8. NSS alzheimers

Alzheimer's disease (AD)

A progressive, degenerative disorder that attacks the brain's nerve cells (neurons), resulting in loss of memory, thinking and language skills, and behavioral changes. No cause is known, and no cure has been found.

Who Alzheimer's disease is named after

Dr. Alois Alzheimer, who in 1906 noticed changes in the brain tissue of a woman who had died of an unusual mental illness.

AD pathological result

Results from the destruction of cholinergic and other neurons in the cortex and limbic structures of the brain.

AD prevalence in dementia

Accounts for about 60% of all cases of dementia in patients over 65 years of age.

AD mortality

Associated with more than 100,000 deaths each year.

AD prevalence by age

An estimated 10% of individuals over age 65 and nearly half of those age 85 or older have Alzheimer disease.

Role of acetylcholine in AD

Acetylcholine is an important neurotransmitter in brain regions involved in memory; loss of acetylcholine in AD correlates with impairment of memory.

Role of glutamate in AD

Overstimulation of glutamate receptors, particularly of the NMDA type, may result in excitotoxic effects on neurons and is suggested as a mechanism for neurodegenerative or apoptotic (programmed cell death) processes.

Current therapies aim (1)

Improve cholinergic transmission within the brain.

Current therapies aim (2)

Prevent excitotoxic actions resulting from overstimulation of NMDA-glutamate receptors.

Central acetylcholinesterase inhibitors

Tacrine, Donepezil, Rivastigmine, Galantamine.

Tacrine

Has lower bioavailability and a shorter half-life compared to other AChE inhibitors.

Donepezil pharmacokinetics

Well absorbed after oral administration; long half-life of about 70 hours; administered once daily.

Donepezil side effects

Diarrhea, nausea, vomiting, salivation, miosis; usually mild and transient.

Advantage of donepezil over tacrine

Unlike tacrine, donepezil is not associated with hepatotoxicity.

Rivastigmine formulation

Used as a transdermal patch.

Galantamine mechanism (1)

Competitive inhibition of acetylcholinesterase.

Galantamine mechanism (2)

Allosteric modulation of presynaptic and postsynaptic nicotinic receptors.

Memantine mechanism

Acts by blocking the NMDA receptor and limiting Ca2+ influx into the neuron.

Memantine administration

Administered orally; given twice-daily or as a sustained release capsule; excreted largely unchanged in urine.

Memantine side effects

May cause confusion, agitation, and restlessness.

Memantine combination therapy

Often given in combination with an AChE inhibitor.

Lecanemab

A monoclonal antibody medication; an amyloid beta-directed antibody.

Lecanemab approval

Granted accelerated approval in the United States in January 2023; fully approved by the FDA in July 2023.

Lecanemab mechanism

Works by targeting and removing Amyloid beta (Aβ) from the brain.

Role of amyloid beta in AD

Forms clumps and plaques in the brain, which are thought to contribute to the decline in cognitive function seen in Alzheimer's disease.

Lecanemab (Leqembi) administration

Given via intravenous infusion.

Lecanemab adverse effects

Back pain, blurred or changes in vision, chest tightness, chills, confusion, diarrhea.

Caprylidene

A medical food that is metabolized into ketone bodies, which the brain can use for energy when the processing of glucose is impaired.