Vascular Atrophy Research Articles

Imatinib Sets Pericyte Mosaic in the Retina.

The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer’s, amyotrophic lateral sclerosis (ALS) and Parkinson’s. Platelet-derived growth factor receptors (PDGFRs) have been shown to be critical to PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood–retina barrier (BRB) were evaluated using blood albumin labeling. We found that imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers; this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of imatinib on PCs. Furthermore, blood–retina barrier disruption was not evident. In conclusion, our data suggest that imatinib could help in treating neurovascular diseases and serve as a model for PC loss, without BRB disruption.

CSF1R blockade induces macrophage ablation and results in mouse choroidal vascular atrophy and RPE disorganization.

The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular degeneration (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered that the ablation of choroidal macrophages via CSF1R blockade was associated with choroidal vascular atrophy and retinal pigment epithelial (RPE) changes including structural disruption, downregulation of visual cycle genes, and altered angiogenic factor expression. Suspending CSF1R blockade following ablation enabled spontaneous macrophage regeneration, which fully restored original macrophage distributions and morphologies. Macrophage regeneration was accompanied by arrested vascular degeneration and ameliorated pathological RPE alterations. These findings suggest that choroidal macrophages play a previously unappreciated trophic role in maintaining choroidal vasculature and RPE cells, implicating insufficiency in choroidal macrophage function as a factor in aging- and AMD-associated pathology. Modulating macrophage function may constitute a strategy for the therapeutic preservation of the choroid and RPE in age-related retinal disorders.

Co-overexpression of VEGF and GDNF in adipose-derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model.

ObjectivesTo evaluate the rapid repair potential of adipose‐derived stem cells (ADSCs) co‐overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it.Materials and methodsWe extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty‐six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC‐V), GDNF (ADSC‐G), or VEGF&GDNF (ADSC‐G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy.ResultsErectile function was almost recovered after 2 weeks of transplantation of ADSC‐G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC‐V or ADSC‐G. Moreover, GM‐ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves.ConclusionsThese promising data indicate that ADSCs co‐overexpressed VEGF and GDNF‐induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.

Carotid intima-media thickness relative to cognitive impairment in dialysis patients, and their relationship with brain volume and cerebral small vessel disease.

Background:Carotid intima–media thickness (cIMT) is considered a risk factor for and predictor of cerebrovascular disease. In this study, we explored the contribution of cIMT to cognitive impairment (CI) in dialysis patients and the role of cerebral small vascular disease (CSVD) and brain atrophy in this process.Methods:Cognitive function was assessed using a comprehensive cognitive test battery. CSVD and brain volume were assessed by magnetic resonance imaging, and cIMT was measured by ultrasonography. Multivariable analysis and mediation were used to explore the relevant relationships among cIMT, CI, CSVD and brain volume.Results:Seventy-three dialysis patients were enrolled. Approximately 54.8% were diagnosed with increased cIMT. The increased cIMT group was older and had lower serum albumin and creatinine levels than the normal cIMT group. There was no difference in the CSVD prevalence between the different cIMT groups. Patients in the normal, unilaterally and bilaterally increased cIMT subgroups demonstrated a gradual decrease in brain-matter volume and degenerate cognitive function. cIMT was related to cognitive function and gray-/white-matter volume. Increased cIMT was associated with a significantly increased risk of a reduced Mini Mental State Examination/Montreal Cognitive Assessment score and Trail A/B time delay. Mediation analysis showed that CI was mediated by brain-matter volume but not by CSVD.Conclusion:Increased cIMT was an independent risk factor for impairment of global cognitive function, memory, and executive function. The impact of cIMT on cognition was not induced by CSVD but by brain atrophy. cIMT may be a useful tool for screening patients at high risk of CI in the dialysis population.

Cognitive Correlates of MRI-defined Cerebral Vascular Injury and Atrophy in Elderly American Indians: The Strong Heart Study.

American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians. We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010-2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function. Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement. Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population.

Characterisation of vascular changes in different stages of Stargardt disease using double swept-source optical coherence tomography angiography

ObjectiveTo describe vascular changes in different stages of Stargardt disease (STGD) via double swept-source optical coherence tomography angiography.Methods and analysisProspective, cross-sectional case–control study. Twenty-three patients (45 eyes) with ABCA4 mutations...

P5745The Impact Of Brain Atrophy In The Young Patientwith Severe Heart Failure

Abstract Background Recently, several reports recognized the heart failure (HF) effected the brain impairment by impaired vascular blood flow and brain atrophy. However, there are no report mentioned the relationship brain atrophy and the mortality in young patient with severe HF. Methods A total 368 patients with severe HF form 2009 to 2014. We analyzed 117 patients aged under 55 years old without past history of cerebral artery disease. We evaluated the brain atrophy using head CT data by AZE VitualPlace and compared their clinical background, cardiac function, and the mortality. Results The mean age was 41±10 years (male 80%) and the average LVEF was 39±8%. The median follow-up period was 1.264 days. During the observations, we observed a total of 12 all cause death. The ROC analysis revealed that 10.2% of atrophy area was cut-off and the sensitivity was 80%, specificity was 69.5% and the area under the curve was 0.71. In univariate analysis, severe NYHA class, low LVEF, large brain atrophy (>10%) were significant factors as predictor of mortality (P<0.05). Interestingly, as a result of multiple analysis, only the large brain atrophy was independent predictor of mortality. Kaplan-Meier analysis resulted that the patients with the large brain atrophy as over 10% were statistically significant worse mortality than the other patients (P=0.02). Conclusion This is a first report to evaluate the brain atrophy area by CT in young severe HF patients. HF patients with ≥10% of brain atrophy have higher mortality.

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima–media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

Water soluble fractions of crude oil deteriorates water quality parameters and alters histopathological components of juvenile Clarias gariepinus

In this study, the water quality changes after the introduction of water soluble fractions of crude oil were monitored along-side the accompanying effects on histopathological changes in selected organs of juvenile Clarias gariepinus . After a preliminary short-term (96 hours) static toxicity tests, fish were exposed to four sub-lethal concentrations (30, 45, 60 and 75 % of the LC 50 corresponding to 67, 101, 135 and 169 mg/l respectively) and a control group containing clean water using a semi-static renewal method for 90 days. Water quality parameters, heavy metals and total petroleum hydrocarbon (TPH) were determined using standard methods. After the exposure period, liver, brain and gill were harvested, labeled and prepared for photomicrography. Chloride, conductivity, salinity, magnesium, biochemical oxygen demand, chemical oxygen demand, total dissolve solids, turbidity and nitrate levels increased significantly (p 0.05). Values of TPH increased (p<0.05) with increasing concentrations of the crude oil. All analysed heavy metals followed a direct proportional trend as their values increased (p<0.05) alongside concentrations. Several histopathological alterations were found in the liver (sinusoidal congestion, atrophy of hepatocytes, hepatocellular degeneration and diffuse coagulation necrosis of hepatocytes), brain (vascular congestion and atrophy of neurons, neuronal necrosis, gliosis and loss of neurons) and gill (moderate loss of the secondary gill lamellae, moderate lamellae atrophy and moderate diffuse lamellae hyperplasia). The intensity of these lesions increased with increase in exposure dose. Keywords: Toxicity, Petroleum, Heavy metals, Water quality, Organs, Clarias gariepinus , LC 50

Progressive Cerebral Ischemia and Intracerebral Hemorrhage after Indirect Revascularization for a Patient with Cerebral Proliferative Angiopathy

We previously reported a patient with cerebral proliferative angiopathy (CPA) who showed cerebral ischemia in resting and acetazolamide-stressed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123I-IMP-SPECT). At onset, the patient was treated conservatively. However, during the 2 years following initial onset, his hemiparesis and aphasia had gradually aggravated and his IQ scores were markedly decreased. MRI revealed progressive vascular proliferation and brain atrophy. 123I-IMP-SPECT showed more severely impaired cerebral blood flow (CBF) and cerebrovascular reactivity over the affected hemisphere. We performed an indirect revascularization to augment CBF; however, his neurological deficits were not improved and new arteriovenous shunts via extracranial-intracranial bypass were developed, followed by an asymptomatic small intracerebral hemorrhage.There are no reports on CPA patients who have shown cerebral hemorrhage after indirect revascularization. Treatments for CPA are still challenging and controversial. Cases with severe stenosis of the proximal arteries may benefit from indirect revascularization. But indirect bypass should not be indicated for such patients without main arterial stenosis, even if they have persistent ischemia.

Pathophysiology of chronic limb ischemia.

Chronic ischemia of the lower extremities is an everyday problem in vascular surgery clinics. In Germany, approximately 3% of all hospitalizations are due to peripheral artery disease (PAD), with critical limb ischemia (CLI) in particular showing a rapid increase. The consequences of chronic undersupply range from reduced walking distance to loss of limbs. At the beginning there are stress factors, such as hyperlipidemia (LDL), free radicals, arterial hypertension, infections or subclinical inflammation that interfere with endothelial homeostasis and cause endothelial dysfunction with increased permeability. Cells of the immune system are attracted and migrate into the vascular wall, where they lead to the degradation of matrix components and destabilization of the plaque. By changing the phenotype of smooth muscle cells and macrophages towards osteoclast-like cells, bone-like hardening of the vessel wall takes place. Above a vessel wall thickness of approximately 100 µm, hypoxia-induced factor (HIF-1α) is intensified by the lack of oxygen, which leads to an increase in growth factors, such as vascular endothelial growth factor (VEGF). This promotes angiogenesis, but it is not sufficient to compensate for a stenosed artery. Arteriogenesis refers to the growth of existing collateral vessels. The driving forces are the pressure gradient before and after the stenosis and the shear forces acting on the vessel walls. In the case of progressive stenosis, the compensatory capacities can be overtaxed and a manifest hypoxia in the tissue with regression of the obtained vascular structures and tissue atrophy occurs.

Histochemical characteristics of regressing vessels in the hyaloid vascular system of neonatal mice: Novel implication for vascular atrophy

The hyaloid vasculature constitutes a transitory system nourishing the internal structures of the developing eye, but the mechanism of vascular regression and its cell biological characteristics are not fully understood. The present study aimed to reveal the specificity of the hyaloid vessels by a systematic immunohistochemical approach for marker substances of myeloid cells and the extracellular matrix (ECM) in neonatal mice. Macrophages immunoreactive for F4/80, cathepsin D, and LYVE-1 gathered around the vasa hyaloidea propria (VHP), while small round cells in vascular lumen of VHP were selectively immunoreactive for galectin-3; their segmented nuclei and immunoreactivities for Ly-6G, CD11b, and myeloperoxidase indicated their neutrophilic origin. VHP possessed thick ECM and a dense pericyte envelope as demonstrated by immunostaining for laminin, type IV collagen, integrin β1, and NG2. The galectin-3+ cells loosely aggregated with numerous erythrocytes in the lumen of hyaloid vessels in a manner reminiscent of vascular congestion. Galectin-3 is known to polymerize and form a complex with ECM and NG2 as well as recruit leukocytes on the endothelium. Observation of galectin-3 KO mice implicated the involvement of galectin-3 in the regression of hyaloid vasculature. Since macrophages may play central roles including blocking of the blood flow and the induction of apoptosis in the regression, galectin-3+ neutrophils may play a supportive role in the macrophage-mediated involution of the hyaloid vascular system.

THE IMPACT OF BRAIN ATROPHY IN THE YOUNG PATIENT WITH SEVERE HEART FAILURE

Recently, several reports recognized the heart failure(HF) effected the brain impairment by impaired vascular blood flow and brain atrophy. However, there are no report mentioned the relationship brain atrophy and the mortality in young patient with severe HF. A total 368 patients with severe HF

Telomere Length and Magnetic Resonance Imaging Findings of Vascular Brain Injury and Central Brain Atrophy: The Strong Heart Study.

Telomeres are repeating regions of DNA that cap chromosomes. They shorten over the mammalian life span, especially in the presence of oxidative stress and inflammation. Telomeres may play a direct role in cell senescence, serving as markers of premature vascular aging. Leukocyte telomere length (LTL) may be associated with premature vascular brain injury and cerebral atrophy. However, reports have been inconsistent, especially among minority populations with a heavy burden of illness related to vascular aging. We examined associations between LTL and magnetic resonance imaging in 363 American Indians aged 64-93 years from the Strong Heart Study (1989-1991) and its ancillary study, Cerebrovascular Disease and Its Consequences in American Indians (2010-2013). Our results showed significant associations of LTL with ventricular enlargement and the presence of white matter hyperintensities. Secondary models indicated that renal function may mediate these associations, although small case numbers limited inference. Hypertension and diabetes showed little evidence of effect modification. Results were most extreme among participants who evinced the largest decline in LTL. Although this study was limited to cross-sectional comparisons, it represents (to our knowledge) the first consideration of associations between telomere length and brain aging in American Indians. Findings suggest a relationship between vascular aging by cell senescence and severity of brain disease.

Is the 1298A>C polymorphism in the MTHFR gene a risk factor for arterial ischaemic stroke in children? The results of meta-analysis

An elevated level of homocysteine is a risk factor for vascular diseases, brain atrophy and several other disorders. The 1298A>C polymorphism (rs1801131) leads to mildly decreased MTHFR activity. Previously, it was observed that the MTHFR 1298A>C polymorphism in combined analysis with the MTHFR 677C>T polymorphism increases homocysteine levels. However, conflicting results on its relation to ischaemic stroke in children can be found. We conducted a meta-analysis to analyse possible connections between the MTHFR 1298A>C polymorphism and ischaemic stroke in paediatric patients. We identified available data published before December 2016 using appropriate keywords and searching PubMed as well as the references cited in the found articles. Eight case–control studies were included in the meta-analysis (426 children with stroke and 778 controls). Statistical analyses were made using R and Comprehensive Meta-Analysis softwares to investigate the impact of polymorphism in four models: dominant, recessive, additive and allelic. No publication bias was observed in the meta-analysis. We demonstrated no relationship between the 1298A>C polymorphism and ischaemic stroke in children in the case of recessive, additive and allelic models. However, the results of the dominant model analysis should be treated with caution due to the sensitivity analysis results. After omitting one of the included study, we observed a significant association between the carriers of the MTHFR C allele (cases with AC + CC genotypes) and ischaemic stroke in children (OR 1.35 95% CI 1.02–1.79, p = 0.035 in a fixed effects model). In conclusion, the 1298A>C polymorphism in the MTHFR gene is not a risk factor for ischaemic stroke in paediatric patients.

Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study

Background: The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. Methods: Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. Results: The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. Conclusions: Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population.

Neuropsychiatric Symptom Clusters in Stroke and Transient Ischemic Attack by Cognitive Status and Stroke Subtype: Frequency and Relationships with Vascular Lesions, Brain Atrophy and Amyloid.

BackgroundThe objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters.MethodsHospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3–6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer’s Disease (AD) pathology.Results50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention.ConclusionFrequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.

Regional Blood Flow Characteristics in Response to Maximal Voluntary Contractions are Attenuated in Stroke Patients.

Individuals with stroke have difficulty sustaining or generating forces in their leg muscles. Currently, the mechanisms underlying these force deficits are not fully understood. The contribution of blood flow patterns to isolated muscle function in stroke patients is not completely understood but it can be speculated that abnormalities exist in the presence of vascular disease and muscle atrophy due to stroke. Near infrared spectroscopy devices measure regional oxygen saturations (rSO2) and provide a global assessment of regional blood flow. PURPOSE: We sought to evaluate the regulation of blood flow to the exercising muscle during maximal voluntary contractions (MVC) in patients having suffered a stroke compared to healthy controls. METHODS: A pilot investigation of 5 patients having suffered a stroke and 5 controls was performed to assess regional flow patterns via NIRS during MVC with the leg at 90 degrees (Biodex: Shirley, New York). The dominant leg of controls as well as both paretic and non-paretic legs in patients were tested. NIRS values were used to evaluate regional flow in the rectus femoris and reported as a high, low, and percent change during the MVC effort. RESULTS: Control subjects had a greater peak torque (241.8 ± 32.2 Nm) when compared to the non-paretic leg (87.4 ± 24.8Nm) or paretic leg (59.4 ± 31.4 Nm) of the patients with stroke (ANOVA, p<0.001). The rSO2 prior to MVC did not differ significantly between groups, however there was a robust desaturation noted in the controls (-30.8 ± 17.9 % decline) that was significantly beyond that appreciated in either the non-paretic (-5.9 ± 8.11 % decline) or paretic leg (-5.2 ± 7.7 % decline) of the stroke patients (ANOVA, p=0.01). A linear relationship exist between MVC and percent change in rSO2 for the control group (r= .929, P=0.023) that did not exist in either the non-paretic or paretic leg of the stroke patients. CONCLUSIONS: Individuals having suffered from a stroke have an attenuated blood flow response as assessed by NIRS monitoring during a MVC maneuver. These findings are not isolated to the paretic leg but exist equally in the non-paretic limb suggesting the potential of global perfusion issues in the patients having suffered a stroke. Further investigation into the mechanisms behind these improvements and the impact on leg function is warranted.

Abstract TP453: Physical Inactivity Associated With Vascular Depression or Apathy Leads to Hippocampal Atrophy and Memory Dysfunction in Community-dwelling Elderly Subjects: The Sefuri Study

Background and Purpose: Vascular depression has negative effects on physical activity, which is a robust preventive factor against Alzheimer's disease or hippocampal atrophy. Therefore, we investigated the relationship among vascular depression (i.e., apathy associated with deep white matter lesions [DWMLs]), physical activity, hippocampal atrophy, and memory function using structural equation modeling (SEM). Subjects and Methods: We examined 213 non-demented elderly subjects without clinically apparent depression. All participants underwent Mini-Mental State Examination, Rivermead Behavioral Memory Test [RBMT] for episodic long-term memory, and a visual analogue version of the Starkstein’s apathy scale (Yao et al., Hypertens Res 2009;32:586). Physical activities were assessed with a questionnaire consisted of 3 components: leisure-time, work, and sport activities (Baecke et al., Am J Clin Nutr 1982;36:936). We evaluated the degree of hippocampal atrophy, using a software program the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD advance) based on SPM8 plus DARTEL (Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra). Results: When possible confounders were entered into the logistic regression model, the independent predictors of hippocampal atrophy (the highest quintile of VSRAD z-score) were age (OR per 10 years 3.257, 95%CI 1.988-5.338), and leisure-time physical activity (OR per 1-point 0.810, 95%CI 0.707-0.928). Path analysis based on SEM indicated that the direct paths from DWMLs to apathy (β= -0.18, p&lt;0.01) and from apathy to leisure-time activity (β= 0.23, p&lt;0.001) were significant. Furthermore, the direct paths from leisure-time activity to hippocampal atrophy (β= -0.18, p&lt;0.01) and from hippocampal atrophy to memory dysfunction (RBMT) (β= -0.26, p&lt;0.001) were significant. The presented model reasonably fit the data: goodness of fit index = 0.97, adjusted goodness of fit index = 0.93, comparative fit index = 0.97, and root mean square error of approximation = 0.04. Conclusions: Based on the present SEM analysis, we propose a hypothesis that physical inactivity associated with vascular depression would lead to hippocampal atrophy or Alzheimer’s disease.

Exercise, cognitive function, and aging.

Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise.