Alzheimers disease patho

AD presentation

memory loss, behavioral changes, functional decline

Amyloid plaque formation 1

Accumulation of amyloid-beta peptides

Amyloid precursor protein is cleaved, forming a sticky aggregate

Amyloid plaque formation 2

Amyloid-beta induces neuroinflammation -->

Injury/neuronal death

Tau pathology

Tau hyperphosphorylation

Tau misfolding and aggregating into tangles

Tangles induce neuronal death

NTM deficits in AD

Decrease: ACh, serotonin, NE, DA

Increase: glutamate

Decreased ACh in AD

memory impairment

poor attention

Increased glutamate in AD

excitotixicity

Neuronal death

Decreased serotonin in AD

Depression, anxiety, sleep issues

Decreased NE in AD

inattention, agitation, anxiety

Decreased DA in AD

reduced motivation, executive dysfunction, apathy

AD DSM-5 criteria

Memory +1 other impairment

decline interfering w/ independence

gradual onset, progressive worsening

Stroke, delirium, major psychiatric illness

Early AD px

episodic memory loss, subtle language problems

Middle AD px

impairment of orientation, visuospatial skills, executive function, personality changes

Late AD px

severe cognitive decline, dependence of daily living

Normal mini-mental state exam value

>24/30

AD non-pharm tx

CBT, lifestyle and risk modification

ChEI's drugs for AD

Donepezil, rivastigmine, galantamine

Donepezil

Reversible AChE inhibitor

ADE: GI upset, bradycardia, insomnia

Rivastigmine

Pseudo-irreversible AChE/ BChE inhib

ADE: GI upset (oral), skin irritation (patch)

Galantamine

Reversible AChE inhibitor, enhances nicotinic r activity

ADE: GI upset, wt loss, SJS

NMDA r agonist drug

memantine

memantine MoA and indication

NMDA r antagonist that blocks Ca2+ influx

Used in moderate to severe AD

Memantine ADE

CNS, GI, Cardio (HTN, somnolence, fatigue)

Memantine monitoring

renal impairment

ADEs for all ChEIs

dizziness, syncope, insomnia

DUMBBELLS

Anti-amyloid drugs

Aducanumab, lecanemab, donanemab

Anti-amyloid concerns

amyloid related imaging abnormalities (ARIA)

Edema, hemorrhage, cost

Anti-tau therapies

aggregation inhibitors

Tau immunotherapies