Introduction Flashcards
(37 cards)
What is the prevalence of cSVD?
- age related vasculopathy
- leading cause of vascular cognitive impairment
- 1/5th all strokes
- 1/4 all ischaemic strokes
- 6-10x prevalence of large vessel stroke
-widely varies due to lack of standardised definition & diagnostic criteria for cSVD
What are the functions of cerebral arterioles?
- perfusion of brain tissue
- removal of waste
- BBB excludes toxic chemicals
- neuroimmune functions
- local changes in blood flow (crucial to funcitoning)
What are the components of the neurovascular unit?
- neurons
- astrocytes
- endothelial cells
- myocytes
- pericytes
How does endothelial-derived NO cause relaxation & increased vessel diameter?
NO activates guanylyl cyclase (GC), GTP to cGMP, PKG & muscle relaxation
Beyond basic functionality there is still much unknown about cerebral arterioles…
In both health & disease
Sequaelae of cSVD
- vascular cognitive impairment & dementia
- diffuse white matter lesions
- lacunar stroke
- microhaemorrhages
- urinary incontienence
- gait distrubance
Types of cSVD
- arteriolosclerosis (most common, me)
- lipohyalinosis (foam cells as well as fibrohyaline)
- hereditary e.g. CADASIL
-cerebral amyloid angiopathy (simiarl condition, Abeta in vessel walls)
Treatment of cSVD
- only symptomatic (no disease modifying drugs)
- treat risk factors e.g. cholesterol, HTN
- anti-platelet treatment of lacunar ischaemic stroke
-target BBB or NVU?
Pathophysiology of cSVD (Lammie, 2002)
- fibro-hyaline thickening of the penetrating arteries
- depletion of vascular smooth muscle cells
- enlongated & tortuous vessels
- narrowed lumina, thickened walls
- enlarged perivascular spaces (formed from pia as arteries dive deep into brain)
- pallor of staining/loss of myelin
- loosening of parenchymal tissue
What happens to autoregulation?
- COMPROMISED leaving brain without adaptive changes to shifts in local metabolic demands
- brain vulnerable from low pressure (can’t dilate)
- as well as high pressure (associated with damage) states
What happens to cerebral blood flow in cSVD?
-Low
Other possible contributors to pathogenesis of cSVD? (Pantoni, 2010)
- acute vessel occlusion
- vasospasm
- BBB incompetency (mixed evidence)
- local subclinical inflammaiton
- oligodendeocyte apoptosis
-NO/cGMP pathway?
Methods of investigating cSVD?
- histopatholgical studies
- MRI (lacks resolution to visualise vessels in vivo)
- spontaneously hypertensive stroke prone rat (Bailey et al)
- clinical risk factor studies
Risk factors for cSVD
- age (WHY I’M LOOKING AT OLDEST OLD)
- family hx
- HTN
- smoking
- DM
- inactivity
- obesity
- hypercholesterolaemia
-not sex as with cardiovascular, stroke risk equal in men and women
The single largest identifiable risk factor for dementia apart from age is…
-VASCULAR PATHOLOGY
The fastest growing population subroup is persons…
> 85yrs (Nelson et al., 2011)
The major determinants of morbiidty & mortality in persons >90yrs are…
-disability & depression (replacing smoking, obesity & socioeconomic factors)
Persons >90yrs are less prone to…
-OXIDATIVE STRESS
The oldest old are defined as….
- Either persons over 85 or 90yrs
- I appreictae the interestingness of this subgroup but due to cohort size am looking at 80yr year olds what I am calling “older people”!
Imhof et al., 2007 obesered that mean diameter of the hippocampal microvasculature in individuals >90yrs is an important determinant in…
-COGNITION
What are resilience factors?
-Quirks which provide protection against pathology in the elderly, perhaps allowing compensatory processes to develop
Name 4 hypothesised resilience factors:
1) APOE2 (chr19) for AD (thought to bind & influence clearance of APP)
2) Increased VEGF conc for AD (more optimal brain ageing, especially in AD pts)
3) Increased blood vessel density (could prevent decreased CBF associated with cognitive decline)
4) *Delayed vascular smooth muscle senescence may protect against cSVD - MY HYPOTHESIS!
Define senescence
- permament exit from the cell cycle
- DNA resembles G1
- ageing at a cellular level
Name two types of senescence
- stress induced premature senescence
- replicative senescence
