block 7-neurological aging and neuroprotection Flashcards
(43 cards)
watch lecture 1 and maybe lecture 2 if have time but you have flashcards in it on quizlet so probably not
Why study neurological ageing?
helps us understand how to maintain brain health for as long as possible
-since worldwide the population is ageing
what is neurological aging?
-Progressive biochemical, structural and functional changes in the nervous
system that occur over time, leading to gradual declines in motor, sensory,and cognitive functions
structural change- cerebral atrophy
1.Ventricular Enlargement= Brain shrinks → Ventricles expand.
2. Cortical Thinning Cortex (outer brain) becomes thinner.
3. White and Grey Matter Loss : Neurons and their connections are lost.
4.Sulcal Widening=Grooves (sulci) get wider due to tissue loss
-explained in the next card
cerebral atrophy
Cerebral atrophy means that the brain is shrinking or losing tissue.
It happens in many conditions like Alzheimer’s disease, strokes, multiple sclerosis, and normal ageing.
Both the neurons (brain cells) and the connections between them are lost
cerebral atrophy -white matter deterioration
White matter contains fibres that allow communication between brain areas. In cerebral atrophy, white matter deteriorates, leading to slower brain function and disconnection between brain regions.
Types of White Matter Fibres:
Association fibers: Connect different parts of the same hemisphere.
Projection fibers: Connect the brain with the spinal cord and lower brain structures.
Commissural fibers: Connect the left and right hemispheres (e.g., via the corpus callosum).
- each of these fibre connection can be broken down and lead to slow communication
Causes/Problems Associated with White Matter Damage:
small Vessel Disease =Damage to tiny blood vessels, causing poor blood supply to white matter.
Demyelination= Loss of myelin (insulation) around axons, slowing signal transmission.
Microbleeds =Tiny brain hemorrhages that gradually damage white matter.
Leukoaraiosis=Patchy or rarefied white matter seen on brain imaging, linked to aging and vascular disease.
Lacunes (likely typo from “Launes”)=Small cavities formed after minor strokes, damaging nearby white matter.
which mechanisms contributes to the ageing brain
-oxidative stress
-mitochondrial impairment
-impaired proteostasis
-neurological aging]-neuroinflammation
-neurotransmittoer and neurotrophilllic factors decline
what is ros ?
🌟 What are ROS?
Reactive Oxygen Species (ROS) are highly reactive oxygen-containing molecules:
Superoxide (O₂⁻)
Hydroxyl radicals (OH⁻)
Hydrogen peroxide (H₂O₂)
🔥 Sources of ROS
Endogenous (inside the body):
Mitochondrial respiration
Enzymatic reactions (e.g., NADPH oxidases)
Peroxisomal activity
Exogenous (outside factors):
Pollution, tobacco smoke, heavy metals
UV and ionizing radiation
Certain drugs (e.g., Doxorubicin, Paraquat)
-dont have to memorise all
whats the function of ROS?
Help in cell signalling, host defence, and gene regulation.
How ROS Accelerate Brain Aging
Excess ROS damage cells by:
Overwhelming antioxidant systems (SOD, CAT, GSH-Px)
Causing lipid peroxidation (damaging cell membranes)
Causing protein peroxidation (damaging enzymes and structural proteins)
Causing DNA damage (mutations, impaired repair)
Leading to mitochondrial dysfunction
mitochondrial impairment
Genetic mutations in mitochondrial DNA (especially in genes for repair and maintenance) can disrupt oxidative phosphorylation (the main way cells produce energy).
Structural changes in mitochondrial membranes, especially in lipids like cardiolipin, weaken mitochondrial function.
🔥 Key effects of mitochondrial impairment:
Cause Effect
Genetic mutations ➔ Reduced oxidative enzyme activity, weaker electron transport chain (ETC), and shift to glycolysis for energy (less efficient).
Sedentary lifestyle ➔ Increased mitochondrial splitting (fission), excessive mitophagy (mitochondrial removal), more ROS production, and greater genome instability.
Infections ➔ Can trigger mitochondrial stress and damage.
🧠 Final impact:
Less energy production
More oxidative stress (ROS)
Increased cellular aging and dysfunction
What is proteostasis?
Proteostasis = maintenance of healthy proteins inside cells.
Managed by chaperones, the ubiquitin-proteasome system (UPS), and autophagy.
How cells normally handle misfolded proteins:
Chaperones help refold or target misfolded proteins for:
Degradation by proteasomes (small protein shredder inside cells).
Degradation in lysosomes (cellular waste center).
Large protein aggregates are:
Removed by macroautophagy (MA).
Expelled from cells using small vesicles called exosomes.
What happens with impaired proteostasis?
Failure to clear misfolded proteins leads to toxic protein aggregates.
These aggregates spread:
From molecule to molecule.
From cell to cell.
Across brain regions.
🧩 Different protein aggregates cause different diseases:
Example: Different forms of tau and α-synuclein (α-Syn) are linked to different neurodegenerative diseases (like Alzheimer’s and Parkinson’s).
🔥 Impaired Proteostasis and Neuroinflammation:
Misfolded proteins trigger neuroinflammation.
Inflammation then accelerates more protein aggregation and damage, creating a vicious cycle.
🧠 Final effect:
Protein clumps + brain inflammation = worsened brain aging and disease.
neurotransmitter decline with age
Dopamine:
Transporters and receptors decline.
Affects movement, motivation, and reward processing.
Acetylcholine:
Levels fall.
Impacts memory and learning (linked to Alzheimer’s disease).
Serotonin:
Declines with age.
Contributes to mood regulation problems, depression, and anxiety.
GABA:
Levels decline (shown in longitudinal studies).
Leads to less inhibition in the brain → more excitability and anxiety.
Glutamate:
Causes excitotoxicity (too much glutamate activity).
Leads to neuron damage and brain aging.
neurotrophin dceline with age
BDNF (Brain-Derived Neurotrophic Factor):
Supports neuron survival and synaptic plasticity.
Declines with age, leading to weaker brain repair and cognitive decline.
IGF-1 (Insulin-like Growth Factor 1):
Promotes neuron growth and maintenance.
Declines, reducing brain regeneration and cognitive performance.
Other Neurotrophins (NGF, GDNF, VEGF):
Critical for brain health.
Decrease with age, worsening brain degeneration.
decline in cognitive function(mcI stage)
Memory Impairment:
Hippocampal atrophy → Reduced synaptic plasticity (linked to BDNF decline).
Slower Processing Speed and Reaction Time:
White matter degeneration → Slower neural transmission.
Attention and Multitasking Decline:
Prefrontal cortex shrinkage → Reduced working memory (linked to dopamine & acetylcholine decline).
Executive Function Decline:
Frontal lobe activity reduction → Impaired decision-making, problem-solving, planning, judgment, and flexibility.
Short-term Memory Decline:
More affected than long-term memory.
Processing Speed Decline:
White matter degeneration slows neural signal transmission.
Decline in dopamine levels reduces brain network efficiency.
Reduced myelin integrity slows communication between brain regions.
Crystallized Intelligence:
Knowledge and vocabulary remain stable with age.
importance of the MCI stage
Mild Cognitive Impairment (MCI) is a transitional stage between normal age-related cognitive changes and more severe dementia.
MCI often involves memory loss and cognitive slowing that is greater than expected for the person’s age but not severe enough to interfere significantly with daily life.
Early identification of MCI is important for:
Early interventions that may slow progression to dementia.
Monitoring and potentially reducing risk factors for further cognitive decline.
Understanding MCI helps differentiate between normal aging and pathological cognitive decline, providing the opportunity for early therapeutic or lifestyle changes to improve quality of life or delay progression.
assesment of cognitive function
- we use questionaires
-we also now have digital cognitive assessment tool
declines in motor function
Motor Neuron Degeneration:
Leads to reduced force production and dexterity.
Slower Movement & Reduced Coordination:
Loss of dopaminergic neurons → Less efficient motor control (e.g., slower walking, handwriting changes).
Reduced Balance & Increased Fall Risk:
Cerebellar atrophy → Impaired postural control.
Decline in proprioception and vestibular function → Decreased spatial awareness.
Weaker Reflexes & Impaired Reaction Time:
Slower signal transmission in spinal cord and peripheral nerves.
Muscle Weakness & Loss of Fine Motor Skills:
Difficulty with fine motor tasks, contributing to a decline in overall functional abilities.
motor function assessments
- dont need to remember allTimed Up and Go (TUG) Test:
Purpose: Assesses mobility, balance, and fall risk.
Procedure: Measures time to stand, walk 3 meters, turn, and return to seated position.
Use Case: Predicts fall risk in older adults.
One-Leg Stand Test:
Purpose: Evaluates postural control by timing how long one can stand on one leg.
Use Case: Shorter duration indicates fall risk and sensorimotor decline.
Handgrip Strength Test:
Purpose: Measures upper body strength using a dynamometer.
Use Case: Declining grip strength is a predictor of frailty and functional decline.
Finger Tapping Test:
Purpose: Assesses fine motor speed and coordination.
Use Case: Detects neuromuscular decline in aging and Parkinson’s disease.
Heel-to-Toe Walk (Tandem Walking Test):
Purpose: Assesses coordination and cerebellar function.
Use Case: Used to screen for gait abnormalities and neurological deficits.
physical activity definition
Activities involving movement of skeletal muscles that increases in energy expenditure above resting values
