An imbalance of top-down executive function and bottom-up emotional drive is thought to be associated with agitated behaviors1-3
Appropriate behavior relies on the balance between top-down executive function (prefrontal cortex) and bottom-up emotional drive (amygdala).1,4,5
Loss of top-down executive function and elevated bottom-up emotional drive create an imbalance and can lead to agitated behaviors.1,4,5
AAD is associated with hypoactivity in the prefrontal cortex and hyperactivity in the amygdala. Neuronal loss may lead to norepinephrine, serotonin, and dopamine (NSD) neurotransmitter systems dysfunction, resulting in this imbalance of top-down executive function and bottom-up emotional drive that is associated with agitated behaviors.2,3,6-8
AAD, Agitation in Alzheimer’s Dementia; PFC, prefrontal cortex.
References: 1. Rosenberg PB, Nowrangi MA, Lyketsos CG. Neuropsychiatric symptoms in Alzheimer's disease: What might be associated brain circuits? Mol Aspects Med. 2015;43-44:25-37. 2. Wright CI, Dickerson BC, Feczko E, Negeira A, Williams D. A functional magnetic resonance imaging study of amygdala responses to human faces in aging and mild Alzheimer's disease. Biol Psychiatry. 2007;62(12):1388-1395. 3. Banno K, Nakaaki S, Sato J, et al. Neural basis of three dimensions of agitated behaviors in patients with Alzheimer disease. Neuropsychiatr Dis Treat. 2014;10:339-348. 4. Arnsten AFT, Raskind MA, Taylor FB, Connor DF. The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder. Neurobiol Stress. 2015;1:89-99. 5. Carrarini C, Russo M, Dono F, et al. Agitation and dementia: Prevention and treatment strategies in acute and chronic conditions. Front Neurol. 2021;12:644317. 6. Hirono N, Mega MS, Dinov ID, Mishkin F, Cummings JL. Left frontotemporal hypoperfusion is associated with aggression in patients with dementia. Arch Neurol. 2000;57(6):861-866. 7. Ng KP, Chiew H, Rosa-Neto P, Kandiah N, Ismail Z, Gauthier S. Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer's disease and cognitively unimpaired individuals. Transl Neurodegener. 2021;10(1):11. 8. Lanctôt KL, Herrmann N, Mazzotta P. Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci. 2001;13(1):5-21.