Abstract
Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.
Highlights
Agitation is a common behavioral disturbance featuring exaggerated motor activity and verbal and/or physical aggressiveness, severe enough to impair social relations and daily living activities [1].Agitation is observed in up to 70% of patients with cognitive decline, and its incidence is higher in moderate to severe stages of the disease [2]
The present review provides a toolbox for the detection, prevention, and therapeutical management of acute and chronic agitation in patients suffering from neurodegenerative conditions
The recently published European Academy of Neurology (EAN) recommendation on the management of issues in dementia, including agitation, reports that individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others
Summary
Agitation is a common behavioral disturbance featuring exaggerated motor activity and verbal and/or physical aggressiveness, severe enough to impair social relations and daily living activities [1]. The occurrence of agitation is related to frontal lobe dysfunctions [10, 11] and, in particular, to an abnormal activation of the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) [12]. This notion has been supported by postmortem studies [12, 13] showing the large presence of neurofibrillary tangles in the OFC and ACC of patients with the frontal variant of AD. The present review provides a toolbox for the detection, prevention, and therapeutical management of acute and chronic agitation in patients suffering from neurodegenerative conditions
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