Vascular Contributions to Brain Health: Cross-Cutting Themes

Stroke ◽  
2022 ◽  
Author(s):  
Steven M. Greenberg
Keyword(s):  
Successful Aging ◽  
Potential Role ◽  
Brain Health ◽  
Ethical Imperative ◽  
Small Vessels ◽  
Age Related ◽  
Brain Recovery ◽  
Recovery Mechanisms ◽  
Epidemiologic Risk ◽  
Pathophysiologic Mechanisms

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging—and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: 1) the lifetime course of vascular brain injury pathogenesis and progression; 2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; 3) the need for improved tools to study the cerebral small vessels themselves; 4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and 5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

2021 ◽  
Author(s):  
Silvia Migliaccio ◽  
Viviana M Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Clara Crescioli ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease ◽  
Cardio Vascular

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 44
Author(s):  
Silvia Migliaccio ◽  
Viviana M. Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Andrea Lenzi ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, which could facilitate the development of interventions contributing to “successful aging” and improving quality of life. Cardiovascular diseases (CVD) include pathologies affecting the heart or blood vessels, such as hypertension, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations that raise the risk of CVD development. Several factors have been reported to play a role in the alterations observed in muscle and endothelial cells and that lead to increased CVD, such as genetic pattern, smoking and unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the past decades attention has been focused on a potential role of several pollutants that disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatous degeneration process and CVD progression.

scholarly journals Bone Morphogenetic Proteins and Diabetic Retinopathy

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 593
Author(s):  
Khaled Elmasry ◽  
Samar Habib ◽  
Mohamed Moustafa ◽  
Mohamed Al-Shabrawey
Keyword(s):  
Diabetic Retinopathy ◽  
Bone Morphogenetic Proteins ◽  
Potential Role ◽  
Microvascular Dysfunction ◽  
Cardiovascular Complications ◽  
Bmp Signaling ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Inflammation ◽  
Underlying Mechanisms

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

scholarly journals Gene Expression Profile in Different Age Groups and Its Association with Cognitive Function in Healthy Malay Adults in Malaysia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1611
Author(s):  
Nur Fathiah Abdul Abdul Sani ◽  
Ahmad Imran Zaydi Amir Amir Hamzah ◽  
Zulzikry Hafiz Abu Abu Bakar ◽  
Yasmin Anum Mohd Mohd Yusof ◽  
Suzana Makpol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Successful Aging ◽  
Expression Patterns ◽  
Age Groups ◽  
Genetic Network ◽  
Cross Sectional ◽  
Age Related ◽  
Age Related Cognitive Decline

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.

Older Parents’ and Middle-Aged Children’s Communication as Predictors of Children’s Successful Aging

2018 ◽  
Vol 38 (3) ◽  
pp. 305-328 ◽  
Author(s):  
Quinten S. Bernhold
Keyword(s):  
Path Analysis ◽  
Successful Aging ◽  
Aging Process ◽  
Family Members ◽  
Middle Aged ◽  
Older Parents ◽  
Subjective Perceptions ◽  
Age Related ◽  
Language And Communication

The communicative ecology model of successful aging (CEMSA) examines how people’s language and communication surrounding the aging process (e.g., making age-related excuses) predicts successful aging. Using the CEMSA, this study examined how middle-aged U.S. American children’s and their parents’ age-related communication predicts children’s subjective perceptions of their own successful aging, via children’s aging efficacy. Three communication profiles emerged for children and their parents, namely engaged, bantering, and disengaged agers. Path analysis revealed that parents’ age-related communication predicted children’s successful aging, via children’s aging efficacy. Relative to children with disengaged parents, children with bantering parents were more likely to be efficacious with respect to their aging, which in turn positively predicted successful aging. The language and communication people observe from older family members may be consequential in shaping their aging trajectories for the better or worse.

scholarly journals Transcriptional profiling predicts running promotes cerebrovascular remodeling in young but not midlife mice

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Kate E. Foley ◽  
Hongtian Stanley Yang ◽  
Leah C. Graham ◽  
Gareth R. Howell
Keyword(s):  
Cognitive Decline ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Brain Health ◽  
New Approach ◽  
Age Related ◽  
Voluntary Running ◽  
Differential Gene ◽  
Age Related Cognitive Decline ◽  
Potential Therapeutic Intervention

Abstract Background The incidence of dementia and cognitive decline is increasing with no therapy or cure. One of the reasons treatment remains elusive is because there are various pathologies that contribute to age-related cognitive decline. Specifically, with Alzheimer’s disease, targeting to reduce amyloid beta plaques and phosphorylated tau aggregates in clinical trials has not yielded results to slow symptomology, suggesting a new approach is needed. Interestingly, exercise has been proposed as a potential therapeutic intervention to improve brain health and reduce the risk for dementia, however the benefits throughout aging are not well understood. Results To better understand the effects of exercise, we preformed transcriptional profiling on young (1–2 months) and midlife (12 months) C57BL/6 J (B6) male mice after 12 weeks of voluntary running. Data was compared to age-matched sedentary controls. Interestingly, the midlife running group naturally broke into two cohorts based on distance ran - either running a lot and more intensely (high runners) or running less and less intensely (low runners). Midlife high runners had lower LDL cholesterol as well as lower adiposity (%fat) compared to sedentary, than midlife low runners compared to sedentary suggesting more intense running lowered systemic markers of risk for age-related diseases including dementias. Differential gene analysis of transcriptional profiles generated from the cortex and hippocampus showed thousands of differentially expressed (DE) genes when comparing young runners to sedentary controls. However, only a few hundred genes were DE comparing either midlife high runners or midlife low runners to midlife sedentary controls. This indicates that, in our study, the effects of running are reduced through aging. Gene set enrichment analyses identified enrichment of genes involved in extracellular matrix (ECM), vascular remodeling and angiogenesis in young runners but not midlife runners. These genes are known to be expressed in multiple vascular-related cell types including astrocytes, endothelial cells, pericytes and smooth muscle cells. Conclusions Taken together these results suggest running may best serve as a preventative measure to reduce risk for cerebrovascular decline. Ultimately, this work shows that exercise may be more effective to prevent dementia if introduced at younger ages.

scholarly journals An epigenetic predictor of death captures multi-modal measures of brain health

2019 ◽  
Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Simon R. Cox ◽  
Daniel L. McCartney ◽  
Sarah E. Harris ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Epigenetic Mechanism ◽  
Vascular Lesions ◽  
Epigenetic Clock ◽  
General Cognitive Ability ◽  
Brain Health ◽  
Standard Deviation Increase ◽  
Brain White Matter ◽  
Age Related ◽  
Lothian Birth Cohort

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm) – a commonly studied epigenetic mechanism. A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as a number of age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n=709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over twelve years of follow-up (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β=-0.11), lower age 73 general cognitive ability (β=-0.18), decreased brain volume (β=-0.25) and increased brain white matter hyperintensities (β=0.17). Sixty-eight of 137 health- and brain-related phenotypes tested were significantly associated with DNAm GrimAge. Adjusting all models for childhood cognitive ability attenuated to non-significance a small number of associations (12/68 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge cross-sectionally associates with lower cognitive ability and brain vascular lesions in older age, independently of early life cognitive ability. Thus, this epigenetic predictor of mortality is also associated with multiple different measures of brain health and may aid in the prediction of age-related cognitive decline.

scholarly journals Recovery of Apraxia of Speech and Aphasia in Patients With Hand Motor Impairment After Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Helena Hybbinette ◽  
Ellika Schalling ◽  
Jeanette Plantin ◽  
Catharina Nygren-Deboussard ◽  
Marika Schütz ◽  
...  
Keyword(s):  
Left Hemisphere ◽  
Motor Impairment ◽  
Stroke Recovery ◽  
Similar Amount ◽  
Apraxia Of Speech ◽  
Stroke Patients ◽  
Post Stroke ◽  
Language Functions ◽  
Brain Recovery ◽  
Recovery Mechanisms

Objective: Aphasia and apraxia of speech (AOS) after stroke frequently co-occur with a hand motor impairment but few studies have investigated stroke recovery across motor and speech-language domains. In this study, we set out to test the shared recovery hypothesis. We aimed to (1) describe the prevalence of AOS and aphasia in subacute stroke patients with a hand motor impairment and (2) to compare recovery across speech-language and hand motor domains. In addition, we also explored factors predicting recovery from AOS.Methods: Seventy participants with mild to severe paresis in the upper extremity were assessed; 50% of these (n = 35) had left hemisphere (LH) lesions. Aphasia, AOS and hand motor assessments and magnetic resonance imaging were conducted at 4 weeks (A1) and at 6 months (A2) after stroke onset. Recovery was characterized in 15 participants showing initial aphasia that also had complete follow-up data at 6 months.Results: All participants with AOS and/or aphasia had LH lesions. In LH lesioned, the prevalence of aphasia was 71% and of AOS 57%. All participants with AOS had aphasia; 80% of the participants with aphasia also had AOS. Recovery in aphasia (n = 15) and AOS (n = 12) followed a parallel pattern to that observed in hand motor impairment and recovery correlated positively across speech-language and motor domains. The majority of participants with severe initial aphasia and AOS showed a limited but similar amount of recovery across domains. Lesion volume did not correlate with results from behavioral assessments, nor with recovery. The initial aphasia score was the strongest predictor of AOS recovery.Conclusion: Our findings confirm the common occurrence of AOS and aphasia in left hemisphere stroke patients with a hand motor impairment. Recovery was similar across speech-language and motor domains, even in patients with severe impairment, supporting the shared recovery hypothesis and that similar brain recovery mechanisms are involved in speech-language and motor recovery post stroke. These observations contribute to the knowledge of AOS and its relation to motor and language functions and add information that may serve as a basis for future studies of post stroke recovery. Studies including neuroimaging and/or biological assays are required to gain further knowledge on shared brain recovery mechanisms.

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