Cardiovascular System

Question 1

What is the link between cardiovascular health and brain health?

Answer 1

The route for several key areas of brain-body communication is not entirely reliant on nerve cells and pathways

It is also reliant on the vascular system and the blood brain barrier

Cardiovascular system includes all the blood vessels and all those vessels in the brain

Diseased or damaged vasculature impacts on transport of substances - this includes hormones but also nutrients and clearances of waste/toxic substances

Question 2

Is the brain microvasculature part of the cardiovascular system?

Answer 2

Yes

Brain has limited storage capacity - as a highly metabolically active organ, it also requires constant waste clearance

The health of the brain and the maintenance of normal function in brain circuits is thus intimately linked to cardiovascular health

Question 3

What is the neurovascular unit?

Answer 3

Interconnected system of neurons, astrocytes, pericytes and vascular cells (endothelial cells in particular)

Neurovascular unit provides the basis of the blood-brain barrier - underpins neurovascular function and neurovascular coupling

Question 4

What is the link between brain disease and neurovascular function?

Answer 4

There is an increasing recognition of neurovascular disruption in many CNS diseases

What comes first? - Is brain disease causing neurovascular disruption or is it neurovascular disruption causing brain disease?

Question 5

What diseases are linked to neurovascular disruption?

Answer 5

Normal ageing
Brain metastases
Neurotransmitter disturbance
Alzheimers disease
Stroke
Epilepsy
Neuroinflammation

Question 6

Is there a link between cardiovascular health and cognitive function?

Answer 6

There is epidemiological and associative evidence of a link

Kulshreshthra et al (2019) - cardiovascular risk factors and cardiovascular disease positively associated with cognitive decline
i.e., hypertension, smoking, diabetes, obesity

Barnes et al. (2015) - exercise which reduces cardiovascular disease risk is protective of cognitive function

Kandola et al. (2016) - exercise may also enhance cognitive function

Question 7

How does cardiovascular health affect connectivity and function of the brain?

Answer 7

Boots et al. (2019) - Cognitive and connectivity changes associated with CV risk factors in neurologically normal adults

Cardiovascular disease risk is associated with various cognitive functions and this relationship is mediated by connectivity strength in specific brain structures

Question 8

What increases and decreases risk of cognitive decline?

Answer 8

Baumgart et al. (2015)
Increase risk
- TBI (strong evidence)
- Mid life obesity (strong evidence)
- Mid-life hypertension (strong evidence)
- Current smoking (strong evidence)
- Diabetes (strong evidence)
- History of depression (lower evidence)
- Sleep disturbances (lower evidence)

Decrease risk
- Years of formal education (strong evidence)
- Physical activity (strong evidence)
- Mediterranean diet (moderate evidence)
- Cognitive training (moderate evidence)
- Moderate alcohol consumption (lower evidence)
- Social engagement

Question 9

What increases and decreases risk of dementia?

Answer 9

Baumgart et al. (2015)
Increase risk
- TBI (strong evidence)
- Mid-life obesity (moderate evidence)
- Mid-life hypertension (moderate evidence)
- Current smoking (moderate evidence)
- Diabetes (moderate evidence)
- History of depression (unclear evidence)
- Sleep disturbances (unclear evidence)

Decrease risk
- Years of formal education (strong evidence)
- Physical activity (moderate evidence)
- Mediterranean diet (lower evidence)
- Cognitive training (lower evidence)
- Moderate alcohol consumption (unclear evidence)
- Social engagement (unclear evidence)

Question 10

What is the link between physical activity and cognitive function?

Answer 10

Lots of neuroimaging studies showing changes in functional connectivity following exercise interventions

Weng et al. (2017)
30 mins of moderate intensity aerobic cycling selectively increased synchrony among brain regions associated with affect and reward processing learning and memory and in regions important for attention and executive control

Question 11

What is an issue with Weng et al. (2017)?

Answer 11

What if you consider that functional neuroimaging signals themselves are a product of the brain vasculature

It is not easy to tease this apart from the extent to which they provide an index of brain activation and connectivity

Altered vascular reactivity could lead to an apparent reduction in activation when neuronal function remains normal

Question 12

Explain the pathway that vascular factors effect

Answer 12

Complex set of potential pathways

Focused on the neurovascular unit and endothelial cells e.g. endothelial cell dysfunction is a known feature of diabetes, atherosclerosis, hypertension etc

Endothelial cells a core element of macro- and micro- vasculature as well as the blood brain barrier

Question 13

What other factors cause neurovascular breakdown?

Answer 13

Environmental factors = air pollution, low vitamin D

Genetic risk factors = APPSw, APOE4, PSENI

Lifestyle factors = diet, exercise, smoking

Question 14

What cells are the core element of macro-, micro-vasculature and the BBB?

Answer 14

Endothelial cells

Question 15

What conditions have endothelial cells been implemented in?

Answer 15

Endothelial cell dysfunction is a known feature of diabetes, atherosclerosis, hypertension

Question 16

What did Dounavi et al find regarding the role of brain vascular function in diabetes?

Answer 16

Multimodal neuroimaging investigation of brain vascular responses

Comparison of healthy controls, diabetic patients and impaired glucose tolerance patients

Found altered cerebral haemodynamics in impaired glucose tolerance and type 2 diabetes revealed using multi time point aterial spin labelling

Wide range of changes in how blood is delivered to tissue in those with IGT and T2DM

Potential for neuroimaging biomarkers of neurological risks in diabetes

Question 17

What are the effects of glucose on neurovascular function in zebrafish?

Answer 17

Chhabria et al (2018)
Development of a zebrafish model to study the impact of altered neurovascular function on brain function and cognition

Huge potential to explore gene interactions and molecular signalling pathways using zebrafish

Transparent when young so can image them easily
Showed impacts on brain blood vessel development as well as vascular responses to sensory stimuli

High blood glucose impaired neurovascular function

Question 18

What brain systems control cardiovascular function?

Answer 18

Cortical - cortex
Subcortical - thalamus, amygdala, hippocampus
mid brain, hypothalamus (hormone release)
Brainstem - pons/medulla
control sympathetic activity, respiratory activity (autonomic nervous system)
Motor activity (freezing)

Question 19

How is stress related to cardiovascular function/disease?

Answer 19

Brain circuits controlling cardiovascular function do so via activation of the autonomic nervous system

These circuits receive input from cortical and subcortical systems and are responsive to a wide range of physiological and psychological stimuli

This links back to stress

The continued presence of stressors can increase the presence of cardiovascular risk factors and lead to cardiovascular disease

Question 20

What are the mechanisms of stress on cardiovascular function?

Answer 20

Stress causes a physiological response which acts on the HPA axis, the sympathetic nervous system, stress-responsive humoral factors

The sympathetic nervous system causes increased oxygen consumption, increased blood pressure, increased heart rate, links to thrombosis and coagulation which can cause cardiovascular disease

The HPA axis causes changes in glucose metabolism - impaired glucose tolerance, insulin resistance
Changes to lipid metabolism
Links to obesity
All risk factors for cardiovascular disease

Question 21

What are the feedback loops between the brain and cardiovascular system?

Answer 21

Brain circuits for cognition and affect link to hormone and endocrine systems and the autonomic nervous system
Autonomic nervous system and endocrine system link to the cardiovascular system
cardiovascular system links to brain health which links back to brain circuits for cognition and affect

Question 22

What are the mechanisms of cardiovascular system feedback to brain systems?

Answer 22

Stress related modulation of cardiovascular and metabolic function can feedback to the brain e.g., cortisol related amygdala or hippocampal activation

Also, visceral (internal organs) sensation and interoceptive input - the brain receives ongoing input regarding body state via visceral sensory afferents and via sensing of blood-borne chemical - this underpins interoceptive input to brain systems at multiple levels

Inflammation and sickness behaviour

Brain-gut interactions

Question 23

What is interoception?

Answer 23

Interoception means sensing internal signals from your body, like when you are hungry, when your heart is beating fast, or when you need the toilet

Question 24

How do brain-gut interactions affect brain function?

Answer 24

Morera et al. (2019)

The mechanisms underlying microbiota-gut-brain axis communication involves neuro-immune-endocrine mediators

This interconnected network includes the central nervous system (CNS), the autonomic nervous system, the enteric nervous system and the HPA

Changes in gut microbiome composition has been already related to cognitive disorders and mental illness

Question 25

How does exercise effect brain health?

Answer 25

Stimpson et al. (2018)

Physical activity increases cardiovascular fitness, improving cerebral circulation (eNOS increases, CBV increases)

This leads to the upregulation of neurotrophins and supporting factors increasing brain plasticity

Brain plasticity induces structural changes and functional enhancement of new neurons giving cognitive benefits

Question 26

How does exercise act as a stress buffer?

Answer 26

Zschuke et al. (2015)

Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health

Participants with a higher aerobic fitness showed lower cortisol responses to the MIST (stress task)

Acute aerobic exercise reduces the neural and cortisol stress response to the MIST

The magnitude of mood and endocrine changes observed correlated with brain activation magnitude

Acute stress-buffering effect of exercise relies on negative feedback mechanisms