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A recent study showed significant sex-modulated aging effects on plasma total tau protein in individuals with subjective memory complaints ( 17). Sex was also found to modulate aging effects on brain atrophy in healthy adults ( 16). ![]() Furthermore, emerging evidence suggests that women differ from men in multiple neurological aspects, including brain function ( 12), cognitive domains, cognitive decline ( 13, 14), and effects of amyloid deposition ( 15). Investigating age-related effects on neuronal activity among amyloid positive and amyloid negative MCI patients is potentially critical for developing therapeutic strategies to slow or prevent more severe disease progression. Amyloid positive MCI is the prodromal stage that have a higher incidence of AD conversion. Identifying pathological aging effects in subjects with neurodegenerative disease may provide critical insights into underlying disease mechanisms. Neurodegenerative conditions can alter the brain trajectory that differs from normal aging. ![]() Neurodegenerative conditions could lead to the alteration in caudate nucleus, which were mainly reported in Parkinson's disease ( 10, 11), however, the role of caudate in mild cognitive impairment (MCI) or Alzheimer's dementia (AD) largely remains unknown. In addition, damage to the caudate nucleus is accompanied by decline in inhibitory processes, executive control, and cognitive speed similar to the effects observed in normal aging ( 9). Structural magnetic resonance imaging (MRI) studies in elderly adults demonstrated the multifaceted role of caudate nucleus with evidence that caudate atrophy is related to various behavioral performances, including slower walking speed ( 7) and longer action selection time ( 8). Task functional magnetic resonance imaging (fMRI) data showed that, in a virtual navigation task, older adults had significant activity in the caudate nucleus while young adults had significant activity in the hippocampus, suggesting that the aging process involves a shift of functional demands from hippocampus toward the caudate nucleus during navigation ( 6). Cortical-caudate functional connectivity was revealed to be less differentiated in older adults compared to younger adults, and age-related differences in caudate function were associated with memory decline in normal aging ( 5). Caudate nucleus is of particular interest in the frontostriatal system because caudate function and structure is sensitive to age-related differences between healthy young and old adults. While episodic memories are established and maintained by an interplay between the medial temporal lobe and other cortical regions, the aging-related degradation of the frontostriatal system is suggested to be a driving factor of episodic memory decline in older adults ( 4). The medial temporal lobe memory system and frontostriatal system are well-recognized as two fundamental neural systems supporting episodic memory and executive function ( 2, 3). These issues may be especially important for studies of mild cognitive impairment (MCI), known to be a heterogeneous condition ( 1). An independent cohort was used to validate the sex-dependent aging effects in MCI.īrain aging is characterized by considerable heterogeneity, including the differences between regions and the variability induced by demographic factors and symptomatic or presymptomatic pathology, such as the presence of brain amyloid. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. ![]() LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. ![]() Two hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Then you can follow the links in the definition page to get more word definitions. As you type, Dictionary homes in on the word you are looking for. The home page contains a randomly selected word cloud which will pique your curiosity and help you improve your vocabulary, while the search box allows you to find specific words easily. The dictionary definitions are stored locally, and because it's ad-free there's no need for a network connection. 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