Agitation in Alzheimer’s disease: From assessment to therapeutics

Table 1 Clinical and research definition of agitation in cognitive disorders according to the International Psychogeriatric Association 2024 Consensus

Criterion	Features
Criterion A	The patient meets criteria for cognitive impairment or dementia syndrome regardless of its etiology
Criterion B	The patient exhibits at least one type of behavior [(1) Excessive motor activity; (2) Verbal aggression; and (3) Physical aggression)] associated with observed or inferred evidence of emotional distress (e.g., irritability, anger). This behavior has been persistent or frequent for a minimum of two weeks or the behavior represents a marked change from the patient’s usual behavior
Criterion C	Behaviors are severe and associated with excess distress or produce excess disability, including at least one of the following significant impairments: (1) Interpersonal relationships; (2) Other aspects of social functioning; and (3) Ability to perform or participate in daily living activities
Criterion D	While comorbid conditions may be present, the agitation is not attributable solely to another psychiatric disorder, medical condition, including delirium, suboptimal care conditions, or the physiological effects of a substance

Adapted from Sano et al[13].

Table 2 Modifiable and non-modifiable risk factors for agitation in cognitive disorders

Modifiable	Non-modifiable
Acute environmental changes (e.g., changes in caregiver and daily routine with over- and/or under-stimulation)	Advanced dementia
Caregiver attitude and interaction	History of psychiatric disorders, including antisocial and borderline personality traits or disorders
Current psychiatric disorder (e.g., depression)	Impulsivity
Physical or somatic illness (e.g., pain, thirst, hunger)	Impaired insight
Prescribed or illicit drugs (e.g., antihistamines, anticholinergics, alcohol)	Sensory impairments

Table 3 Clinical assessment tools for agitation in older adults with Alzheimer’s disease

Assessment tool	Dimensions evaluated	Application stage	Strengths	Limitations
NPI	Multiple behavioral and psychological domains, including apathy, anxiety, agitation/aggression, dysphoria/depression, delusions, hallucinations, among others	Different stages of AD	Broad coverage of symptoms; flexibility: Multiple versions suitable for different applications; available for rapid screening (NPI-Q) in busy clinical settings	Limited assessment of different agitation-related behaviors; the original version (NPI) is time-consuming
BEHAVE-AD	Multiple behavioral and psychological domains, including paranoid/delusional ideation, hallucination, activity disturbances, aggressiveness, among others	Different stages of AD, but better suitable for later ones (domains selected to reflect behaviors likely to respond to medications)	Broad coverage of symptoms	Less detailed than agitation-specific tools; less practical in time-constrained settings
CMAI	Different physical and verbal, aggressive and non-aggressive behaviors	Advanced stages of AD (developed to assess behaviors of older adults living in nursing homes)	Comprehensive characterization of agitation-related behaviors	Narrower scope; does not cover other behavioral and psychological symptoms

NPI: Neuropsychiatric Inventory; NPI-Q: Neuropsychiatric Inventory Questionnaire; BEHAVE-AD: Behavioral pathology in Alzheimer’s disease Rating Scale; CMAI: Cohen-Mansfield Agitation Inventory; AD: Alzheimer’s disease.