The authors have declared that no competing interests exist.
Controversy exists about definition of agitation and especially about inclusion of aggression as a part of agitation in people with dementia.
Papers describing neurobiological indices related to behavioral symptoms of dementia were reviewed. Papers comparing indices in persons exhibiting aggression and persons exhibiting agitation were selected for this review.
The survey found seven papers which compared neuroanatomical indices and three papers which compared neurochemical indices. The neuroanatomical indices differentiating agitation and aggression included changes in brain perfusion, sizes of brain areas, distribution of neurofibrillary tangles, and white matter changes. The neurochemical indices differentiating agitation and aggression included relationships with neurotransmitter variables and the cell count in the locus coeruleus.
Despite the small number of papers and some methodological problems, the presented information clearly indicates that aggression and agitation are two distinct unrelated syndromes in persons with dementia.
Behavioral and psychiatric symptoms of dementia are very common and are often more distressing than consequences of cognitive impairment. These symptoms are associated with increased healthcare use, earlier institutionalization
Separation is of aggression and agitation is based on different circumstances present when these syndromes occur and several rating scales, including MDS 3.0 make this distinction
Medline was searched using “dementia AND behavior AND brain changes AND people”. The search identified 811 publications. By reviewing abstracts of these publications,
Scale | Aggression | Agitation |
Cohen-Mansfield Agitation Inventory (CMAI) |
Physical /AggressiveHitting (including self) Kicking. Grabbing onto people. Pushing. Throwing things. Biting. Scratching. Spitting. Hurting self or others. Tearing things or destroying property. Making physical sexual advancesVerbal /AggressiveScreaming. Making verbal sexual advances. Cursing or verbal aggression | Physical /Non-AggressivePace, aimless wandering. Inappropriate dress or disrobing. Trying to get to a different place. Intentional falling. Eating / drinking inappropriate substance. Handling things inappropriately. Hiding things. Hoarding things. Performing repetitive mannerisms. General restlessnessVerbal/Non-aggressiveRepetitive sentences or questions. Strange noises (weird laughter or crying). Complaining. Negativism. Constant unwarranted request for attention or help |
Neuropsychiatric Inventory (NPI) |
C. AGITATION/AGGRESSIONUpset with caregiver; resists ADL’sStubbornnessUncooperative; resists help Hard to handleCursing or shouting angrily Slams doors; kicks, throws thingsHits, harms others |
J. ABERRANT MOTOR BEHAVIORPaces without purposeOpens or unpacks closets or drawersRepeatedly dresses and undressesRepetitive activities or “habits”Handling, picking, wrapping behaviorExcessively fidgety |
Present Behavioral Evaluation (PBE) |
2. Aggressive behaviourAggressive resistance - resisting attempts to help or being uncooperative, usually in the context of intimate carePhysical aggression - eg hitting, kicking, scratching, pushing or spitting in an aggressive mannerVerbal aggression and hostility -speaking in an aggressive or cross tone or voice raised in anger | 1. OveractivityWalking more - walking distinctly more than is normalAimless walking - walking aimlessly without an obvious reasonTrailing and checking - needing frequent reassurance of presence of carer either by following or frequently checking location of carer |
Stockton Geriatric Rating Scale (SGRS) |
Behaviour resulting in or liable to result in actual physical harm to another person | Walking more, aimless walking, and trailing and checking |
There were several differences in neurobiological substrates found in persons who exhibited agitation and in persons who exhibited aggression. These differences were detected in both clinical and post-mortem studies (
Clinical studies | Scale used | Reference | |
Aggression | Agitation | ||
Hypoperfusion in the left anterior temporal, bilateral dorsofrontal and right parietal. cortices | No correlation with perfusion | NPI |
|
Termporal lobe atrophy | Widening of Silvian fissure | SGRS |
|
Not related to any tissue loss | Tissue loss in the right dorsal anterior cingulate cortex and left premotor cortex | NPI |
|
No relationship with size of amygdala | Amygdala atrophy | NPI |
|
No correlation | Correlated with white matter hyperintensities | NPI |
|
Post-mortem studies | |||
Increased NFTs in hippocampus | No correlation with hippocampal morphology | PBE |
|
Increased NFTs in the left orbitofrontal cortex in left anterior cingulate | Increased NFTs in the left orbitofrontal cortex only | NPI |
|
Decreased acetylcholine and choline acetyltransferase in frontal and temporal cortices | Decreased serotonin levels in frontal cortex | PBE |
|
No correlation | Correlations with neurotransmitter variables in hippocampus and cerebellum | CMAI |
|
Low cell count of the locus coeruleus | No correlation with cell count | PBE |
|
Neuropsychiatric Inventory
Stockton Geriatric Rating Scale (SGRS)
Present Behavioral Examination (PBE)
Cohen-Mansfield Agitation Inventory (CMAI)
Domain | Method for data collection | |
Proxy report | Observation | |
Single behavioral syndrome | Ryden Aggression Scale |
Scale for Observation of Agitation in Persons with DAT dementia of the Alzheimer type (SOAPD) |
Caretaker obstreperous-behavior rating assessment (COBRA) scale |
Resistiveness to Care – Dementia of the Alzheimer Type (RTC-DAT) scale |
|
All behaviors | Cohen-Mansfield Agitation Inventory (CMAI) |
|
Present Behavioral Examination (PBE) |
||
Comprehensive assessment | NPI |
Minimum Data Set 3.0, E0300 Overall Presence of Behavioral Symptoms, E0800 Rejection of Care |
Differences between aggression and agitation included changes in brain perfusion, differences in brain atrophy, and white matter changes. Hirono et al
Burns et al
Rosen et al
Similarly, Poulin et al
Aggression and agitation were also separated in a white matter study. Hirono et al.
Two studies reported increased load of neurofibrillary tangles (NFTs) in aggressive subjects with dementia. Lai et al
Tekin et al
There are several neurotransmitters that are affected differently by aggression and agitation. Garcia-Alloza et al
Vermeiren et al
Differential involvement of the noradrenergic system is suggested by cell count in the locus coeruleus. Matthews et al
The confusion regarding terminology of behavioral symptoms of dementia is not new and is perpetuated by the multitude of instruments used to evaluate these symptoms. A recent review evaluated 83 instruments developed to measure behavioral and psychological symptoms of dementia.
The first scales, that evaluated neurobiological substrate, were Cohen-Mansfield Agitation Inventory (CMAI)
Several efforts were made to simplify the response structure of NPI but they usually resulted in emphasizing psychiatric conditions instead of differentiating behavioral symptoms
Despite this acknowledgement that agitation and aggression are two separate syndromes, a group of experts, convened by the International Psychogeriatric Association (IPA), developed provisional consensus stating that agitation is manifested by excessive motor activity, verbal aggression, or physical aggression
Distinction between agitation and aggression is important for both non-pharmacological and pharmacological management of behavioral symptoms of dementia. Non-pharmacological strategies used for treatment of agitation need to concentrate on providing meaningful activities because agitation is often caused by boredom of persons with dementia
There is a danger that a medication may be developed and approved by the FDA with indication of agitation without recognizing the difference between agitation and aggression. It is important to realize that Minimum Data Set 3.0 does not contain the term agitation. It is distinguishing behavioral symptoms, according to the involvement of others, into behaviors directed towards others and behaviors not directed towards others. Aggression by definition involves others, while damaging equipment may be just an escalation of agitation (e.g., damaging a chair by restlessness), not directed toward others and not real aggression. Providers of care for persons with dementia need a clear connection between their evaluations and research results, and a confusing concept of agitation that includes aggression is not going to help the in providing appropriate care for persons with dementia who exhibit behavioral symptoms.
There are some limitations of this study. The main one is that there is not enough information available to construct a mechanism underlying neurobiological mechanisms related to agitation and aggression. Therefore, this paper is limited to pointing out that the neurobiological indices are differentiating these two syndromes. The second limitation is the use of results obtained with scales that rely on proxy reports. These scales do not provide information about the context in which these behaviors occurred. Thus, the same person may be considered to exhibit both agitation and aggression, but these behaviors may occur in different times and different contexts. However, despite these limitations, data presented in this review indicate that agitation and aggression should be considered as two independent syndromes. The third limitation is that subjects involved in these studies had several causes of dementia. However, large-scale studies showed no difference in the prevalence of neuropsychiatric behaviors between Alzheimer's disease and non-Alzheimer's disease dementias