scholarly journals Treadmill Exercise During Cerebral Hypoperfusion Has Only Limited Effects on Cognitive Function in Middle-Aged Subcortical Ischemic Vascular Dementia Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryo Ohtomo ◽  
Hidehiro Ishikawa ◽  
Keita Kinoshita ◽  
Kelly K. Chung ◽  
Gen Hamanaka ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Vascular Dementia ◽  
Treadmill Exercise ◽  
Basic Research ◽  
Cerebrovascular Diseases ◽  
Cerebral Hypoperfusion ◽  
Middle Aged ◽  
Age Related ◽  
Y Maze ◽  
Aging Populations

Clinical and basic research suggests that exercise is a safe behavioral intervention and is effective for improving cognitive function in cerebrovascular diseases, including subcortical ischemic vascular dementia (SIVD). However, most of the basic research uses young animals to assess the effects of exercise, although SIVD is an age-related disease. In this study, therefore, we used middle-aged mice to examine how treadmill exercise changes the cognitive function of SIVD mice. As a mouse model of SIVD, prolonged cerebral hypoperfusion was induced in 8-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into two groups: a group that received 6-week treadmill exercise and a sedentary group for observation. After subjecting the mice to multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to only be effective in ameliorating cognitive decline in the Y-maze test. We previously demonstrated that the same regimen of treadmill exercise was effective in young hypoperfused-SIVD mice for all three cognitive tests. Therefore, our study may indicate that treadmill exercise during cerebral hypoperfusion has only limited effects on cognitive function in aging populations.

scholarly journals Postural Hypotension and Cognitive Function in Older Adults

2017 ◽  
Vol 3 ◽  
pp. 233372141773321 ◽  
Author(s):  
Kenneth J. McLeod ◽  
Teesta Jain
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Soleus Muscle ◽  
Postural Hypotension ◽  
Cerebral Hypoperfusion ◽  
Muscle Stimulation ◽  
Cognitive Responses ◽  
Age Related ◽  
Quiet Sitting

Background: Cognitive decline in the elderly is associated with chronic cerebral hypoperfusion. While many forms of exercise can slow or reverse cognitive decline, compliance in unsupervised exercise programs is poor. Objective: We address whether passive exercise, that is, muscle stimulation, is capable of reversing postural hypotension in an older adult population sufficiently to significantly improve cognitive function as measured by executive function tests. Subjects and Methods: In this study, 50- to 80-year-old women underwent cognitive testing, long-duration cardiac hemodynamic recordings during quiet sitting, and 60 min of soleus muscle stimulation with continued hemodynamic recording. Results: Two thirds of our subjects were hypotensive (diastolic blood pressure [DBP] < 70 mmHg) after 30 min of quiet sitting. Cognitive performance was significantly better in individuals with higher DBPs (0.79 s per 1-mmHg increase in DBP). Soleus muscle stimulation resulted in an average increase in DBP of 6.1 mmHg, which could translate into a 30% or greater improvement in cognitive performance. Conclusions: Incongruent Stroop testing provides high statistical power for distinguishing differential cognitive responses to resting DBP levels. These results set the stage to investigate whether regular use of calf muscle pump stimulation could effectively reverse age-related cognitive impairment.

scholarly journals γ-Oryzanol Improves Cognitive Function and Modulates Hippocampal Proteome in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 753 ◽  
Author(s):  
Wiramon Rungratanawanich ◽  
Giovanna Cenini ◽  
Andrea Mastinu ◽  
Marc Sylvester ◽  
Anne Wilkening ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Function ◽  
Clinical Symptoms ◽  
Oryza Sativa L ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Age Related ◽  
Y Maze ◽  
Quantitative Changes

Rice (Oryza sativa L.) is the richest source of γ-oryzanol, a compound endowed with antioxidant and anti-inflammatory properties. γ-Oryzanol has been demonstrated to cross the blood-brain barrier in intact form and exert beneficial effects on brain function. This study aimed to clarify the effects of γ-oryzanol in the hippocampus in terms of cognitive function and protein expression. Adult mice were administered with γ-oryzanol 100 mg/kg or vehicle (control) once a day for 21 consecutive days following which cognitive behavior and hippocampal proteome were investigated. Cognitive tests using novel object recognition and Y-maze showed that long-term consumption of γ-oryzanol improves cognitive function in mice. To investigate the hippocampal proteome modulated by γ-oryzanol, 2D-difference gel electrophoresis (2D-DIGE) was performed. Interestingly, we found that γ-oryzanol modulates quantitative changes of proteins involved in synaptic plasticity and neuronal trafficking, neuroprotection and antioxidant activity, and mitochondria and energy metabolism. These findings suggested γ-oryzanol as a natural compound able to maintain and reinforce brain function. Although more intensive studies are needed, we propose γ-oryzanol as a putative dietary phytochemical for preserving brain reserve, the ability to tolerate age-related changes, thereby preventing clinical symptoms or signs of neurodegenerative diseases.

scholarly journals 672 COVID-19 Anxiety and Sleep in Middle-aged and Older Adults: Impact of Age and Sex

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A262-A263
Author(s):  
Sadhika Jagannathan ◽  
Mikayla Rodgers ◽  
Christina S McCrae ◽  
Mary Beth Miller ◽  
Ashley Curtis
Keyword(s):  
Older Adults ◽  
Sleep Quality ◽  
Sleep Duration ◽  
The United States ◽  
Sleep Efficiency ◽  
Middle Aged ◽  
Age Related ◽  
Aging Populations ◽  
Middle Aged Adults ◽  
Age And Sex

Abstract Introduction COVID-19 is an infectious respiratory illness that was declared a pandemic in March 2020. During the course of COVID-19, studies have demonstrated worsening sleep quality and anxiety. No studies have examined age-related and sex-specific associations between COVID-19 anxiety and sleep in aging populations. We examined associations between COVID-19 anxiety and sleep, and evaluated age and sex as moderators, in middle-aged/older adults. Methods Two hundred and seventy-seven middle-aged/older adults aged 50+ (Mage=64.68, SD=7.83; 44% women) living in the United States who were cognitively healthy (no cognitive impairment/dementia/neurological disorders) completed an online Qualtrics survey in July/August 2020 measuring sleep (Pittsburgh Sleep Quality Index; PSQI) and COVID-19 anxiety (Coronavirus Anxiety Scale; CAS). Multiple regressions examined whether CAS was independently associated with or interacted with age or sex in its associations with PSQI total score/subscores (sleep quality, sleep duration, sleep efficiency, daytime dysfunction), controlling for age, education, number of medical conditions, sleep/pain medication use, and COVID-19 status. Results CAS interacted with age (B=-.008, SE=.003 p=.02, R-squared=.02), not sex (p=.31), in its association with sleep duration. Higher CAS was associated with shorter sleep duration in oldest-older adults (~73 years old; B=.12, SE=.05, p=.01) and younger-older adults (~65 years old; B=.07, SE=.03, p=.02), not middle-aged adults (~57 years old, p=.47). CAS interacted with age (B=.01, SE=.004, p=.02), not sex (p=.56), in its association with sleep efficiency. Higher CAS was associated with worse sleep efficiency in oldest-older adults (B=.14, SE=.05, p=.009) and younger-older adults (B=.08, SE=.04, p=.03), not middle-aged adults (p=.60). Higher CAS was associated with greater daytime dysfunction (B=.26, SE=.07, p&lt;.001) and higher PSQI total score (B=.82, SE=.33, p=.01), and did not interact with age or sex (ps&gt;.05). Conclusion Increased COVID-19 anxiety is associated with several aspects of worse sleep (shorter sleep duration, sleep efficiency) in older adults but not middle-aged adults. Generally, in middle-aged/older adults, higher COVID-19 anxiety is associated with worse daytime dysfunction and overall sleep quality. Sex does not moderate these associations. Increased COVID-19 morbidity and mortality in aging populations may translate to increased anxiety and subsequent sleep disruptions. Interventions aimed at mitigating negative pandemic-related psychological and sleep outcomes may be particularly relevant for older adults. Support (if any):

Abstract P805: Inhibition of α5β1 Integrin as a Novel Therapeutic Approach in Experimental Vascular Dementia in Middle-Aged and Diabetic Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ifechukwude Joachim Biose ◽  
Amruta Narayanappa ◽  
Gregory J Bix
Keyword(s):  
White Matter ◽  
Vascular Dementia ◽  
Functional Outcome ◽  
Spontaneous Alternation ◽  
Integrin Expression ◽  
Diabetic Mice ◽  
Middle Aged ◽  
Y Maze ◽  
Α5β1 Integrin

Bilateral carotid artery stenosis (BCAS), a model of vascular dementia (VaD), causes cognitive impairment due to white matter injury and blood-brain barrier (BBB) disruption. Although risk factors for VaD such as Type-2 diabetes and aging are clinically relevant for therapeutic discovery, they are rarely studied. Recently, we determined that inhibition of brain α5β1 integrin with the peptide ATN-161 improves BBB stability and functional outcome after cerebral ischemia in mice. Also, after 14 days BCAS in mice, we showed increased brain α5β1 integrin expression which correlates with BBB disruption. We hypothesize that middle age and / or diabetes will intensify post-BCAS brain α5β1 integrin expression, contributing to worsened cerebrovascular pathology and cognitive decline, and that inhibition of α5β1 integrin with ATN-161 would reduce brain α5β1 integrin level, stabilize the BBB, attenuate brain-vascular pathology, and protect against VaD. Methods: BCAS was induced with titanium micro-coils (ID: 0.18 mm) in young and middle-aged C57B6/J (13-15 weeks old; n=57 and 57-63 weeks old; n=57, respectively) as well as in young 13-weeks old diabetic (B6.BKS(D)-Leprdb /- J, n=27; 35-56 g) and genotype control (B6.BKS(D)-Leprdb /+ J, n=27; 28-36 g) mice for 14, 32 and 60 days. After BCAS or sham surgery, mice were randomly assigned to ATN-161 (1 mg/kg, i.p., 3x /week) or saline groups. Functional outcome measures: Y-maze spontaneous alternation, novel object recognition and nesting tests were performed at baseline, post-BCAS days 14, 30, 48 & 60. Brain samples were assessed by immunofluorescence and western blot, for the expression of α5β1 integrin, tight junction proteins, as well as markers for white matter integrity, astrocyte and microglia activation. While the analysis of functional tests, brain histology and western blots are underway, we have thus-far determined that ATN-161 treatment reduces (p<0.01) BCAS-elevated brain α5β1 integrin to sham control levels and improves (p<0.001, compared to saline controls) Y-maze spontaneous alternation in young B6 mice after 14 days. We expect to demonstrate that inhibition of α5β1 with ATN-161 will improve cerebrovascular pathology and cognitive outcome following BCAS in middle-aged B6 and type-2 diabetic mice.

scholarly journals Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers

2021 ◽  
Vol 13 ◽  
Author(s):  
Sumonto Mitra ◽  
Giorgio Turconi ◽  
Taher Darreh-Shori ◽  
Kärt Mätlik ◽  
Matilde Aquilino ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cholinergic Neurons ◽  
Lewy Body Dementia ◽  
Cholinergic Transmission ◽  
Expression Of Genes ◽  
Age Related ◽  
Y Maze ◽  
In The Wild ◽  
And Function ◽  
Cholinergic Markers

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.

scholarly journals Preservation of Cognitive Function byLepidium meyenii(Maca) Is Associated with Improvement of Mitochondrial Activity and Upregulation of Autophagy-Related Proteins in Middle-Aged Mouse Cortex

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Shan-Shan Guo ◽  
Xiao-Fang Gao ◽  
Yan-Rong Gu ◽  
Zhong-Xiao Wan ◽  
A-Ming Lu ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Middle Aged ◽  
Aged Mice ◽  
Age Related ◽  
Mouse Cortex ◽  
Related Proteins ◽  
Age Related Cognitive Decline

Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline.

The Effect of Long-Term Environmental Enrichment in Chronic Cerebral Hypoperfusion-Induced Memory Impairment in Rats

2016 ◽  
Vol 19 (3) ◽  
pp. 278-286 ◽  
Author(s):  
Jong-Min Park ◽  
Ho-Hyun Seong ◽  
Han-Byeol Jin ◽  
Youn-Jung Kim
Keyword(s):  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Cognitive Functions ◽  
Environmental Enrichment ◽  
Nursing Intervention ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Vegf Expression ◽  
Y Maze

Vascular dementia (VaD) is the second most common cause of dementia. It occurs when the cerebral blood supply is reduced by disarrangement of the circulatory system. Environmental enrichment (EE) has been associated with cognitive improvement, motor function recovery, and anxiety relief with respect to various neurodegenerative diseases and emotional stress models. The purpose of this study was to determine whether long-term EE influenced cognitive impairment in a rat model of chronic hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (BCCAo). The Y-maze and Morris water maze tests were performed to evaluate the rats’ cognitive functions. Also, the protein expression of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP-calcium response element binding protein (pCREB), and vascular endothelial growth factor (VEGF) were confirmed by Western blot. The microvessels and angiogenesis-associated proteins in the hippocampal region were investigated using immunohistochemistry. The VaD + EE group showed significantly better cognitive functions than the VaD group in both the Y-maze and MWM tests. In addition, the VaD + EE group showed significantly increased expression of BDNF, pCREB, and VEGF in the hippocampus compared to the VaD group. Rats in the VaD + EE group also had increased length of microvessels and VEGF expression in the hippocampus. These results suggest that long-term EE exerts neuroprotective effects against cognitive impairment induced by chronic cerebral hypoperfusion through the enhancement of BDNF, pCREB, and VEGF expression and indicate that EE may be a good nursing intervention in vascular dementia patients.

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