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Introduction: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aβ), remains unclear.
Methods: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aβ. We next examined associations between cytokine levels and neuroimaging biomarkers of Aβ/tau/neurodegeneration.
Results: Higher IL-12p70 was associated with slower cognitive decline in the setting of higher Aβ (false discovery rate [FDR] = 0.0023), whereas higher IFN-γ was associated with slower cognitive decline independent of Aβ (FDR = 0.013). Higher IL-12p70 was associated with less tau and neurodegeneration in participants with higher Aβ.
Discussion: Immune dysregulation is implicated in early-stage cognitive decline, and greater IL-12/IFN-γ axis activation may be protective against cognitive decline and early-stage AD progression.
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http://dx.doi.org/10.1002/alz.12399 | DOI Listing |
Neurology
October 2025
Department of Radiology, Mayo Clinic, Rochester, MN.
Background And Objectives: The relationship between insomnia and cognitive decline is poorly understood. We investigated associations between chronic insomnia, longitudinal cognitive outcomes, and brain health in older adults.
Methods: From the population-based Mayo Clinic Study of Aging, we identified cognitively unimpaired older adults with or without a diagnosis of chronic insomnia who underwent annual neuropsychological assessments (z-scored global cognitive scores and cognitive status) and had quantified serial imaging outcomes (amyloid-PET burden [centiloid] and white matter hyperintensities from MRI [WMH, % of intracranial volume]).
Gerontologist
September 2025
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612United States.
Background And Objectives: Cognition may be influenced by health-related factors such as blood pressure (BP). However, variations in BP may differentially affect cognition across race. This study investigates BP and cognitive decline in older Black and White adults.
View Article and Find Full Text PDFJ Gerontol B Psychol Sci Soc Sci
September 2025
Institute of Gerontology, Wayne State University, Detroit, Michigan, United States.
Objectives: In this study, we examined the extent to which older adult social activity participation and perceptions of neighborhoods correspond with risks of cognitive impairment and no dementia (CIND) and dementia.
Methods: We predicted the risk of both CIND and dementia in a series of Cox proportional hazards analyses among older adults across a ten-year period. Utilizing data from the Health and Retirement Study (HRS, N = 15,020), we examined whether social activity participation corresponded with reduced risk of CIND and dementia, as well as whether perceptions of neighborhood conditions, social cohesion, and neighborhood disorder moderated the effects of social activity participation.
Brain
September 2025
Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016 Granada, Spain.
Primary coenzyme Q (CoQ) deficiency is a mitochondrial disorder with variable clinical presentation and limited response to standard CoQ10 supplementation. Recent studies suggest that 4-hydroxybenzoic acid (4-HBA), a biosynthetic precursor of CoQ, may serve as a substrate enhancement treatment in cases caused by pathogenic variants in COQ2, a gene encoding a key enzyme in CoQ biosynthesis. However, it remains unclear whether 4-HBA is required throughout life to maintain health, whether it offers advantages over CoQ10 treatment, and whether these findings are translatable to humans.
View Article and Find Full Text PDFAnn Acad Med Singap
August 2025
Dementia Research Centre (Singapore), Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore.
Introduction: Interpretation and analysis of magnetic resonance imaging (MRI) scans in clinical settings comprise time-consuming visual ratings and complex neuroimage processing that require trained professionals. To combat these challenges, artificial intelligence (AI) techniques can aid clinicians in interpreting brain MRI for accurate diagnosis of neurodegenerative diseases but they require extensive validation. Thus, the aim of this study was to validate the use of AI-based AQUA (Neurophet Inc.
View Article and Find Full Text PDF