Aging & Neurodegeneration Flashcards
What are some Canadian demographic trends related to aging?
senior population grow by 68% in next 20 years
75+ age group will double
Are younger adults good at forecasting the experiences of older adults?
No
What are 4 physical changes affecting the brain? How do they affect brain?
- Volume loss: overall volume shrinks by 5% per decade after 40, accelerating after 70
- Neurotransmitter depletion: dopamine & serotonin levels decline
- Decreased cerebral blood flow
- accumulation of white matter damage (linked to hypertension/blood pressure)
What is normal & abnormal cognitive & physical changes of aging?
normal: small degree of alzheimer’s pathology (amyloid plaques & neurofibrillary tangles), neuronal loss
abnormal: neuronal loss all around brain, increasing forgetfulness, taking more time to remember/process
What are common socioemotional changes of aging?
- smaller but intentionally chosen social networks (more emotionally close partners)
- greater emotional stability & emotional complexity (+/- tgt) in daily life
What is MCI in terms of memory performance & activities of daily living?
- changes in attention/memory can be noticed by person, friends, family
- cognitive difficulties in excess of normal aging, preserved activities of daily living
What is Dementia (AD) in terms of memory performance & activities of daily living?
- impairment of multiple cognitive functions & activities of daily living
- progressive decline
- syndrome caused by multiple diseases
What are some symptoms of AD?
early symptoms: confusion, irritability, anxiety, deterioration of speech
later symptoms: difficulties w/ simple responses/behaviours (ie. swallowing, speech)
What are predictors of progression to this AD from MCI?
- older age
- APOE e4 status
- Medial temporal lobe atrophy on MRI
- amyloid on PET scan
- Molecular markers in CSF (low AB, elevated total tau & phosphorylated tau)
What is the significance of Apo-E status?
- everyone carries 2 Apo-E genes
- ApoE protein, plays role in cholesterol transport & involved in normal metabolism of amyloid beta
- multiple forms: e2, e3, e4
- if have more copies of e4 = AD frequency higher & mean age younger
What are the 3 defining characteristics of AD?
- Neurofibrillary tangles
- Amyloid plaques
- Volume loss
What is Neurofibrillary Tangles of AD?
- a tauopathy: tau proteins are hyperphosphorylated, misfold & built up
- act as prions: 1 misfold = all misfold
- cell structure compromised
- intracellular
What is Amyloid Plaques of AD?
AB (“beta amyloid”) proteins take on large, collapsed forms & build up in extracellular space
What is Volume Loss of AD?
- progressive loss of both cells & synapses
- appear first in medial temporal lobe structures (entorhinal cortex, amygdala, hippocampus) - involved in memory
What are the 2 theories of AD?
- Amyloid Cascade Hypothesis
- Neurofibrillary (tau) Hypothesis
What is Amyloid Cascade Hypothesis?
dominant AD theory
amyloid plaques are primary symptom & cause all others
evidence: Trisomy 21
problem: high-plaque normals; amyloid drugs keep failing
What is Neurofibrillary (tau) Hypothesis?
holds that misfolded tau is causal agent
evidence: tau pathology correlates w/ cognitive impairment better than AB
problem: tau mutation alone doesn’t seem to cause AB plaques
What are the 3 treatments of AD?
- cholinergic agonists: help prevent decline in learning & memory
- NMDA receptor antagonist: prevent damage to neurons (ie. reduces action of glutamate)
- Target modifiable risk factors: depression, smoking, isolation
**no cures but only attempts too slow down & manage
What are some biomarkers for AD? What is the implication of these results for patients?
- CSF/brain scan/blood test biomarker related to amyloid & tau but not 100% definitive
- inform diagnostic, treatment & referral decisions
- return of biomarker results must be done w/ care
