Why Is Agitation a Symptom of Alzheimer's Disease?

In my limited experience, young kids climb furniture, try to eat rocks, ignore safety advice, and seem to be unable to hear instructions they disagree with (like “time to get ready for bed,” as a random example). This causes some parents significant anxiety, which will frequently give way to agitation. For many parents, this agitation takes the form of hard stares, grimaces, foot tapping, and heavy sighs. Agitation can be a difficult emotion to cope with and even more difficult when you have trouble communicating what is so agitating. Unfortunately, it’s not just limited to people with young kids; agitation is a significant, frustrating, and difficult condition for people with Alzheimer’s disease (AD).

Dementia is a condition that impairs the brain and can interfere with memory, thinking, behavior, and the ability to manage daily activities. Approximately one-third of adults over age 85 have dementia, with Alzheimer’s disease being the most common form.^[1,2] Agitation is a common complication, affecting around 30%-50% of all people with AD, and 80% of nursing home residents with Alzheimer’s.^[1,3] Agitation is the external expression of emotional distress, often characterized by restlessness, exaggerated and undirected fidgeting or physical activity, irritability, and often aggressive behavior.^[1,3] Alzheimer’s patients who express agitation tend to have worse outcomes, including increased suffering and hospitalization.^[2] Agitation can also make it harder to care for people with Alzheimer’s, both because family members struggle to cope with a changing personality and because agitation and aggression can be an added physical and emotional struggle for caregivers.^[2]

Research finds that metabolic changes, acute medical and psychological problems like COVID-19, pain, sleep disorders, and problems with the senses may increase the risk of developing agitation.^[3] A more clear-cut leading theory is that anxiety seems to pave the way for agitation (just like parents with small children experience).^[1] Researchers found that those who had high anxiety in preclinical (non-diagnosed) Alzheimer’s disease tended to “replace” this anxiety with agitation as the disease progressed.^[1] Other scientists think agitation may be the external expression of anxiety.^[3]

Studies that look inside the brain support the link between anxiety and agitation.^[4] The “agitation circuit” in the brain consists of parts of the front (frontal and orbitofrontal cortex), mid-back (anterior cingulate cortex), and deep center (amygdala and insula) of the brain; areas that are also associated with anxiety.^[4] Alzheimer’s disease can involve dysfunction in the frontal and mid-back sections of the brain, reduced control between “agitation circuit” brain areas, decreased blood flow to areas of the brain that process external stimuli, and imbalances of communication molecules called neurotransmitters.^[1,3,4] As a result, the brain's “agitation circuit” can become overactive, lose its ability to self-regulate, and worsen with sensory changes like sunset, low light, and modifications to medications^[3]

So, agitation is common among those with Alzheimer’s, hard to cope with, and makes giving care more difficult. Can anything be done? The first line of treatment is patient-centered care.^[3] This non-pharmaceutical approach to care has the health practitioner and patient work as a team to meet the patient’s needs.^[3] Patient-centered care considers the patient’s history (including disease history) and lifestyle to promote a positive social environment that reduces anxiety and agitation.^[3] This may include socialization to reduce boredom and music intervention.^[3] Patient-centered care can be difficult and labor-intensive, especially when a patient can’t communicate or is hospital-bound.^[3] Needs-driven care attends to pain and reduces complications of agitation, but is also difficult when someone has trouble communicating.^[3] After non-pharmaceutical methods have been tried, some patients still need more help and are prescribed medications.^[3] Atypical antipsychotics like brexpiprazole and SSRI antidepressants may be prescribed, though these may come with side effects including sedation, nausea, appetite changes, insomnia, and increased fall risk.^[1,2] Sedation can be a particularly devastating side effect for family members, as it reduces the already-low communication many people with AD have.^[2] Clinical trials are actively looking into new medications that will hopefully reduce agitation with fewer side effects. If these are successful, people with Alzheimer’s disease may have a chance to reduce their agitation - no kidding!

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] Ostergaard JR. A new perspective on agitation in Alzheimer’s disease: a potential paradigm shift. International Journal of Molecular Sciences. 2025 Apr 4;26(7):3370. https://doi.org/10.3390/ijms26073370

[2] Sadowska K, Turnwald M, O'Neil T, Maust DT, Gerlach LB. Behavioral symptoms and treatment challenges for patients living with dementia: Hospice clinician and caregiver perspectives. Journal of the American Geriatrics Society. 2025 Apr;73(4):1094-104. https://doi.org/10.1111/jgs.19320

[3] Carrarini C, Russo M, Dono F, Barbone F, Rispoli MG, Ferri L, Di Pietro M, Digiovanni A, Ajdinaj P, Speranza R, Granzotto A. Agitation and dementia: prevention and treatment strategies in acute and chronic conditions. Frontiers in neurology. 2021 Apr 16;12:644317.

[4] Liu KY, Stringer AE, Reeves SJ, Howard RJ. The neurochemistry of agitation in Alzheimer’s disease: a systematic review. Ageing research reviews. 2018 May 1;43:99-107. https://doi.org/10.1016/j.arr.2018.03.003