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Objective: Brain atrophy measured by structural imaging has been used to quantify resilience against neurodegeneration in Alzheimer's disease. Considering glucose hypometabolism is another marker of neurodegeneration, we quantified metabolic resilience (MR) based on Fluorodeoxyglucose positron emission tomography (FDG PET) and investigated its clinical implications.
Methods: We quantified the MR and other resilience metrics, including brain resilience (BR) and cognitive resilience (CR), using partial least squares path modeling from the ADNI database. A linear mixed-effects model and a Cox proportional hazards model were used to identify the impact of each resilience on longitudinal cognitive function and conversion to dementia, respectively.
Results: A total of 848 participants were included in this study. All resilience metrics (CR, BR, and MR) were associated with slower cognitive decline. Results from the ANOVA test, AIC and BIC values showed that the additional inclusion of MR improved the performances of the linear mixed effect models. In survival analysis, all resilience variables were negatively associated with the risk of conversion to dementia. In line with the results of the linear mixed effects models, the additional inclusion of MR into the models with different resilience variables increased the C-index.
Conclusion: Relative preservation of brain glucose metabolism is a valuable predictor of future cognitive decline and conversion to dementia, adding value to existing resilience metrics. While the utility of FDG PET in clinical settings is limited by cost and accessibility, it might have potential usefulness as a prognostic marker, especially in a context of resilience.
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http://dx.doi.org/10.1016/j.jagp.2024.11.015 | DOI Listing |
Geroscience
September 2025
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Kangwon, 24341, Republic of Korea.
Alzheimer's disease (AD) represents a growing global health burden, underscoring the urgent need for reliable diagnostic and prognostic biomarkers. Although several disease-modifying treatments have recently become available, their effects remain limited, as they primarily delay rather than halt disease progression. Thus, the early and accurate identification of individuals at elevated risk for conversion to AD dementia is crucial to maximize the effectiveness of these therapies and to facilitate timely intervention strategies.
View Article and Find Full Text PDFIntroduction: Plasma glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, has been linked to Alzheimer's disease; however, its prognostic value in cognitively unimpaired (CU) individuals remains unclear.
Methods: We included 949 CU older adults from the A4 preclinical AD trial, and its companion LEARN cohort. Baseline plasma GFAP was measured, and longitudinal associations with cognitive decline, clinical dementia rating (CDR) progression, and imaging biomarkers were assessed over 240 weeks.
Front Neurol
August 2025
Department of Neurology, Hyoja Geriatric Hospital, Kuseong-myeon, Yongin-si, Gyeonggi-do, Republic of Korea.
Background: Mild cognitive impairment (MCI) with amyloid PET positivity represents a prodromal stage of Alzheimer's disease (AD), yet no disease-modifying therapies are currently approved. , traditionally used in East Asian and European ethnomedicine as an oral decoction or standardized extract to support memory and cognitive function, is commonly utilized, however, its efficacy as monotherapy in biomarker-confirmed MCI remains uncertain. Aβ oligomers, produced by abnormal cleavage of amyloid precursor protein, disrupt synaptic function and contribute to cognitive decline.
View Article and Find Full Text PDFMov Disord
September 2025
Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Background: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal manifestation of synucleinopathies and provides a critical window to identify early markers of progression to Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Time-averaged (static) and time-varying (dynamic) functional connectivity between large-scale brain networks may sensitively capture early pathophysiological changes and offer prognostic value beyond structural imaging.
Objectives: To use functional magnetic resonance imaging (fMRI) on a longitudinal iRBD cohort to assess alterations in static and dynamic functional connectivity and explore their relationship with disease conversion and regional neurotransmitter density.
J Parkinsons Dis
September 2025
Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
Individuals with isolated REM sleep behavior disorder (iRBD) are at high risk of developing α-synucleinopathies, particularly Parkinson's disease (PD) and dementia with Lewy bodies (DLB). With the development of potential neuroprotective treatments for synucleinopathies, including PD, identifying clinical features that can allow for tracking subtle changes in prodromal disease and thereby monitoring risk of phenoconversion in iRBD is paramount. Subtle motor deficits have been suggested to be present in iRBD, making them potentially important clinical markers for predicting future phenoconversion.
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