloidogenic protein aggregation is a pathological hallmark of Alzheimer's Disease (AD). As such, this critical feature of the disease has been instrumental in guiding research on the mechanistic basis of disease, diagnostic biomarkers and preventative and therapeutic treatments. Here we review identified molecular triggers and modulators of aggregation for two of the proteins associated with AD: amyloid beta and tau.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
First Operating Room, The First Hospital of Jilin University, Changchun, China. Electronic address:
Background: Certain peripheral proteins are believed to be involved in the development of Alzheimer's disease (AD), but the roles of other new protein biomarkers are still unclear. Current treatments aim to manage symptoms, but they are not effective in stopping the progression of the disease. New drug targets are needed to prevent Alzheimer's disease.
View Article and Find Full Text PDFNeuroscience
January 2025
Departamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, MEC, Av. Italia 3318, Montevideo, CP 11600, Uruguay; Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Iguá, Montevideo, 4225, CP 11400, Uruguay. Electronic address:
Local protein synthesis (LPS) in axons is now recognized as a physiological process, participating both in the maintenance of axonal function and diverse plastic phenomena. In the last decades of the 20th century, the existence and function of axonal LPS were topics of significant debate. Very early, axonal LPS was thought not to occur at all and was later accepted to play roles only during development or in response to specific conditions.
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