Understanding Agitation in Alzheimer's: Why Memory Care Isn't Enough – with Carolyn Clevenger, GNP

Agitation in Alzheimer disease (AD) is a critical yet frequently misunderstood clinical challenge that affects a substantial proportion of patients throughout the disease trajectory, Carolyn Clevenger, GNP, professor of nursing at Emory University's Nell Hodgson Woodruff School of Nursing, explained during a recent interview with Patient Care.^© Research indicates that approximately 45% of community-dwelling patients with AD experience agitation,¹ while more than 90% of individuals with the disorder develop behavioral and neuropsychiatric symptoms² during the course of their illness. Despite its prevalence, agitation remains underrecognized and often conflated with cognitive decline itself.

Clevenger pointed to fundamental differences in the pathophysiology of agitation compared with that of memory impairment. Evidence suggests that agitation in AD involves noradrenergic hyperactivity combined with serotonergic deficits and dysregulated striatal dopamine release,³ conditions that affect brain regions responsible for emotional regulation rather than memory formation. This distinction has profound clinical implications, Clevenger stressed: treatments targeting acetylcholine and hippocampal function for cognitive symptoms do not address the monoamine neurotransmitter dysregulation underlying agitation. In the short video segment above, Clevenger explains why agitation requires distinct recognition and management strategies separate from cognitive interventions, challenging the common misconception that a unified care approach suffices for all manifestations of AD.

The following transcript has been lightly edited for style and flow.

Patient Care: Many caregivers of people living with Alzheimer disease don't realize that agitation is a separate but related condition, distinctly different from cognitive decline. Three quarters of the caregivers in the survey (The Agitation Blind Spot in Alzheimer's Care) responded that they believe agitation requires the same care approach as memory loss. Would you talk more about that?

Carolyn Clevenger, GNP: You're absolutely right. Our brains are so complex, and the areas where you form memories are different from the parts where you regulate emotions. The reality of Alzheimer's disease is that you have not only cognitive symptoms, thinking, processing, remembering, judging, reasoning, but you also have psychiatric symptoms and changes, which then lead to functional changes, meaning you need more help doing activities of daily living. So there are three parts to that dementia syndrome in [Alzheimer] disease.

The changes happening in the brain that are causing those cognitive changes, like memory and thinking and processing, that's a different part of the brain, different processes than what's involved in the pathology of agitation. The pathology of agitation is affecting the parts of the brain where we express and regulate emotions. Some of the deep brain structures are where we generate those emotions, and the upper part of the brain, the cortex, is where you then control them.

What we're seeing is a dysregulation of neurotransmitters—serotonin, norepinephrine, and dopamine—where sometimes we have overproduction or production targeting the wrong parts of the brain, which then leads to these agitation symptoms. So if you have a treatment, whether medication or non-medication, that is addressing the changes in neurotransmitters and parts of the brain that control memory, if you're trying to increase acetylcholine and target the hippocampus, that's very different than trying to target serotonin, norepinephrine, and dopamine in a different area of the brain.

When you think about it from the mechanism of action, both the mechanism of the symptom, what's generating the symptom, and how we would treat it, it seems more logical to understand why just managing cognitive symptoms is probably not going to help the management of these neuropsychiatric symptoms, specifically agitation.