NSCI 302: Memory, amnesia and AD

The case of s.

• A.R. Luria studied S. for over 30 years

• S. has extraordinary memory (eidetic memory) and synaesthesia (seeing numbers as ppl, or colors when hearing sounds)

• was able to recite the contents of the table in any direction

• used the method of loci: uses space and place to remember info

The case of M.B

• had manic-depressive psychosis

• also had bilateral medial temporal lesion like H.M.

• recent memory was normal, but was later impaired

• she could not describe any other part of the hospital although she had been living there continuously for nearly three and a half years

• she was stuporous and confused for one week

• recovered rapidly and without neurological deficit

• verbal intelligence proved to be normal

Korsakoff’s syndrome

• thiamine (vitamin B1) deficiency

• no thiamine for 2-3 weeks = cannot form long term memories

Korsakoff’s syndrome effects

• severe anterograde and retrograde amnesia

• sensory and motor problems

• extreme confusion

• personality changes

amnesic syndrome

• medial diencephalic amnesia

• thiamine-deficiency → damage certain nuclei in the medial diencephalon

medial diencephalon nuclei

• anterior thalamic nuclei

• mammillary bodies

• mediodorsal thalamic nuclei

dementia history

• was once a generic term for any form of mental illness

• meaning: to be outside of one’s own mind

• initially identified as the terminal phase of any form of mental illness

senile dementia

• jean-etienne esquirol

• related to old age

• alterations in memory (recent)

• difficulties with attention

emil kraeplin

distinguished between early and late form of dementia

etienne-jean georget

raised the concept of irreversibility of dementia

common dementias

• AD

• vascular dementia

• dementia with lewy bodies

• fronto-temporal dementia

• PDD

vascular dementia

due to small infarcts (ischemic damage)

early history of AD

• Alois Alzheimer presents a case of pre-senile dementia

• patient name: Auguste Deter

• Alzheimer conducts a post-mortem analysis of Deter’s brain

• He reported the presence of senile plaques and neurofibrillary tangles

later history of AD

• AD diagnoses was reserved for pre-senile forms only

• major changes in AD research with EM

DSM-I (1952)

no mention of dementias

DSM-II (1968)

AD classified as pre-senile dementia

DSM-III-R (1987)

pre-senile and senile forms of AD appear

DSM-5 (2013)

“dementia” replaced with “major neurocognitive disorder”

AD sex diff

• 2x more likely in females

• due to hormones and lifestyle

AD definition

progressive disorder that results in dementia and death

AD early symptoms

selective declines in memory

AD later symptoms

confusion, irritability, anxiety, and deterioration of speech

AD advanced stages

difficulties with even simple responses e.g. swallowing and bladder control

EOAD

• diagnosis before 65

• 5-10% of all AD cases

LOAD

• diagnoses after 65

• 90-95% of AD cases

mild cognitive impairment (MCI)

cognitive symptoms that precede AD diagnosis

first signs (MCI)

• short term memory loss

• prospective memory issues

prospective memory

memory for the things u plan to do

early signs of AD

• memory for new facts/episodes selectively affected

• memory for older episodes, semantic memory and implicit memory not rlly affected

medium

long term episodic memory begins to be affected

tau

• important for stabilizing MTs

• cell collapses w/o = cell death

3 defining characteristics of AD

1. Tau tangles

2. amyloid plaques

3. substantial decrease in brain volume

substantial decrease in brain volume

due to:

• loss and shrinkage of neuronal processes (synapse loss)

• loss of neurons

tau tangles

• intracellular markers

• dominantly present in temporal lobe

amyoid plaques

• first show up in temporal → posterior parts

• already at a max when MCI happens

first area of the brain to be affected by AD

hippocampus = severe tissue loss and important for memory formation

AD biomarkers

1. low amyloid-beta levels in CSF: forms plaques in cortex so cannot diffuse into CSF

2. high tau levels in CSF

3. decrease in hippocampal volume (MRI)

4. decrease in brain metabolism (FDG-PET)

5. Amyvid and PET

6. suggestions of a potential blood test for amyloid-beta

decrease in brain metabolism (FDG-PET)

diaschisis one form of this but not related to AD

Amyvid

• sticky, radioactive dye

• sticks to amyloid beta plaques

theories of AD pathogenesis

1. Amyloid cascade hypothesis

2. Tau hypothesis

3. inflammation hypothesis (microglia)

Amyloid cascade hypothesis

• lots of criticism

• “high plaque normals” - no cognitive symptoms but have high plaque around amyloid beta protein = no inflammation

prions

proteins that cause other proteins to misfold

inflammation hypothesis (microglia)

microglia try to remove plaques but then become maladaptive = leads to system going awry

AD risk factors

• alcohol abuse

• diabetes

• air pollution

• vitamin D deficiency

• depression

AD current treatments

• acetylcholinesterase inhibitors

• NMDA-receptor antagonists

• aducanumab to remove amyloid plaques

• SSRIs for symptoms of depression in AD (lil evidence)

• atypical antipsychotics for psychotic symptoms and agitation (calms anxiety)

acetylcholinesterase inhibitors

• many ppl with AD have long Ach

• so raises Ach levels in the brain

• e.g. donepezil (not so bad side effects)

• older ones have nasty side effects

• help mostly for EOAD

• improve cognition

NMDA-receptor antagonists

• memantine for moderate to severe AD

• limit neurotoxicity

• improve cognition

aducanumab

• very controversial

• amyloid-beta directed antibody

• vv expensive