Therapeutic approaches for improving cognitive function in the aging brain.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen L
PROVIDER: S-EPMC9773601 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Therapeutic approaches for improving cognitive function in the aging brain.
Chen Lingmin L Jiao Jiao J Zhang Yonggang Y
Frontiers in neuroscience 20221208
The rapid aging of populations around the world has become an unprecedented challenge. Aging is associated with cognitive impairment, including dementia and mild cognitive impairment. Successful drug development for improving or maintaining cognition in the elderly is critically important. Although 4 drugs for improving cognition in Alzheimer's disease have been approved, a variety of potential drugs targeting age-related cognitive impairment are still in development. In addition, non-pharmacolo ...[more]
Similar Datasets
Project description:Down syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability (ID). Although ID can be mild, the average intelligence quotient is in the range of 40-50. All individuals with DS will also develop the neuropathology of Alzheimer's disease (AD) by the age of 30-40 years, and approximately half will display an AD-like dementia by the age of 60 years. DS is caused by an extra copy of the long arm of human chromosome 21 (Hsa21) and the consequent elevated levels of expression, due to dosage, of trisomic genes. Despite a worldwide incidence of one in 700-1,000 live births, there are currently no pharmacological treatments available for ID or AD in DS. However, over the last several years, very promising results have been obtained with a mouse model of DS, the Ts65Dn. A diverse array of drugs has been shown to rescue, or partially rescue, DS-relevant deficits in learning and memory and abnormalities in cellular and electrophysiological features seen in the Ts65Dn. These results suggest that some level of amelioration or prevention of cognitive deficits in people with DS may be possible. Here, we review information from the preclinical evaluations in the Ts65Dn, how drugs were selected, how efficacy was judged, and how outcomes differ, or not, among studies. We also summarize the current state of human clinical trials for ID and AD in DS. Lastly, we describe the genetic limitations of the Ts65Dn as a model of DS, and in the preclinical testing of pharmacotherapeutics, and suggest additional targets to be considered for potential pharmacotherapies.
| S-EPMC4277121 | biostudies-literature
Project description:Cognitive training may promote healthy brain aging and prevent dementia, but results from individual studies are inconsistent. There are disagreements on how to evaluate cognitive training interventions between clinical and basic scientists. Individual labs typically create their own assessment and training materials, leading to difficulties reproducing methods. Here, we advocate for improved interoperability: the exchange and cooperative development of a consensus for cognitive training design, analysis, and result interpretation. We outline five guiding principles for improving interoperability: (i) design interoperability, developing standard design and analysis models; (ii) material interoperability, promoting sharing of materials; (iii) interoperability incentives; (iv) privacy and security norms, ensuring adherence to accepted ethical standards; and (v) interpretability prioritization, encouraging a shared focus on neurobiological mechanisms to improve clinical relevance. Improving interoperability will allow us to develop scientifically optimized, clinically useful cognitive training programs to slow/prevent brain aging.HighlightsInteroperability facilitates progress via resource sharing and comparability.Better interoperability is needed in cognitive training for brain aging research.We adapt an interoperability framework to cognitive training research.We suggest five guiding principles for improved interoperability.We propose an open-source pipeline to facilitate interoperability.
| S-EPMC10441567 | biostudies-literature
Project description:We recently showed that Alzheimer's disease patients have lower plasma concentrations of the phosphatidylcholines (PC16:0/20:5; PC16:0/22:6; and PC18:0/22:6) relative to healthy controls. We now extend these findings by examining associations between plasma concentrations of these PCs with cognition and brain function (measured by regional resting state cerebral blood flow; rCBF) in non-demented older individuals. Within the Baltimore Longitudinal Study of Aging neuroimaging substudy, participants underwent cognitive assessments and brain (15)O-water positron emission tomography. Plasma phosphatidylcholines concentrations (PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6), cognition (California Verbal Learning Test (CVLT), Trail Making Test A&B, the Mini-Mental State Examination, Benton Visual Retention, Card Rotation, and Fluencies-Category and Letter), and rCBF were assessed. Lower plasma phosphatidylcholine concentrations were associated with lower baseline memory performance (CVLT long delay recall task-PC16:0/20:5: -2.17-1.39-0.60 p = 0.001 (β with 95% confidence interval subscripts)) and lower rCBF in several brain regions including those associated with memory performance and higher order cognitive processes. Our findings suggest that lower plasma concentrations of PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6 are associated with poorer memory performance as well as widespread decreases in brain function during aging. Dysregulation of peripheral phosphatidylcholine metabolism may therefore be a common feature of both Alzheimer's disease and age-associated differences in cognition.
| S-EPMC4929698 | biostudies-literature
Project description:ObjectiveTo examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders.MethodsThirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes.ResultsMean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume.ConclusionDistinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population.
| S-EPMC3280054 | biostudies-literature
Project description:BACKGROUND:Across networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sample of patients with psychosis from early to chronic illness stages, this study sought to determine whether the CON and FPN exhibit evidence of accelerated aging in psychotic disorders, confirm associations between network efficiency and cognition, and determine whether reduced network efficiency is observed in early-stage psychosis. METHODS:Resting-state functional magnetic resonance imaging and cognitive data were obtained on 240 patients with psychotic disorder and 178 healthy control participants (HCs). Global efficiency, a measure of functional integration, was calculated for the CON, FPN, subcortical network, and visual network. Associations with age and cognition were assessed and compared between groups. RESULTS:Consistent with accelerated aging, significant group by age interactions reflected significantly stronger relationships between efficiency and age in patients with psychosis than in HCs for both the CON (psychosis: r = -.37; HC: r = -.16) and FPN (psychosis: r = -.31; HC: r = -.05). Accelerated aging was not observed in either the subcortical or visual network, suggesting specificity for cognitive networks that decline earliest in healthy aging. Replicating prior findings, efficiency of both the CON and FPN correlated with cognitive function across all participants (rs > .11, ps < .031). Furthermore, patients with chronic psychosis (p = .004), but not patients with early psychosis (p = .553), exhibited significantly lower FPN efficiency compared with HCs. CONCLUSIONS:Functional integration of higher-order cognitive networks is intact in early psychosis but exhibits evidence of accelerated aging, suggesting the potential for intervention targeting cognition within the early psychosis period.
| S-EPMC6609513 | biostudies-literature
Project description:OBJECTIVE:This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. METHODS:Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. RESULTS:In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF. INTERPRETATION:This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop.
| S-EPMC3241005 | biostudies-literature
Project description:IntroductionNeuroimaging-based 'brain age' can identify individuals with 'advanced' or 'resilient' brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance. We aimed to identify health-related subgroups of older individuals with resilient or advanced brain-PAD, and determine if membership in these subgroups is differentially associated with changes in cognition and frailty over three to five years.MethodsBrain-PAD was predicted from T1-weighted images acquired from 326 community-dwelling older adults (73.8 ± 3.6 years, 42.3% female), recruited from the larger ASPREE (ASPirin in Reducing Events in the Elderly) trial. Participants were grouped as having resilient (n=159) or advanced (n=167) brain-PAD, and latent class analysis (LCA) was performed using a set of cognitive, lifestyle, and health measures. We examined associations of class membership with longitudinal change in cognitive function and frailty deficit accumulation index (FI) using linear mixed models adjusted for age, sex and education.ResultsSubgroups of resilient and advanced brain aging were comparable in all characteristics before LCA. Two typically similar latent classes were identified for both subgroups of brain agers: class 1 were characterized by low prevalence of obesity and better physical health and class 2 by poor cardiometabolic, physical and cognitive health. Among resilient brain agers, class 1 was associated with a decrease in cognition, and class 2 with an increase over 5 years, though was a small effect that was equivalent to a 0.04 standard deviation difference per year. No significant class distinctions were evident with FI. For advanced brain agers, there was no evidence of an association between class membership and changes in cognition or FI.ConclusionThese results demonstrate that the relationship between brain age and cognitive trajectories may be influenced by other health-related factors. In particular, people with age-resilient brains had different trajectories of cognitive change depending on their cognitive and physical health status at baseline. Future predictive models of aging outcomes will likely be aided by considering the mediating or synergistic influence of multiple lifestyle and health indices alongside brain age.
| S-EPMC9846261 | biostudies-literature
Project description:Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.
| S-EPMC6356429 | biostudies-literature
Project description:Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visual manifestations which may be exacerbated by injudicious intervention. Upfront multidisciplinary assessment and coordinated management is crucial from the outset to ensure best short- and long-term functional outcomes. In this review we discuss the clinical and pathological features of the neoplastic entities arising in this location, and their management. We emphasize a clear move towards 'function preserving' diagnostic and therapeutic approaches with novel toxicity-sparing strategies, including targeted therapies.
| S-EPMC10598386 | biostudies-literature
Project description:The concept of brain maintenance refers to the preservation of brain integrity in older age, while cognitive reserve refers to the capacity to maintain cognition in the presence of neurodegeneration or aging-related brain changes. While both mechanisms are thought to contribute to individual differences in cognitive function among older adults, there is currently no "gold standard" for measuring these constructs. Using machine-learning methods, we estimated brain and cognitive age based on deviations from normative aging patterns in the Whitehall II MRI substudy cohort (N = 537, age range = 60.34-82.76), and tested the degree of correspondence between these constructs, as well as their associations with premorbid IQ, education, and lifestyle trajectories. In line with established literature highlighting IQ as a proxy for cognitive reserve, higher premorbid IQ was linked to lower cognitive age independent of brain age. No strong evidence was found for associations between brain or cognitive age and lifestyle trajectories from midlife to late life based on latent class growth analyses. However, post hoc analyses revealed a relationship between cumulative lifestyle measures and brain age independent of cognitive age. In conclusion, we present a novel approach to characterizing brain and cognitive maintenance in aging, which may be useful for future studies seeking to identify factors that contribute to brain preservation and cognitive reserve mechanisms in older age.
| S-EPMC7978127 | biostudies-literature