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Neuropharmacology May 2018Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on... (Review)
Review
Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. This article is part of the Special Issue entitled 'Cerebral Ischemia'.
Topics: Animals; Dementia, Vascular; Humans; White Matter
PubMed: 29273521
DOI: 10.1016/j.neuropharm.2017.12.030 -
Journal of Cerebral Blood Flow and... Aug 2022Brain arteriolosclerosis (B-ASC) is characterized by pathologically altered brain parenchymal arterioles. B-ASC is associated with cognitive impairment and increased...
Brain arteriolosclerosis (B-ASC) is characterized by pathologically altered brain parenchymal arterioles. B-ASC is associated with cognitive impairment and increased likelihood of clinical dementia. To date, no study has been conducted on genome-wide genetic risk of autopsy-proven B-ASC. We performed a genome-wide association study (GWAS) of the B-ASC phenotype using multiple independent aged neuropathologic cohorts. Included in the study were participants with B-ASC autopsy and genotype data available from the NACC, ROSMAP, ADNI, and ACT data sets. Initial Stage 1 GWAS ( = 3382) and Stage 2 mega-analysis ( = 4569) were performed using data from the two largest cohorts (NACC and ROSMAP). Replication of top variants and additional Stage 3 mega-analysis were performed incorporating two smaller cohorts (ADNI and ACT). Lead variants in the top two loci in the Stage 2 mega-analysis (rs7902929, = ; rs2603462, = ) were significant in the ADNI cohort (rs7902929, = ; rs2603462, ). The rs2603462 lead variant colocalized with expression in the cerebellum (posterior probability = 90.1%). Suggestive associations were also found near and . We thus identified putative loci associated with B-ASC risk, but additional replication is needed.
Topics: Aged; Alzheimer Disease; Arteriolosclerosis; Brain; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide
PubMed: 35156446
DOI: 10.1177/0271678X211066299 -
Journal of Neurology Oct 2019Cerebral small vessel disease (CSVD) is a broad category of cerebrovascular diseases which primarily affect the perforating arterioles, capillaries and venules with... (Review)
Review
Cerebral small vessel disease (CSVD) is a broad category of cerebrovascular diseases which primarily affect the perforating arterioles, capillaries and venules with multiple distinct etiologies. In spite of distinctive pathogenesis, CSVD shares similar neuroimaging markers, including recent small subcortical infarct, lacune of presumed vascular origin, white matter hyperintensity of presumed vascular origin, perivascular space and cerebral microbleeds. The radiological features of neuroimaging markers are indicative for etiological analysis. Furthermore, in sporadic arteriosclerotic pathogenesis associated CSVD, the total CSVD burden is a significant predictor for stroke events, global cognitive impairment, psychiatric disorders and later life quality. This review aims to summarize the radiological characteristics as well as the clinical implication of CSVD markers and neuroimaging interpretation for CSVD symptomatology.
Topics: Cerebral Small Vessel Diseases; Glymphatic System; Humans; Intracranial Hemorrhages; Neuroimaging; White Matter
PubMed: 30291424
DOI: 10.1007/s00415-018-9077-3 -
Bratislavske Lekarske Listy 2001Arteriolosclerosis is a generalised systemic vascular disease which is characterised by hyalinisation of intima (hyalinosis) as well as proliferation and hypertrophy of... (Review)
Review
Arteriolosclerosis is a generalised systemic vascular disease which is characterised by hyalinisation of intima (hyalinosis) as well as proliferation and hypertrophy of the media in the arteriolar part of the arterial system (so-called benign arteriolosclerosis). However, the patients suffering from accelerated and malign hypertension develop also fibrinoid necrosis (so-called malign arteriolosclerosis, arteriolonecrosis). Arteriolosclerosis as well as other similar stenotic (obliterating, obstructive, occlusive) diseases of the arterial system, have one single common consequence--ischemia. Currently, angio-organic ischemic syndromes in the whole world most frequently result from atherosclerosis which, however, is not the only nosologic unit of the group of arterial diseases having the tendency to develop arterial wall sclerosis. The latter group is briefly referred to as arteriosclerosis. In addition to atherosclerosis, this group includes also Mönckeberg's medial arteriosclerosis, diabetic angiopathy and arteriolosclerosis. The authors of this study, on the basis of their analysis of their own large set of patients (71,662 angiologic consultant examinations performed during the period of 25 years of the existence of the Angiologic Department of the Medical Faculty Hospital of Comenius University in Bratislava) attract attention to the fact that the clinical picture of this disease is multiform, and that it occurs frequently in clinical practice. Therefore, angiology is a separate specialisation which is above the structure of internal medicine.
Topics: Arterioles; Arteriosclerosis; Humans
PubMed: 11725387
DOI: No ID Found -
Journal of the American Society of... Oct 2017Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level,... (Review)
Review
Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.
Topics: Aging; Humans; Kidney
PubMed: 28790143
DOI: 10.1681/ASN.2017040421 -
Klinicheskaia Laboratornaia Diagnostika Apr 2011Microangiopathy (MAP) in the distal arterial bed develops in the structures high in pericytes that have myofibrils and, by interacting with the endothelium, form the... (Review)
Review
Microangiopathy (MAP) in the distal arterial bed develops in the structures high in pericytes that have myofibrils and, by interacting with the endothelium, form the first peristaltic pumps; they push lymph, hemolymph and blood from the arterial bed to the venous one. The role of glucose, hyperglycemia, a glycation reaction and its end products in microvascular interstitial tissue damage in the arterial bed is shown only in the neuron axon terminals that surround the pool of the intercellular medium while the other axonal parts are present in the cerebrospinal fluid pool where hyperglycemia is absent. When glucose metabolism is activated through the poliolovic pathway, the endothelial cytosole accumulates organic osmolytes, such as sorbitol alcohol that, by causing hyperhydration, increases the height of endothelial cells. The decreased lumen of arterioles and capillaries enhances peripheral resistance to blood flow to give rise hypoperfusion and chronic hypoxia. Moreover, by bypassing the exchange capillaries and worsening cellular hypoperfusion and hypoxia in the paracrine communities, the arteriolo-venular shunt that releases blood into the venous bed functions, by getting around the exchange capillaries. Glucose metabolism activation through the hexosamine pathway generates glycotoxins, such as glyoxal and methylglyoxal. As bifunctional reagents, they interact with proteins simultaneously, by using both ends, form cross-links between the collagen fibers in the vascular interstitial matrix and irreversibly enhance the rigidity of arteriolar and capillary walls. As the rigidity of the walls is increased, the pericytes are unable to move blood along the capillaries, by worsening hypoperfusion and hypoxia. In diabetes, hyperglycemia becomes persistent and glycation increased. The conversion of collagen structured in the vascular wall to glycosylation end products and the impaired biological function of endoecology are a cause of a biological reaction of interstitial tissue inflammation. The obligate part of the biological reaction of inflammation is the oxidation by reactive oxygen species and the generation of malondialdehyde, that is also a bifunctional reagent. Fibroblast proliferation and arteriosclerosis are a result of MAP as a destructive inflammatory process in the arteriolar and capillary walls.
Topics: Animals; Arteries; Arteriolosclerosis; Atherosclerosis; Cell Communication; Diabetes Mellitus; Diabetic Angiopathies; Endothelium, Vascular; Humans; Hyperglycemia; Inflammation; Oxidative Stress
PubMed: 21739639
DOI: No ID Found -
Veterinary Pathology Sep 2019During a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of...
During a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of the testes was identified in several inbred strains. Lesions were limited to the testes and did not occur as part of any renal, systemic, or pulmonary arteriopathy or vasculitis phenotype. There was no evidence of systemic or pulmonary hypertension, and lesions did not occur in ovaries of females. Frequency was highest in males of the SM/J (27/30, 90%) and WSB/EiJ (19/26, 73%) strains, aged 383 to 847 days. Lesions were sporadically present in males from several other inbred strains at a much lower (<20%) frequency. The risk of testicular hyaline arteriolosclerosis is at least partially underpinned by a genetic predisposition that is not associated with other vascular lesions (including vasculitis), separating out the etiology of this form and site of arteriolosclerosis from other related conditions that often co-occur in other strains of mice and in humans. Because of their genetic uniformity and controlled dietary and environmental conditions, mice are an excellent model to dissect the pathogenesis of human disease conditions. In this study, a discrete genetically driven phenotype of testicular hyaline arteriolosclerosis in aging mice was identified. These observations open the possibility of identifying the underlying genetic variant(s) associated with the predisposition and therefore allowing future interrogation of the pathogenesis of this condition.
Topics: Aging; Animals; Arteriosclerosis; Female; Genetic Predisposition to Disease; Hyalin; Male; Mice; Mice, Inbred Strains; Rodent Diseases; Testicular Diseases; Testis
PubMed: 31060453
DOI: 10.1177/0300985819844822 -
Clinical and Experimental Nephrology Oct 2021
Topics: Arteriolosclerosis; Arteriosclerosis; Basement Membrane; Humans; Hyalin; Kidney Tubules; Kidney Tubules, Distal
PubMed: 34100167
DOI: 10.1007/s10157-021-02076-x -
Dermatology (Basel, Switzerland) 2018The histological characteristic of hypertensive leg ulcers (HLU) is the presence of "arteriolosclerosis." The pertinence of performing a skin biopsy to diagnose HLU is...
BACKGROUND
The histological characteristic of hypertensive leg ulcers (HLU) is the presence of "arteriolosclerosis." The pertinence of performing a skin biopsy to diagnose HLU is questionable, as cutaneous arteriolosclerosis may be related to patient comorbidities. The objective here was to evaluate the frequency of arteriolosclerosis in skin leg biopsies performed in patients without ulcer and in control patients with HLU.
METHODS
We performed a retrospective study between January 2013 and July 2014. Patients were included if they had undergone a deep skin biopsy on the lower limbs, in the absence of any leg ulcer. Controls were patients with typical HLU.
RESULTS
Fifty-eight patients and 6 controls were included. Hypertension was present in 25 patients (43%). Arteriolosclerosis, defined as fibrous endarteritis, was present in 35 out of 58 patients (60%) and in all of the controls. No hyalinosis or hyperplastic proliferative arteriolosclerosis was observed in the patients or controls. Only age was an independent factor associated with the presence of cutaneous arteriolosclerosis (p &x#3c; 0.0001).
CONCLUSION
Cutaneous arteriolosclerosis is significantly and independently associated with age. Thus, skin biopsy seems not to be necessary for the diagnosis of HLU but only for a differential diagnosis.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arteriolosclerosis; Biopsy; Case-Control Studies; Endarteritis; Female; Humans; Hypertension; Ischemia; Leg Ulcer; Male; Middle Aged; Retrospective Studies; Skin; Skin Diseases, Vascular
PubMed: 30199871
DOI: 10.1159/000492669 -
Acta Neuropathologica Feb 2023Arteriolosclerosis is common in older brains and related to cognitive and motor impairment. We compared the severity of arteriolosclerosis and its associations with...
Arteriolosclerosis is common in older brains and related to cognitive and motor impairment. We compared the severity of arteriolosclerosis and its associations with cerebrovascular disease risk factors (CVD-RFs) in multiple locations in the brain and spinal cord. Participants (n = 390) were recruited in the context of a longitudinal community-based clinical-pathological study, the Rush Memory and Aging Project. CVD-RFs were assessed annually for an average of 8.7 (SD = 4.3) years before death. The annual assessments included systolic (SBP) and diastolic (DBP) blood pressure, diabetes mellitus (DM), low- and high-density lipoprotein cholesterol, triglyceride, body mass index, and smoking. Postmortem pathological assessments included assessment of arteriolosclerosis severity using the same rating scale in three brain locations (basal ganglia, frontal, and parietal white matter regions) and four spinal cord levels (cervical, thoracic, lumbar and sacral levels). A single measure was used to summarize the severity of spinal arteriolosclerosis assessments at the four levels due to their high correlations. Average age at death was 91.5 (SD = 6.2) years, and 73% were women. Half showed arteriolosclerosis in frontal white matter and spinal cord followed by parietal white matter (38%) and basal ganglia (27%). The severity of arteriolosclerosis in all three brain locations showed mild-to-moderate correlations. By contrast, spinal arteriolosclerosis was associated with brain arteriolosclerosis only in frontal white matter. Higher DBP was associated with more severe arteriolosclerosis in all three brain locations. DM was associated with more severe arteriolosclerosis only in frontal white matter. Controlling for DBP, higher SBP was inversely associated with arteriolosclerosis in parietal white matter. Blood cholesterol and triglyceride, high body mass index, or smoking were not related to the severity of arteriolosclerosis in any brain region. None of the CVD-RFs were associated with the severity of spinal arteriolosclerosis. These data indicate that severity of arteriolosclerosis and its associations with CVD-RFs may vary in different CNS locations.
Topics: Humans; Female; Aged; Male; Independent Living; Arteriolosclerosis; Brain; Spinal Cord; Cerebrovascular Disorders; Risk Factors; Cholesterol; Triglycerides
PubMed: 36469116
DOI: 10.1007/s00401-022-02527-z