Dementia

Dementia is a term that describes a group of symptoms affecting memory, thinking and social abilities. Dementia isn't a specific disease; several diseases can cause dementia. Dementia is amongst the leading causes of death and disability in the global elderly population.

Vascular dementia is caused by damage to blood vessels in the brain. Blood vessel problems can cause strokes or damage white matter fibers in the brain.

Lewy body dementia is associated with deposits of balloon-like clumps of proteins (i.e, Lewy bodies) in the brains of people with Lewy body dementia, Alzheimer's disease and Parkinson's disease. This is one of the more common types of progressive dementia. Common signs and symptoms include acting out dreams during sleep, visual hallucinations, and problems with focus and attention. Other signs include uncoordinated or slow movement, tremors, and rigidity (parkinsonism).

Alzheimer's disease is the most common cause of progressive dementia in older adults. Alzheimer’s disease is characterized by progressive loss of memory and cognitive function. The disease can be sporadic or may be familial. Prevalence increases with age, with as many as 20% of individuals over 85 years of age being affected. Early onset Alzheimer’s disease is associated with specific gene deficits.

Pathologic changes in the brains of those with Alzheimer’s disease include deposits of beta-amyloid peptide in the cerebral cortex which form extracellular plaques and lesions as well as intraneuronal fibrillary tangles of the tau protein. With these changes, there is progressive loss of cholinergic neurons. Some evidence also indicates glutamate excitation may contribute to neuronal cell death.

Most treatment methods have relied upon cholinomimetic drugs to increase acetylcholine. Specifically, drugs acting as cholinesterase inhibitors, e.g., donepezil, rivastigmine and galantamine are commonly used. Of course, these drugs also cause typical cholinergic-related adverse effects (e.g, bronchoconstriction, diarrhea, etc.).

The excitotoxic effects of glutamate transmission is the target of the drug memantine, which is a noncompetitive blocker of NMDA receptors. 

Aducanumab and lecanemab are newly approved monoclonal antibodies that target beta-amyloid. Aducanumab targets beta-amyloid and removes it from the brain.  Lecanemab targets a different structure of beta-amyloid and blocks formation of amyloid plaques. Both drugs decrease beta-amyloid plaques in the brain. They are administered intravenously. In clinical trials, 41% of patients experienced brain swelling or bleeding with aducanumab; lecanemab was associated with brain edema in 13% of patients. Regular MRIs are needed (e.g., every 6 months). These drugs are expensive and have been the source of controversy since they were approved based upon surrogate endpoints (e.g., fewer beta-amyloid deposits) rather than clinical outcomes. After its approval, lecanemab was been found to slow progression of the disease slightly. 

Educational Activity for the classroom:

You are the Chief Medical Officer for a healthcare provider (e.g., Blue Cross/Blue Shield Medical Advantage program). You’ve convened a team of experts (your classroom work group} to decide which, if any, of the drugs approved to treat Alzheimers disease will be covered for subscribers to your health plan.

The 4 drugs for you to consider are:  donepezil, memantine, aducanumab and lecanemab. Complete the table below, to help inform your decision.