Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

B364 > L9, Brain Aging > Flashcards

L9, Brain Aging Flashcards

1
Q

What broad anatomical changes take place in the ageing brain?

A
  • Loss of brain weight
  • Shrinkage of grey matter
  • Loss of cells
  • Loss of synapses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Demographic changes in dementia:

Prevalence and incidence, sex differences

A
  • Increased prevalence in older people general
  • 20 fold increase in incidence from 65 to 89 (across various studies)
  • 16% incidence above 90 yrs
  • These proportions have been decreasing despite an increase in total cases
  • Affects sexes in similar proportions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Types of dementia in women vs men:

A
  • Alzheimer’s (AD), the most prevalent ND overall, is more frequent in women
  • Parkinson’s (PD) is more frequent in men
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Issues around natural ageing and dementia studies:

Bias, risk factors, model organisms

A
  • Age is a major risk factor for neurodegenerative diseases
  • NDs must be excluded in ‘natural brain ageing’ in humans is to be studied
  • Pre-clinical forms of these diseases may also need to be excluded but they are hard to detect
  • Collection bias, participation bias
  • Domestic pets (dogs) can be useful model organisms in aging studies (similar mechanisms and environment to humans)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Primary impairments and pathology of AD

A
  • Memory and language
  • Plaques and tangles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Primary impairments and pathology of Vascular Dementia:

A
  • Poor concentration, physical symptoms (limb paralysis/weakness)
  • Hypertension and mini-strokes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Primary impairments and pathology of DLB:

A
  • Hallucinations, fluctuating memory impairment
  • Lewy bodies throughout cortex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Primary impairments and pathology of Parkinson’s dementia:

A
  • PD with dementia (movement disorder)
  • Lewy bodies, neural degeneration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Primary impairments and pathology of frontal lobe dementia:

A
  • Personality and behavioural changes
  • Frontal lobe degeneration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Primary impairments and pathology of alcohol-related dementia:

A
  • Memory, planning, social skills, judgement, balance
  • Excessive alcohol intake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Is natural brain ageing a major cause of dementia? - Arguments in favour

A
  • <3% of dementia cases cannot be attributed to a particular type fo the disease
  • Key features of well-known NDs can be seen in ‘naturally aging’ brains
  • e.g. Protein aggregates and tangles are observed in old brains (as in AD)
  • e.g.Dopaminergic synapses are lost with age (as in PD)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

ND pathologies by region:

AD, PD, ALS

A
  • AD: Hippocampal ageing
  • PD: Substantia Nigra ageing
  • ALS: Spinal chord ageing

Most NDs are diagnosed based on symptoms revealing region-specific impairments
…But natural ageing combined with regional susceptibility may underly NDs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Discussion: Age related changes at regional, cellular and molecular level

A
  • Regional: Loss of grey or white matter in different regions
  • Cellular: Astrocytes, neurons, microglia
  • Molecular: Iron accumulation, synaptic perturbation, impaired protein degradation, altered translation, Mitochondrial dysfunction, calcium dysregulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mature Adult brain features

A

Adult brain cortex:
* 1.2 to 1.34 kg
* 1x10^11 neurones
* 2.5x10^15 synaptic connections
* 1:1 glia to neuron ratio
…Neurones live as long as we do and glial cells are just as abundant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Organ and tissue level changes to brain with age

A
  • Brain grows 25% in volume between 2 and 15 yrs
  • Brain weight and volume decrease with age
  • This is mostly due to a loss in grey matter -> contains most of cell bodies whereas white matter contains mostly axons
  • Between 16-80 yrs, brain shrinks to the size of 2-3 yrs
  • Cerebrospinal fluid (CSF) volume increases with age
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Gray matter and white matter makeup

A
  • Gray: Dendrites, axon terminal of presynaptic cell, cell body
  • White: Myelinated cells and oligodendrocytes (making myelin)
17
Q

Frontal lobe studies in brain ageing

A
  • Cross-sectional MRI in 148 healthy volunteers (in vivo)
  • Prefrontal gray matter declined most with age
  • Volume of temporal and parietal cortices, and hippocampus decreases too, but less so
  • Sensory and motor region, including occipital cortex. tend to be preserved
    -> definitely regional changes
  • Frontal lobes mature last but are amongst first to decline
18
Q

Orbitofrontal/Pre-frontal cortex ageing:

A
  • The prefrontal cortex updates and stores information about outcomes that will follow choices
  • It thus impacts learning and memory, emotion control/social behaviours and decision-making processes
  • The PFC is most affected by age
  • It is a key subregion, strongly affected in AD
19
Q

Episodic memory: Changes in AD vs normal ageing

A
  • There are changes in cognition in the ‘disease-free’ elderly population, but this is not inevitable
  • Memory impairment occurs across all species (e.g. rats, monkeys, humans) some of which do not develop AD
  • Ability to encode new memories of events or facts show decline in both cross-sectional and longitudinal studies
  • Episodic memory is especially impaired in normal ageing (recall of personal experiences at particular time and place)
20
Q

Neuronal cell loss hypothesis for grey matter loss:

A
  • Grey matter mostly made-up of neuron cell bodies -> grey matter loss due to cell loss
  • Various studies -> cell loss is minimal during brain ageing
21
Q

Dendrite and synapse loss hypothesis for grey matter loss:

A
  • Grey matter hosts most synapses, with cortical brain layers characterised by high dendritic density
  • Performant cognition enabled by synaptic network rather than absolute cell numbers
  • Age-related decline in cognition is more likely to be due to loss of dendrites and synapses
  • Many studies have shown this including studies into aged rats -> loss of pyramidal neurons with age, shrinkage of cell body, loss of basal dendritic branches (NOT apical)
22
Q

Aberrant dendritic growth in man, mice and worms…

A
  • In man, hippocampal neurones grow more dendrites in mid to old age, although they seem to lose dendrites after 90
  • In mice, retina rod bipolar cells also increase their dendritic length with age in mouse models
  • In worms, ageing neurons sprout new dendrites but synapses dynamics are not compromised
    -> Supports hyperfunction theory of ageing
23
Q

Plasticity vs synapse stability

A
  • The aged brain largely retains plasticity but synapses lose stability
  • Density of ‘en passant’ boutons are similar
  • But EPBs more dynamic/less stable and shorter-lived
  • Less presynaptic contacts or vesicles may explain lesser synaptic stability/strength with age
24
Q

Measuring synaptic strength

A
  • Long term potentiation: Basis of long term memory; synapse repeatedly stimulated -> more dendritic receptors -> more transmitter molecules -> stronger link at the synapse
  • Memory is stored in the brain through changes in the strength of synaptic connections
  • Results in larger electrical response in post-synaptic cell -> Measure of synaptic strength
25
Q

LTP decrease in age:

Studies in rats

A
  • LTP decay is faster in older rats (strength lost quicker)
    -> Results in lesser synaptic stability
    -> Reflected in poorer spatial memory performance
    –> Ageing neurons: Not much cell loss, similar branch dynamics and complexity, shrunk cell bodies, less stable synapses, LTP decay
26
Q

Neurone key qualities in relation to ageing effects: (2 advantages and one disadvantage)

A
  • Neurones are highly-specialised and long-lived; don’t divide so telomere dysfunction does not affect them
  • They are naturally good at clearing protein damage since they strongly rely on efficient proteostasis and endolysosomal functions (autophagy, exophers)
  • However, they do not do well in energy depletion/ starvation/ metabolic shifts
    -> require effective energy supply
    -> rely critically on other brain cells and the brain milieu
27
Q

How do myeloid cells become energy depleted with age?

Effects of energy depletion:

A
  • Myeloid cells become energy-depleted with age (PGE2-EP2 signalling)
  • Cells can use various substrates as fuel; however myeloid cells in aged mice lose the capacity to use fuels other than glucose
    -> PGE2 signalling increases with age -> PGE2 signalling on EPR2 lowers available glucose
    -> Myeloid cells starve and become pro-inflammatory -> increased cytokine secretion by brain and plasma myeloid cells in vivo
    -> Leads to cognitive decay
28
Q

Key systemic factors involved in age-associated brain dysfunction (inflammation of brain):

A

Increased…

  • TNF
  • IL-1beta
  • CCL2
  • Type 1 interferon

Decreased…

  • IL-4
  • Type II interferon
  • IL10
    -> All these may contribute to brain inflamm-ageing
29
Q

Cellular and subcellular hallmarks of brain ageing

A
  • Mitochondrial dysfunction
  • Impaired molecular waste disposal
  • Impaired DNA repair
  • Aberrant neuronal network activity
  • Stem cell exhaustion
  • Glial cell activation and inflammation
  • Impaired adaptive stress response signalling
  • Dysregulated neuronal calcium homeostasis
  • Oxidative damage
    …All interlinked; largely due to systemic issues, possibly also hyperfunction issue
30
Q

Is natural brain ageing unavoidable?

Differences between individuals, blood rejuvenation

A
  • Heterogeneity; Some individuals can utilise certain compensatory mechanisms (eg. centenarians)
  • Examples of counteracting age-related cognitive decline by plastic reorganisation of existing neural pathways (i.e. bilateral results in high performing aged individuals vs right lateral otherwise)
  • Milieu shown to reverse brain ageing
31
Q

Pharmacological Interventions into metabolism

A
  • Keto diet: Improves kidney and brain function but difficult to achieve ,kidney stone and muscle loss issues
  • Rapamycin: Pleiotropic effects; recently failed clinical trials
  • Metformin: beneficial effects in cancer, diabetes, processed by microbiota (clinical trials ongoing)
  • Senolytics; removing senescent cells?
32
Q

Gut microbiota

A
  • Healthy gut improve brain ageing (Restoring a youthful gut microbiota)
  • Shifts in gut microbiota robustly linked to NDs and neuropsychiatric disorders
  • Linked to inflamm-ageing
33
Q

Lifestyle interventions for brain aging

A
  • Exercise Improves brain ageing
    -> Considerable evidence in athletes as well as general population
    -> Strongly linked with nutrition (especially protein intake in older age)
  • Diet (more protein)
  • Good Sleep (8 hrs)

B364 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions