The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia.

Abstract

To identify neurochemical correlates of behavioral and psychological signs and symptoms of dementia (BPSD), we set up a prospective study. Patients with probable Alzheimer's disease (AD) (n=181), mixed dementia (MXD) (n=28), frontotemporal dementia (FTD) (n=25) and dementia with Lewy bodies (DLB) (n=24) were included. At inclusion, all patients underwent lumbar puncture, neuropsychological examination and behavioral assessment (battery of behavioral assessment scales). Cerebrospinal fluid (CSF) levels of norepinephrine and of (nor)epinephrine (MHPG), serotonin (5HIAA) and dopamine (DOPAC, HVA) metabolites were determined by HPLC and electrochemical detection. Spearman Rank-Order followed by Bonferroni correction was used for calculating correlations. In FTD patients, CSF norepinephrine levels were positively correlated with dementia severity (r=0.539; p=0.021). CSF DOPAC levels were correlated with BPSD in general (r=0.537; p=0.007), associated caregiver burden (r=0.567; p=0.004) and agitated and aggressive behavior (r=0.568; p=0.004). In a subgroup of FTD patients who did not receive psychotropic pharmacological treatment, a strong correlation between CSF HVA/5HIAA ratios (reflecting serotonergic modulation of dopaminergic neurotransmission) and aggressive behavior (r=0.758; p=0.009) was found. In MXD patients, (verbally) agitated behavior was positively associated with the turnover of norepinephrine (r=0.633; p=0.002). No significant correlations were found in AD and DLB groups. In FTD, increased activity of dopaminergic neurotransmission and altered serotonergic modulation of dopaminergic neurotransmission is associated with agitated and aggressive behavior respectively. This study demonstrated that neurochemical mechanisms underlying the pathophysiology of BPSD are both BPSD-specific and disease-specific which might have implications for future development of new and more selective pharmacological treatments of BPSD.

• Authors: Sebastiaan Engelborghs, Ellen Vloeberghs, Nathalie Le Bastard, Michael Van Buggenhout, Peter Mariën, Nore Somers, Guy Nagels, Barbara A Pickut, Peter P De Deyn
• Journal: Neurochemistry international (Neurochem Int) Vol. 52 Issue 6 Pg. 1052-60 (May 2008) ISSN: 0197-0186 [Print] England
• PMID: 18093695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serotonin
• Dopamine
• Norepinephrine
• Epinephrine

Topics

• Aged
• Aged, 80 and over
• Aggression (physiology)
• Alzheimer Disease (metabolism, physiopathology)
• Brain (metabolism, physiopathology)
• Brain Chemistry (physiology)
• Chromatography, High Pressure Liquid
• Dementia (cerebrospinal fluid, complications, physiopathology)
• Dopamine (analysis, cerebrospinal fluid)
• Epinephrine (analysis, cerebrospinal fluid)
• Female
• Humans
• Lewy Body Disease (metabolism, physiopathology)
• Male
• Mental Disorders (cerebrospinal fluid, etiology, physiopathology)
• Neuropsychological Tests
• Norepinephrine (analysis, cerebrospinal fluid)
• Prospective Studies
• Psychomotor Agitation (cerebrospinal fluid, etiology, physiopathology)
• Serotonin (analysis, cerebrospinal fluid)
• Synaptic Transmission (physiology)