Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder.   Initially, a person with AD may suffer memory lapses, such as forgetting familiar words or the location of everyday objects.  With progressive neuronal loss, a person may develop changes in their personality and behavior and show severe cognitive impairment and memory loss.  The individual may eventually lose the ability to respond to their environment, to carry on a conversation and to control movement.

More than 5 million Americans are living with AD dementia in 2020.  Two-thirds of Americans over age 65 with AD dementia (3.6 million) are women.

Agitation is a disabling phenomenon that occurs commonly in the course of AD, particularly later in the illness.   People with AD may get upset or angry easily and lash out at others for no obvious reason. They may shout, curse and scream, and may insult or become physical with caregivers.   Agitation, characterized by excessive verbal and/or motor behavior and disinhibition can escalate to aggression, which can be either verbal (vicious cursing and threats) or physical (toward objects or people).  Agitation and aggression are distressing for the individual and often confer risk to them and to others, earlier nursing home placement, and increased mortality.

There are currently no therapies approved by the FDA for the treatment of agitation in patients with AD.  Many physicians use anti-psychotic drugs like quetiapine and risperidone for the treatment of AD agitation, but despite some reported evidence efficacy, these drugs are associated with a significant side effect liability.

Investigations into the underlying neuropathology of AD indicate that the dopaminergic and serotonergic systems contribute to agitation and aggression.  At MapLight, we are taking a targeted approach. Rather than attempting to change dopamine or serotonin release across the brain, our approach will target a small subset of neurons that misfire in AD.  By focusing our therapeutic strategies on specific populations of neurons that become dysfunctional during AD, our treatments will have both improved efficacy and fewer side effects.