Case 3 - vascular dementia

Question 1

capillary types

Answer 1

continuous
fenestrated
open pore

Question 2

neurocapillaries

Answer 2

• Continuous  in the brain where they associate with microglia and astrocyte endfeet
• Endothelial cell
• Pericyte
   Control angiogenesis
   Stem-cell properties
   Inflammatory responses
   Regulation of flow
   Regulation of BBB
• Continuous basement membrane

Question 3

neurovascular coupling

Answer 3

• Neurovascular coupling refers to the mechanism that links the transient neural activity to the subsequent change in cerebral blood flow, which is regulated by both chemical signals and mechanical effects
• Neurons  neurotransmitter  astrocyte  hormones  capillary  effect (dilation/constriction)

Question 4

epidemiology

Answer 4

• Vascular dementia, a heterogeneous group of brain disorders in which cognitive impairment is attributable to cerebrovascular pathologies, is responsible for at least 20% of cases of dementia, being second only to Alzheimer’s disease
• The prevalence of VaD increases linearly with age

Question 5

pathophysiology

Answer 5

• By far, the most prevalent vascular lesions associated with VCI are related to alterations in small vessels in the hemispheric white matter
• These microvascular alterations result in different neuropathological lesions
• Vascular dementia is the advanced stage of vascular cognitive impairment which can be associated with several neuropathologies

Question 6

Cerebral small vessel disease - pathogenesis

Answer 6

• Pathogenesis is thought to begin with a specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit
• Can be a stroke or infarct
• Can be mutation
• Can be head trauma

Question 7

CSVD - pathophysiology

Answer 7

• Diffuse damage to the white matter (ischemic leukoencephalopathy) is the most common pathology in SVD
• The mechanism underlying white matter lesions (WMLs), which lead to demyelination and gliosis, involves a multifactorial process, including BBB disruption, hypoxia and hypoperfusion, oxidative stress, neuroinflammation and alteration on NVU coupling

Question 8

risk factors

Answer 8

• Age
• Female sex
• Hypertension –> can lead to infarcts and strokes which can contribute the pathogenesis of CSVD
• Diabetes –> Diabetes mellitus is characterised by both microvascular and macrovascular pathology due to tissue exposure to chronic hyperglycaemia (can cause ROS and advanced glycation end-products)

Question 9

genetics

Answer 9

• Vascular disorders are sporadic by nature, though a familial component has been observed
• AD and VaD share several features and both are generally considered complex and heterogeneous
• APP
• PSEN-1 and 2
• Apo4e
• Sporadic cerebrovascular disease genes: genes that are associated with stroke risk can be at the heart of vascular dementia
• Example: Apo-E –> also links to AD
• Familial stroke genes

Question 10

biomarkers

Answer 10

• Neuroimaging –> MRI to detect white matter lesions
• Blood biomarkers:
• CRP level –> high CRP was independently associated with VaD, but not AD.
• CSF biomarkers:
• Albumin level –> reflects BBB disruption so predicts VaD

Question 11

prevention/treatment

Answer 11

• Prevention aims to reduce the disease by eliminating its cause or main risk factors, particularly:
• Hypertension –> antihypertensive agents (diuretic or beta-blockers)
• Diabetes mellitus –> control glycemia