Dementia Is Common and Somewhat Treatable

Approximately 11% of Americans 65 years or older have dementia, which leads to progressive cognitive function decline that impairs activities of daily living.^1,2 That count of 6.2 million may reach 12 million by 2040.^1,3 Symptoms of dementia include declining language memory and problem-solving impairments, with women at greater risk than men.^1,4 Risk of dementia is highest among individuals older than 65 years.⁴

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Experts have now identified 10 categories of dementia (Table 1²), with 2 most common types.2 Alzheimer disease is closely associated with amyloid-β accumulation, τ protein hyperphosphorylation, and cholinergic deficit.^5-7 Brain trauma (ischemia-induced tissue damage or microvascular diseases) can lead to vascular dementia.⁸

Most patients with dementia eventually experience at least 1 behavioral and psychological symptom of dementia (BPSD) that causes considerable unease^.9-11 BPSD manifests most commonly as apathy, agitation, aggression, and irritability but can also include abnormal body movements, anxiety, delusions, depression, disinhibition, hallucinations, and sleep or appetite changes.11 BPSD emanates from acetylcholine, dopamine, and serotonin neurotransmission dysregulation in Alzheimer disease.¹¹ Low acetylcholine and dopamine levels can precipitate psychosis, whereas a decline in serotonergic neurotransmission in the brain leads to aggression, agitation, anxiety, depression, and restlessness.^12,13

Treating Cognitive Symptoms

Medications used to treat the cognitive symptoms of dementia include cholinesterase inhibitors such as donepezil (Aricept; Eisai), galantamine (Razadyne; Janssen), and rivastigmine (Exelon; Novartis) as well as the N-methyl-D-aspartate (NMDA) receptor antagonist memantine (Namenda; AbbVie).14 These drugs slow disease progression but do not cure dementia. It appears that cholinesterase inhibitors may delay the use of medication to treat BPSD in addition to slowing cognitive symptoms.¹⁵

Cholinesterase inhibitors decrease central acetylcholine metabolism, thereby increasing its synaptic availability, which may improve memory and language.¹⁶ In addition to prescribing donepezil and rivastigmine in all stages of Alzheimer disease, prescribers use them to improve cognitive function in Lewy body dementia and Parkinson disease.^17,18 Cholinesterase inhibitors’ adverse effects include nausea, vomiting, bradycardia, hypotension, diarrhea, and dizziness.¹⁹

Memantine inhibits glutamate binding at NMDA receptors and decreases neuronal damage. In moderate to severe Alzheimer disease, prescribers sometimes add memantine to cholinesterase inhibitors or use it as monotherapy. Memantine’s adverse effects include confusion, dizziness, and headache. Dizziness associated with both drug classes has been linked to increased fall risk.¹⁹

Treatment of BPSD

Prescribers use many medications to manage BPSD, as described in Table 2.^20-35 Most of these are used off-label and with limited evidence.

Nonpharmacologic Interventions

Social contact, activities (exercise and group programs), sensory stimulation, and neurocognitive technology may lessen some BPSD. Clinicians should also help eliminate or manage the underlying causes of BPSD (eg, confusing surroundings, pain, poor eyesight or hearing, change in caregiver). Other interventions include aerobic exercises and music therapy.³⁶

Conclusion

With little high-quality data available to guide treatment for patients with dementia, many patients need a trial-anderror approach to disease management. Pharmacists can help choose medications for predominant symptoms and monitor for response and adverse effects.

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