Neurobiology of Aging最新文献

Brazilian green propolis (propolis) is a chemically complex resinous substance that is a potentially viable therapeutic agent for Alzheimer’s disease. Herein, propolis induced a transient increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in Neuro-2A cells; moreover, propolis-induced [Ca²⁺]_i elevations were suppressed prior to 24-h pretreatment with amyloid-β. To reveal the effect of [Ca²⁺]_i elevation on impaired cognition, we performed memory-related behavioral tasks in APP-KI mice relative to WT mice at 4 and 12 months of age. Propolis, at 300–1000 mg/kg/d for 8 wk, significantly ameliorated cognitive deficits in APP-KI mice at 4 months, but not at 12 months of age. Consistent with behavioral observations, injured hippocampal long-term potentiation was markedly ameliorated in APP-KI mice at 4 months of age following repeated propolis administration. In addition, repeated administration of propolis significantly activated intracellular calcium signaling pathway in the CA1 region of APP-KI mice. These results suggest a preventive effect of propolis on cognitive decline through the activation of intracellular calcium signaling pathways in CA1 region of AD mice model.

Through the application of machine learning algorithms to neuroimaging data the brain age methodology was shown to provide a useful individual-level biological age prediction and identify key brain regions responsible for the prediction. In this study, we present the methodology of constructing a rhesus macaque brain age model using a machine learning algorithm and discuss the key predictive brain regions in comparison to the human brain, to shed light on cross-species primate similarities and differences. Structural information of the brain (e.g., parcellated volumes) from brain magnetic resonance imaging of 43 rhesus macaques were used to develop brain atlas-based features to build a brain age model that predicts biological age. The best-performing model used 22 selected features and achieved an R² of 0.72. We also identified interpretable predictive brain features including Right Fronto-orbital Cortex, Right Frontal Pole, Right Inferior Lateral Parietal Cortex, and Bilateral Posterior Central Operculum. Our findings provide converging evidence of the parallel and comparable brain regions responsible for both non-human primates and human biological age prediction.

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (β=0.048, p_FDR=0.016) and household (β=0.075, p_FDR<0.001) physical activity. Global fractional anisotropy (β=0.042, p_FDR=0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (β=-0.026, p_FDR=0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (p_all>0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship.

Psychosis in Alzheimer’s Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

This study aimed to determine associations between modifiable dementia risk factors (MDRF), across domains mood symptomatology, lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology, with cognition, beta-amyloid (Aβ) and tau, and brain volume. Middle-aged/older adults (n=82) enrolled in a sub-study of the Healthy Brain Project completed self-report questionnaires and a neuropsychological battery. Cerebrospinal fluid levels of Aβ 1–42, total tau (t-tau), and phosphorylated tau (p-tau₁₈₁) (Roche Elecsys), and MRI markers of hippocampal volume and total brain volume were obtained. Participants were classified as no/single domain risk (≤1 domains) or multidomain risk (≥2 domains). Compared to the no/single domain risk group, the multidomain risk group performed worse on the Preclinical Alzheimer’s Cognitive Composite (d=0.63, p=.005), and Executive Function (d=0.50, p=.016), and had increased p-tau₁₈₁ (d=0.47, p=.042) and t-tau (d=0.54, p=.021). In middle-aged/older adults, multidomain MDRFs were related to increases in tau and worse cognition, but not Aβ or brain volume. Findings suggest that increases in AD biomarkers are apparent in midlife, particularly for individuals with greater burden, or variety of MDRFs.

Aging affects the scalp-to-cortex distance (SCD) and the comprising tissues. This is crucial for noninvasive neuroimaging and brain stimulation modalities as they rely on traversing from the scalp to the cortex or vice versa. The specific relationship between aging and these tissues has not been comprehensively investigated. We conducted a study on 250 younger and older adults to examine age-related differences in SCD and its constituent tissues. We identified region-specific differences in tissue thicknesses related to age and sex. Older adults exhibit larger SCD in the frontocentral regions compared to younger adults. Men exhibit greater SCD in the inferior scalp regions, while women show similar-to-greater SCD values in regions closer to the vertex compared to men. Younger adults and men have thicker soft tissue layers, whereas women and older adults exhibit thicker compact bone layers. CSF is considerably thicker in older adults, particularly in men. These findings emphasize the need to consider age, sex, and regional differences when interpreting SCD and its implications for noninvasive neuroimaging and brain stimulation.

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer’s disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer’s disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks.

Astrocytes play an important role in neuroinflammation by producing proinflammatory molecules. In response to various stressful stimuli, astrocytes can become senescent or reactive, both are present in age-associated cognitive impairment and other neurodegenerative diseases, and contribute to neuroinflammation. However, there are no studies that compare the cytokines secreted by these types of astrocytes in the brain during aging. Hence, we aimed to broaden the picture of the secretory profiles and to differentiate the variability between them. Therefore, a systematic review was conducted following the guidelines of the “Reporting Items for Systematic Review and Meta-Analyses”. Only three studies that met the inclusion terms evaluated age-related cytokine secretion, however, no evaluation of senescence or gliosis was performed. Consequently, to increase the spectrum of the review, studies where those phenotypes were induced and cytokines determined were included. Although some cytokines were common for gliosis and senescence, some interesting differences were also found. The dissimilarities in cytokines secretion between these phenotypes could be studied in the future as potential markers.