Alzheimer's disease (AD) is an aging-related, degenerative brain disease of adults. Most (∼95%) of AD occurs sporadically and is associated with early-appearing deficits in brain regional glucose uptake, changes in cerebrospinal fluid (CSF) AD-related proteins, regional brain atrophy, and oxidative stress damage. We treated mild-moderate AD individuals with R(+)-pramipexole-dihydrochloride (R(+)PPX), a neuroprotective, lipophilic-cation, free-radical scavenger that accumulates into brain and mitochondria. 19 subjects took R(+)PPX twice a day in increasing daily doses up to 300 mg/day under a physician-sponsor IND (60,948, JPB), IRB-approved protocol and quarterly external safety committee monitoring. 15 persons finished and contributed baseline and post-treatment serum, lumbar spinal fluid, brain 18F-2DG PET scans, and ADAS-Cog scores. ADAS-Cog scores did not change (n = 1), improved (n = 2), declined 1-3 points (n = 5), or declined 4-13 points (n = 8) over 6 months of R(+)PPX treatment. Serum PPX levels were not related to changes in ADAS-Cog scores. Fasting AM serum PPX levels at 6 months varied considerably across subjects and correlated strongly with CSF [PPX] (r = 0.97, p < 0.0001). CSF [PPX] was not related to CSF [Aβ(42)], [Tau], or [P-Tau]. Regional 18F-2DG measures of brain glucose uptake demonstrated a 3-6% decline during R(+)PPX treatment. 56 mild-moderate adverse events occurred, 26 probably/definitely related to R(+)PPX use, with 4 withdrawals. R(+)PPX was generally well-tolerated and entered brain extracellular space linearly. Further studies of R(+)PPX in AD should include a detailed pharmacokinetic study of peak and trough serum [PPX] variations among subjects prior to planning any larger studies that would be needed to determine efficacy in altering disease progression.
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http://dx.doi.org/10.3233/JAD-150788 | DOI Listing |
Neuropsychopharmacol Rep
March 2025
Thalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Contradictory results for the association between metformin intake and changes in cognitive function have been reported. We attempted to overview systematic reviews and meta-analyses showing the role of metformin, as mono or combination therapy, in cognitive performance alterations among patients with type 2 diabetes mellitus (T2DM) and to determine the quality of the evidence as well. To find the English-written reviews, a literature search was conducted on PubMed, Web of Science, Scopus, Cochrane Library, Trip, and Google Scholar by May 1, 2023.
View Article and Find Full Text PDFObjectives: Numerous studies have examined the effects of physical activity on cognitive performance and executive function in people with Alzheimer's disease (AD), although the findings are not entirely consistent. There are also insufficient study reviews for specific workout and assessment tool types. Therefore, the purpose of this study was to systematically investigate the effects of aerobic exercise on the quality of life, cognitive performance and depressive symptoms in people with AD.
View Article and Find Full Text PDFJ Integr Neurosci
December 2024
Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
Background: The relationship between subregion atrophy in the entire temporal lobe and subcortical nuclei and cognitive decline at various stages of Alzheimer's disease (AD) is unclear.
Methods: We selected 711 participants from the AD Neuroimaging Initiative (ADNI) database, which included 195 cases of cognitively normal (CN), 271 cases of early Mild cognitive impairment (MCI) (EMCI), 132 cases of late MCI (LMCI), and 113 cases of AD. we looked at how subregion atrophy in the temporal lobe and subcortical nuclei correlated with cognition at different stages of AD.
Complement Ther Med
December 2024
School of Acu-Mox and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Sichuan Provincial Acupuncture Clinical Medicine Research Center, Chengdu, China. Electronic address:
Objectives: Acupuncture is a promising therapy for amnestic mild cognitive impairment (aMCI). Growing evidence suggest that alterations in the microbiota-gut-brain (MGB) axis contribute to the development and progression of aMCI. However, little is known about whether and how acupuncture change the MGB axis of aMCI individuals.
View Article and Find Full Text PDFCurr Alzheimer Res
January 2025
Department of Neurology, Shanghai Yangpu District Kongjiang Hospital, Shanghai, China.
Background: Alzheimer's Disease (AD) is characterized by a progressive neurodegenerative process leading to cognitive decline and functional impairment. Endocrine factors, particularly sex hormones and their binding proteins, play a critical role in AD pathophysiology. Understanding the relationship between these factors and AD is essential for developing targeted interventions.
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