Aging brain最新文献

We investigated age-related trends in the topology and hierarchical organization of brain structural and functional networks using diffusion-weighted imaging and resting-state fMRI data from a large cohort of healthy aging adults. At the cross-modal level, we explored age-related patterns in the RC involvement of different functional subsystems using a high-resolution functional parcellation. We further assessed age-related differences in the structure–function coupling as well as the network vulnerability to damage to rich club connectivity.

Regardless of age, the structural and functional brain networks exhibited a rich club organization and small-world topology. In older individuals, we observed reduced integration and segregation within the frontal-occipital regions and the cerebellum along the brain's medial axis. Additionally, functional brain networks displayed decreased integration and increased segregation in the prefrontal, centrotemporal, and occipital regions, and the cerebellum. In older subjects, structural networks also exhibited decreased within-network and increased between-network RC connectivity. Furthermore, both within-network and between-network RC connectivity decreased in functional networks with age. An age-related decline in structure–function coupling was observed within sensory-motor, cognitive, and subcortical networks. The structural network exhibited greater vulnerability to damage to RC connectivity within the language-auditory, visual, and subcortical networks. Similarly, for functional networks, increased vulnerability was observed with damage to RC connectivity in the cerebellum, language-auditory, and sensory-motor networks. Overall, the network vulnerability decreased significantly in subjects older than 70 in both networks. Our findings underscore significant age-related differences in both brain functional and structural RC connectivity, with distinct patterns observed across the adult lifespan.

The aging process induces neurochemical alterations in different brain regions, including hypothalamus. This pivotal area of the central nervous system (CNS) is crucial for detection and integration of nutritional and hormonal signals from the periphery of the body to maintain metabolic homeostasis. Astrocytes support the CNS homeostasis, energy metabolism, and inflammatory response, as well as increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions and in gliocrine system. In this study, we aimed to investigate the age-dependent mRNA expression of adenosine receptors, the insulin-like growth factor 1 receptor (IGF1R), and the hypoxia-inducible factor 1α (HIF1α), in addition to the levels of IGF1 and HIF1α in hypothalamic astrocyte cultures derived from newborn, adult, and aged rats. Our results revealed age-dependent changes in adenosine receptors, as well as a decrease in IGF1R/IGF1 and HIF1α. Of note, adenosine receptors, IGF1, and HIF1α are affected by inflammatory, redox, and metabolic processes, which can remodel hypothalamic properties, as observed in aging brain, reinforcing the role of hypothalamic astrocytes as targets for understanding the onset and/or progression of age-related diseases.

According to the maintenance hypothesis (Nyberg et al., 2012), structural integrity of the brain’s grey matter helps to preserve cognitive functioning into old age. A corollary of this hypothesis that can be tested in cross-sectional data is that grey-matter structural integrity and general cognitive ability are positively associated in old age. Building on Köhncke et al. (2021), who found that region-specific latent factors of grey-matter integrity are positively associated with episodic memory ability among older adults, we examine associations between general factors of grey-matter integrity and a general factor of cognitive ability in a cross-sectional sample of 1466 participants aged 60–88 years, 319 of whom contributed imaging data. Indicator variables based on T1-weighted images (voxel-based morphometry, VBM), magnetization-transfer imaging (MT), and diffusion tensor imaging-derived mean diffusivity (MD) had sufficient portions of variance in common to establish latent factors of grey-matter structure for a comprehensive set of regions of interest (ROI). Individual differences in grey-matter factors were positively correlated across neocortical and limbic areas, allowing for the definition of second-order, general factors for neocortical and limbic ROI, respectively. Both general grey-matter factors were positively correlated with general cognitive ability. For the basal ganglia, the three modality-specific indicators showed heterogenous loading patterns, and no reliable associations of the general grey-matter factor to general cognitive ability were found. To provide more direct tests of the maintenance hypothesis, we recommend applying the present structural modeling approach to longitudinal data, thereby enhancing the physiological validity of latent constructs of brain structure.

Cognitive decline as part of mental ageing is typically assessed with standardized tests; below-average performance in such tests is used as an indicator for pathological cognitive aging. In addition, morphological and functional changes in the brain are used as parameters for age-related pathological decline in cognitive abilities. However, there is no simple link between the trajectories of changes in cognition and morphological or functional changes in the brain. Furthermore, below-average test performance does not necessarily mean a significant impairment in everyday activities. It therefore appears crucial to record individual everyday tasks and their cognitive (and other) requirements in functional terms. This would also allow reliable assessment of the ecological validity of existing and insufficient cognitive skills. Understanding and dealing with the phenomena and consequences of mental aging does of course not only depend on cognition. Motivation and emotions as well personal meaning of life and life satisfaction play an equally important role. This means, however, that cognition represents only one, albeit important, aspect of mental aging. Furthermore, creating and development of proper assessment tools for functional cognition is important. In this contribution we would like to discuss some aspects that we consider relevant for a holistic view of the aging mind and promote a strengthening of a multidisciplinary approach with close cooperation between all basic and applied sciences involved in aging research, a quick translation of the research results into practice, and a close cooperation between all disciplines and professions who advise and support older people.

Hippocampal sclerosis of aging (HS-A) is a common degenerative neuropathology in older individuals and is associated with dementia. HS-A is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy in individuals with HS-A. To better understand the onset and progression of hippocampal atrophy in HS-A, we examined longitudinal hippocampal atrophy using serial MRI in participants with HS-A at autopsy (HS-A+, n = 8) compared to participants with limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) without HS-A (n = 13), Alzheimer’s disease neuropathologic change (ADNC) without HS-A or LATE-NC (n = 16), and those without these pathologies (n = 7). We found that participants with HS-A had lower hippocampal volumes compared to the other groups, and this atrophy preceded the onset of dementia. There was also some evidence that rates of hippocampal volume loss were slightly slower in those with HS-A. Together, these results suggest that the disproportionate hippocampal atrophy seen in HS-A may begin early prior to dementia.

Blood pressure variability (BPV), independent of mean blood pressure levels, is associated with cerebrovascular disease burden on MRI and postmortem evaluation. However, less is known about relationships with markers of cerebrovascular dysfunction, such as diminished spontaneous brain activity as measured by the amplitude of low frequency fluctuations (ALFF), especially in brain regions with vascular and neuronal vulnerability in aging. We investigated the relationship between short-term BPV and concurrent regional ALFF from resting state fMRI in a sample of community-dwelling older adults (n = 44) and healthy younger adults (n = 49). In older adults, elevated systolic BPV was associated with lower ALFF in widespread medial temporal regions and the anterior cingulate cortex. Higher systolic BPV in younger adults was also related to lower ALFF in the medial temporal lobe, albeit in fewer subregions, and the amygdala. There were no significant associations between systolic BPV and ALFF across the right/left whole brain or in the insular cortex in either group. Findings suggest a possible regional vulnerability to cerebrovascular dysfunction and short-term fluctuations in blood pressure. BPV may be an understudied risk factor for cerebrovascular changes in aging.