PSYC 301: Aging & Neurodegeneration

what is normal cognitive aging?

• differential impacts on some cognitive domains over others

  • LTM & WM decline but vocab stays relatively stable

• processing speed declines

• individual variation

what are 4 normal brain changes in aging?

1) volume loss

2) neurotransmitter depletion

3) decreased blood flow

4) white matter damage

what is normal socioemotional changes of aging?

• smaller but better quality social networks w/ higher proportion of emotionally close partners

• greater emotional stability & emotional complexity in daily life

what are considered normal brain changes of aging?

small degree of alzheimer’s pathology & neuronal loss

what are abnormal brain changes of aging?

• increasing forgetfulness

• language, attention, exec function, problem solving, & visuospatial intact

• drive without difficulty

• taking more time to remember

• behaviour & mood stable

what are characteristics of MCI?

• changes in attention & memory that is noticeable to the person, friends, & family

• cognitive difficulties in excess of normal aging; preserved activities of daily living

what is dementia?

impairment of multiple cognitive functions & activities of daily living

what causes dementia & does it typically onset?

• syndrome caused by multiple diseases

• middle-to-late adulthood

what are early symptoms of alzheimer’s disease?

• confusion

• irritability

• anxiety

• deterioration of speech

what are later symptoms of AD?

difficulties w/ even simple responses or behaviours (swallowing, speech)

what predicts the progression from MCI to AD?

• older age

• APOE E4 status

• MTL atrophy on MRI

• positive amyloid on PET scan

• molecular markers in CSF (low AB, elevated total tau & phosphorylated tau)

what is the clinical significance of apo-e status?

• everyone has 2 Apo-E genes

• protein that plays a role in cholesterol transport & involved in normal metabolism of amyloid beta

• 3 forms: E2, E3, E4

what are 3 characteristics of AD?

1) neurofibrillary tangles

2) amyloid plaques

3) volume loss

what are neurofibrillary tangles?

• tauopathy

• act as prions

• cell structure is compromised

  • intracellular

what is tauopathy?

tau proteins are hyperphosphorylated, misfold, & build up

what are amyloid plaques?

proteins take on large, collapsed forms & build up in the extracellular space

what is volume loss?

progressive loss of both cells & synapses, appearing 1st in MTL structures involved in memory

what 3 MTL structures does volume loss occur in?

• entorhinal cortex

• amygdala

• hippocampus

what are structural changes that occur in the progression of AD?

• disease spreads thru brain, causing progressive loss of connections between neurons, & then neurons themselves

• later stages, the brain shrinks & the cerebral cortex appears shrivelled & the fluid-filled venticles are expanded

what are microscopic changes that occur in the progression of AD?

• accumulations of amyloid plaques form between neurons

• microtubules associated w/ tau protein accumulates in neurofibrillary tangles & they persist after neurons have died

what are the 3 theories of AD?

1) neurofibrillary (tau) hypothesis

2) amyloid cascade hypothesis (dom)

3) lithium deficiency theory

what is the neurofibrillary hypothesis?

holds that misfolded tau is the causal agent

what is the evidence for this theory?

tau pathology correlates w/ cognitive impairment better than AB

what is the problem w/ this theory?

tau mutation alone does not seem to cause AB plaques

what is the amyloid cascade hypothesis?

holds that amyloid plaques are the primary symptom & cause all others

what is the evidence for this theory?

trisomy 21

what are the problems w/ this theory?

• high-plaque normals

• amyloid drugs keep failing

what is the lithium deficiency theory?

holds that amyloid plaques bind endogenous lithium, reducing its normal function in the brain, & that lithium depletion activates microglia, impairing their ability to degrade amyloid

what is the evidence for this theory?

mice models have used supplementing w/ a form of lithium that avoids binding amyloid, preventing pathological changes & memory loss

what is the problem w/ this theory?

no human studies

what are 3 treatments for AD?

1) cholingeric agonists

2) NDMA receptor antagonist

3) target modifiable risk factors

what can cholingeric agonists help w/?

can help prevent decline in learning & memory

what can NDMA receptor antagonists help w/?

can prevent damage to neurons

what are modifiable risk factors?

• depression

• smoking

• social isolation

what is a biomarker for AD?

CSF biomarkers for AD are related to amyloid & tau are helpful but not 100% definitive

what do the biomarkers for AD mean for patients?

• can inform diagnostic, treatment, & referral decisions

• return of biomarker results must be done w/ care

  • “wasn’t all in my head” => relief

  • "make meaning out of struggles”