scholarly journals Heritability of Brain Resilience to Perturbation in Humans

NeuroImage ◽  
2021 ◽  
pp. 118013
Author(s):  
Arianna Menardi ◽  
Andrew E. Reineberg ◽  
Antonino Vallesi ◽  
Naomi P. Friedman ◽  
Marie T. Banich ◽  
...  
Keyword(s):  
2021 ◽  
Vol 22 (1) ◽  
pp. 461
Author(s):  
Sónia C. Correia ◽  
Nuno J. Machado ◽  
Marco G. Alves ◽  
Pedro F. Oliveira ◽  
Paula I. Moreira

The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 918-918
Author(s):  
Blake Neyland ◽  
Christina Hugenschmidt ◽  
Samuel Lockhart ◽  
Laura Baker ◽  
Suzanne Craft ◽  
...  

Abstract Brain pathologies are increasingly understood to confer mobility risk, but the malleability of functional brain networks may be a mechanism for mobility reserve. In particular, white matter hyperintensities (WMH) are strongly associated with mobility and alter functional network connectivity. To assess the potential role of brain networks as a mechanism of mobility reserve, 116 participants with MRI from the Brain Networks and Mobility Function (B-NET) were categorized into 4 groups based on median splits of SPPB scores and WMH burden: Expected Healthy (EH: low WMH, SPPB>10, N=45), Expected Impaired (EI: high WMH, SPPB10, N=24), Unexpected Impaired (EI: low WMH, SPPB<10, N=10) and Unexpected Unhealthy (UH: low WMH, SPPB<10, N=37). Functional brain networks were calculated using graph theory methods and white matter hyperintensities were quantified with the Lesion Segmentation Toolbox (LST) in SPM12. Somatomotor cortex community structure (SMC-CS) was similar between UH and EH with both having higher consistency than EI and UI. However, UH displayed a unique increase in second-order connections between the motor cortex and the anterior cingulate. It is possible that this increase in connections is a signal of higher reserve or resilience in UH participants and may indicate a mechanism of compensation in regards to mobility function and advanced WMH burden. These data suggest functional brain networks may be a mechanism for mobility resilience in older adults at mobility risk due to WMH burden.


2021 ◽  
pp. 1-12
Author(s):  
Di Hu ◽  
Chuning Liu ◽  
Kai Xia ◽  
Amy Abramowitz ◽  
Guorong Wu ◽  
...  

Background: With the rapid development of neurobiology and neuroimaging technologies, mounting evidence shows that Alzheimer’s disease (AD) is caused by the build-up of two abnormal proteins, amyloid-β plaques (A) and neurofibrillary tangles (T). Over time, these AD-related neuropathological burdens begin to spread throughout the brain, which results in the characteristic progression of symptoms in AD. Objective: Although tremendous efforts have been made to link biological indicators to the progression of AD, limited attention has been paid to investigate the multi-factorial role of socioeconomic status (SES) in the prevalence or incidence of AD. There is high demand to explore the synergetic effect of sex and SES factors in moderating the neurodegeneration process caused by the accumulation of A and T biomarkers. Methods: We carry out a meta-data analysis on the longitudinal neuroimaging data, clinical outcomes, genotypes, and demographic data in Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). Results: Our major findings include 1) education and occupation show resilience effects at the angular gyrus, superior parietal lobule, lateral occipital-temporal sulcus, and posterior transverse collateral sulcus where we found significant slowdown of neurodegeneration due to higher education level or more advanced occupation rank; 2) A and T biomarkers manifest different spatial patterns of brain resilience; 3) BDNF (brain-derived neurotrophic factor) single nucleotide polymorphism (SNP) rs10835211 shows strong association to the identified resilience effect; 4) the identified resilience effect is associated with the clinical manifestation in memory, learning, and organization performance. Conclusion: Several brain regions manifest resilience from SES to A and T biomarkers. BDNF SNPs have a potential association with the resilience effect from SES. In addition, cognitive measures of learning and memory demonstrate the resilience effect.


Cortex ◽  
2015 ◽  
Vol 64 ◽  
pp. 293-309 ◽  
Author(s):  
Emiliano Santarnecchi ◽  
Simone Rossi ◽  
Alessandro Rossi

2018 ◽  
Vol 65 (4) ◽  
pp. e12515 ◽  
Author(s):  
Rubén Corpas ◽  
Christian Griñán-Ferré ◽  
Verónica Palomera-Ávalos ◽  
David Porquet ◽  
Pablo García de Frutos ◽  
...  
Keyword(s):  

Stroke ◽  
2021 ◽  
Author(s):  
Natalia S. Rost ◽  
James F. Meschia ◽  
Rebecca Gottesman ◽  
Lisa Wruck ◽  
Karl Helmer ◽  
...  

Stroke is a leading cause of the adult disability epidemic in the United States, with a major contribution from poststroke cognitive impairment and dementia (PSCID), the rates of which are disproportionally high among the health disparity populations. Despite the PSCID’s overwhelming impact on public health, a knowledge gap exists with regard to the complex interaction between the acute stroke event and highly prevalent preexisting brain pathology related to cerebrovascular and Alzheimer disease or related dementia. Understanding the factors that modulate PSCID risk in relation to index stroke event is critically important for developing personalized prognostication of PSCID, targeted interventions to prevent it, and for informing future clinical trial design. The DISCOVERY study (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery), a collaborative network of thirty clinical performance clinical sites with access to acute stroke populations and the expertise and capacity for systematic assessment of PSCID will address this critical challenge. DISCOVERY is a prospective, multicenter, observational, nested-cohort study of 8000 nondemented ischemic and hemorrhagic stroke patients enrolled at the time of index stroke and followed for a minimum of 2 years, with serial cognitive evaluations and assessments of functional outcome, with subsets undergoing research magnetic resonance imaging and positron emission tomography and comprehensive genetic/genomic and fluid biomarker testing. The overall scientific objective of this study is to elucidate mechanisms of brain resilience and susceptibility to PSCID in diverse US populations based on complex interplay between life-course exposure to multiple vascular risk factors, preexisting burden of microvascular and neurodegenerative pathology, the effect of strategic acute stroke lesions, and the mediating effect of genomic and epigenomic variation.


2018 ◽  
Vol 56 (2) ◽  
pp. 1502-1516 ◽  
Author(s):  
Rubén Corpas ◽  
Christian Griñán-Ferré ◽  
Eduard Rodríguez-Farré ◽  
Mercè Pallàs ◽  
Coral Sanfeliu
Keyword(s):  

Brain ◽  
2020 ◽  
Vol 143 (2) ◽  
pp. 390-392
Author(s):  
Maximilian Wiesmann ◽  
Frank-Erik de Leeuw

This scientific commentary refers to ‘Hippocampal vascular reserve associated with cognitive performance and hippocampal volume’, by Perosa et al. (doi: 10.1093/brain/awz383).


2019 ◽  
Vol 25 (7) ◽  
pp. 1027-1027
Author(s):  
Dena B. Dubal
Keyword(s):  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S619-S620
Author(s):  
Dorina Cadar ◽  
Lucy Stirland ◽  
Graciela Muniz Terrera

Abstract The close interlink between physical and mental health outcomes has long been recognised in gerontological research. Mental-physical comorbidities – the presence of at least one physical health long term condition, and at least one mental health-related long term condition are common in older age individuals. Numerous studies have shown a positive association between the prevalence of multimorbidity and age so, as the population of older individuals in developed nations continues to grow, multimorbidity is likely to become increasingly higher in ageing populations. A major goal in current gerontological neuropsychology and neuroepidemiological research is to better understand how interindividual differences in cognitive and mental health in old age emerge. Cognitive reserve (a marker of brain resilience) may come into play when facing stressors that affect cognitive decline and mental health, such as suffering from chronic diseases. We present data from three different longitudinal studies of ageing i) the Lothian Birth Cohort of 1921, ii) PREVENT and iii) the English Longitudinal Study of Ageing from the United Kingdom. These studies are ideally placed to address key research questions related to mental ageing, psychological health, terminal decline and their determinants. We explored the following objectives: 1) to investigate the association between an increasing number of chronic physical conditions, medication and mental disorders 2) to assess the role of childhood intelligence and education on the terminal decline in later life 3) to investigate the associations between different markers of cognitive reserve and dementia


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