Neurodegenerative disorders in older people

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0061 ◽

2020 ◽

pp. 601-611

Author(s):

John Hindle

Keyword(s):

Risk Factors ◽

Older People ◽

Protective Factors ◽

Genetic Susceptibility ◽

Neurodegenerative Disorders ◽

Neuronal Death ◽

Clinical Signs ◽

Symptomatic Treatment ◽

Structure And Function ◽

And Function

Neurodegenerative disorders are associated with a progressive loss of structure and function of neurones that leads to neuronal death. Their aetiology combines ageing, genetic susceptibility, and risk factors including environmental exposure, balanced against protective factors. They present with varying combinations of progressive cognitive, emotional, motor, autonomic and peripheral symptoms, and clinical signs. Neurodegenerative conditions are all likely to have a preclinical prodromal period, followed by slow initial decline during which there is clinical presentation, followed by a further steady decline and an eventual accelerated decline. The rate of progression of these disorders varies greatly, but they are all inevitably progressive, currently have no cure, and require symptomatic treatment.

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The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

The Oxford Handbook of Adult Cognitive Disorders ◽

10.1093/oxfordhb/9780190664121.013.27 ◽

2019 ◽

pp. 574-599

Author(s):

Victoria J. Williams ◽

Steven E. Arnold ◽

David H. Salat

Keyword(s):

Risk Factors ◽

Cognitive Impairment ◽

Cerebrovascular Disease ◽

Cognitive Decline ◽

Vascular Dementia ◽

Structure And Function ◽

Vascular Risk Factors ◽

Vascular Health ◽

Vascular Risk ◽

And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

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Deubiquitylating enzymes in neuronal health and disease

Cell Death and Disease ◽

10.1038/s41419-020-03361-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fatima Amer-Sarsour ◽

Alina Kordonsky ◽

Yevgeny Berdichevsky ◽

Gali Prag ◽

Avraham Ashkenazi

Keyword(s):

Human Brain ◽

Neurodegenerative Disorders ◽

Structure And Function ◽

Pivotal Role ◽

Protein Homeostasis ◽

Neuronal Function ◽

Health And Disease ◽

And Function

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.

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Normal Thyroid Structure and Function in Rhophilin 2-Deficient Mice

Molecular and Cellular Biology ◽

10.1128/mcb.25.7.2846-2852.2005 ◽

2005 ◽

Vol 25 (7) ◽

pp. 2846-2852 ◽

Cited By ~ 8

Author(s):

Jens Behrends ◽

Serge Clément ◽

Bernard Pajak ◽

Viviane Pohl ◽

Carine Maenhaut ◽

...

Keyword(s):

Rho Gtpase ◽

Clinical Signs ◽

Structure And Function ◽

Secretory Process ◽

Thyroid Cell ◽

Thyroid Cells ◽

Thyroid Cell Culture ◽

And Function ◽

Deficient Mice ◽

Stimulation Of

ABSTRACT Rhophilin 2 is a Rho GTPase binding protein initially isolated by differential screening of a chronically thyrotropin (TSH)-stimulated dog thyroid cDNA library. In thyroid cell culture, expression of rhophilin 2 mRNA and protein is enhanced following TSH stimulation of the cyclic AMP (cAMP) transduction cascade. Yeast two-hybrid screening and coimmunoprecipitation have revealed that the GTP-bound form of RhoB and components of the cytoskeleton are protein partners of rhophilin 2. These results led us to suggest that rhophilin 2 could play an important role downstream of RhoB in the control of endocytosis during the thyroid secretory process which follows stimulation of the TSH/cAMP pathway. To validate this hypothesis, we generated rhophilin 2-deficient mice and analyzed their thyroid structure and function. Mice lacking rhophilin 2 develop normally, have normal life spans, and are fertile. They have no visible goiter and no obvious clinical signs of hyper- or hypothyroidism. The morphology of thyroid cells and follicles in these mice were normal, as were the different biological tests performed to investigate thyroid function. Our results indicate that rhophilin 2 does not play an essential role in thyroid physiology.

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Abstract P124: Neighborhood Density of Hispanic/Latinos and Left Ventricular Structure: ECHO-SOL and SOL-CASAS

Circulation ◽

10.1161/circ.137.suppl_1.p124 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Sonia Ponce ◽

Matthew A Allison ◽

Jordan A Carlson ◽

Krista M Perreira ◽

Matthew S Loop ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Left Ventricular ◽

Structure And Function ◽

Ethnic Density ◽

Ventricular Structure ◽

Hispanic Latinos ◽

And Function

Introduction: Heart failure represents a significant public health problem because of increasing prevalence and lack of effective medical treatment. Hispanic/Latinos have a high burden of cardio-metabolic comorbidities and adverse socioeconomic conditions that place them at risk for heart failure. However, some literature indicates that among Hispanics/Latinos, residing in areas with high Hispanic/Latino ethnic density is associated with better health outcomes. There is a paucity of data on the effect of Hispanic/Latino ethnic density and risk markers for heart failure. Therefore, we evaluated the association between Hispanic/Latino ethnic concentration and several echocardiographic measures of left ventricular structure and function. Methods: Data on baseline characteristics from the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL), echocardiographic measures of cardiac structure and function (ECHO-SOL), and neighborhood Hispanic/Latino ethnic density (San Diego SOL-CASAS) were analyzed. Hispanic/Latino ethnic density was calculated for each person based on an 800-m buffer around their home. Hispanic/Latino ethnic density was then calculated using data from the 2010 Census as the percent of Hispanic/Latinos divided by the total population at the Census block level and calculating an average value for all Census blocks that overlapped with the participant's address. Multivariable linear regression analysis adjusting for personal demographics and cardiovascular risk factors was conducted. Results: A total of 350 participants with data from all three databases were included in the analysis. The mean age was 55±7 years, 69% were female, and 26%, 38%, and 43% had diabetes, hypertension, and dyslipidemia, respectively. Thirty-six percent had less than high school education, and 58% were low income. In models adjusting for age, sex, education level, income, acculturation, and cardiovascular risk factors, a 1-percent higher Hispanic/Latino ethnic density was associated with lower left ventricular mass (0.47, p-value = 0.02). Other echocardiographic measures of cardiac structure and function were not significantly related to Hispanic/Latino ethnic density. Conclusion: Higher Hispanic/Latino ethnic density was associated with lower LVM independent of personal SES and common cardiovascular risk factors. These findings suggest that Hispanic/Latinos residing in areas with higher Hispanic/Latino ethnic density might have a lower risk of future HF. However, further research to understand the specific factors that mediate the observed associations are necessary.

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Effect of wheelchair-modified rowing exercise on cardiometabolic risk factors in spinal cord injured wheelchair users: protocol for a randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-040727 ◽

2020 ◽

Vol 10 (10) ◽

pp. e040727

Author(s):

Rasmus Kopp Hansen ◽

Afshin Samani ◽

Uffe Laessoe ◽

Aase Handberg ◽

Ryan Godsk Larsen

Keyword(s):

Risk Factors ◽

Cardiometabolic Risk ◽

Controlled Trial ◽

Structure And Function ◽

Cardiometabolic Risk Factors ◽

Upper Body ◽

Vascular Structure ◽

Wheelchair Users ◽

Randomised Controlled ◽

And Function

IntroductionCardiovascular and metabolic diseases are a growing concern for individuals with spinal cord injury (SCI). Physical inactivity contributes to cardiometabolic morbidity and mortality in the SCI population. However, previous studies have shown mixed results regarding the effects of exercise on cardiometabolic risk factors in individuals with SCI. This discrepancy could be influenced by insufficient exercise stimuli. Recent guidelines recommend 30 min of moderate-to-vigorous intensity aerobic exercise, three times per week, for improvement in cardiometabolic health in individuals with SCI. However, to date, no studies have implemented an exercise intervention matching the new recommendations to examine the effects on cardiometabolic risk factors. Therefore, the primary objective of this study is to determine the effects of 12 weeks of wheelchair user-modified upper-body rowing exercise on both traditional (constituents of the metabolic syndrome) and novel (eg, vascular structure and function) cardiometabolic risk factors in manual wheelchair users with SCI.Methods and analysisA randomised controlled trial will compare 12 weeks of upper-body rowing exercise, 30 min three times per week, with a control group continuing their normal lifestyle. Outcome measurements will be performed immediately before (baseline), after 6 weeks (halfway), 12 weeks of training (post) and 6 months after the termination of the intervention period (follow-up). Outcomes will include inflammatory (eg, C reactive protein) and metabolic biomarkers determined from venous blood (with serum fasting insulin as primary outcome), body composition, arterial blood pressure, cardiorespiratory fitness level, brachial artery vascular structure and function and autonomic nervous system function.Ethics and disseminationThis trial is reported to the Danish Data Protection Agency (J.nr. 2019-899/10-0406) and approved by the Committees on Health Research Ethics in The North Denmark Region on 12 December 2019 (J.nr. N-20190053). The principal investigator will collect written informed consent from all participants prior to inclusion. Irrespective of study outcomes, the results will be submitted to peer-reviewed scientific journals for publication.Trial registration numberNCT04390087.

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