Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subcortical ischemic vascular dementia (SIVD) is a main subgroup of vascular dementia related to cerebral small vessel disease. Risk factors for SIVD include hypertension, ageing, and diabetes mellitus, but the specific contribution of each factor to the development of cerebral small vessel disease remains obscure. This is mainly because SIVD in the elderly might be affected by many factors related to the ageing process. Hereditary cerebral small vessel diseases, including cerebral autosomal-dominant or autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL or CARASIL) and cerebral amyloid angiopathy, are affected by different pathomechanisms, but these diseases indicate a clear a role of the cerebral small vessel on subcortical dementia. CADASIL is caused by a cysteine residue-related mutation in the EGF-like repeat on the extracellular domain of Notch3. Pathological examination of a CADASIL brain indicated abnormal accumulation of the extracellular domain of Notch3 with extracellular matrix proteins, including tissue inhibitor of metalloproteinase 3 and vitronectin, around vascular smooth muscle cells. CARASIL is caused by a mutation in HTAR1, a serine protease that regulates transforming growth factor (TGF)-beta signaling. The mutation in HTAR1 related to CARASIL fails to repress TGF-beta signaling and induces the accumulation of extracellular matrix, including the extra domain-A region of fibronectin and versican. The individual and common pathomechanisms of hereditary cerebral small vessel disease are discussed in this review.
...
PMID:[Subcortical ischemic vascular dementia: lesson from hereditary cerebral small vessel disease]. 2584 89

The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the 'ageing brain'. These include angiopathies (affecting both large and small arteries) that result from 'classical' risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD - though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects of CVD may include neuroinflammation and biochemical 'lesions' that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change - commonly seen in the brains of geriatric subjects - remains controversial. In recent years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL, Trex1-related microangiopathies, CARASAL, familial forms of cerebral amyloid angiopathy or CAA) have provided interesting cellular and molecular clues to the pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD-related CAA.
 ...
PMID:Review: Vascular dementia: clinicopathologic and genetic considerations. 2938 Sep 13

Hereditary types of ischemic cerebral subcortical small vessel disease (SSVD) are rare, usually autosomal dominant, diseases, due to an abnormality in vessel wall synthesis. They may present with various combinations of migraine with aura, ischemic events (transient ischemic attacks, lacunar strokes) and progressively worsening ischemic lesion load in brain imaging. Eventually, vascular cognitive impairment (usually of the frontal-subcortical type) develops, frequently accompanied by behavioral-psychiatric symptoms and bilateral pyramidal and pseudobulbar signs leading to severe disability and premature death. In some patients, microbleeds and hemorrhagic strokes may be present. Despite their rarity, these disorders offer a statistically homogeneous population (usually without additional pathology such as Alzheimer's disease), suitable for the study of vascular cognitive impairment. The few studies on the relative frequency of these disorders indicate that the most frequent (or rather the least rare), accounting for more than half of patients, is CADASIL, due to mutations of the NOTCH3 gene, followed by COL4A1/A2-related disease, autosomal dominant forms of HTRA1-related disease and leucoencephalopathies with calcifications and cysts. Mutations of TREX1, GLA, FOXC1 and CARASIL are less frequent. Despite the genetic nature of these disorders, their phenotype, severity and rate of progression may be adversely affected by classical cardiovascular risk factors such as hypertension, diabetes, dyslipidemia and smoking and control of these risk factors is strongly advised for all patients.
 ...
PMID:Hereditary causes of ischemic cerebral small vessel disease. 3087 27