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Review
. 2019 Jun 21:704:36-44.
doi: 10.1016/j.neulet.2019.03.050. Epub 2019 Apr 1.

Serotonergic system, cognition, and BPSD in Alzheimer's disease

Saikat Chakraborty  1 , Jack C Lennon  1 , Sridhar A Malkaram  2 , Yan Zeng  3 , Daniel W Fisher  1 , Hongxin Dong  4
Affiliations
Review

Serotonergic system, cognition, and BPSD in Alzheimer's disease

Saikat Chakraborty et al. Neurosci Lett. .

Abstract

Behavioral and Psychological Symptoms of Dementia (BPSD), present in almost 90% of patients with Alzheimer's Disease (AD), cause extensive impairment leading to reduced independence and inability to complete activities of daily living. Though BPSD includes a wide range of symptoms, such as agitation, aggression, disinhibition, anxiety, depression, apathy, delusions, and hallucinations. Certain BPSD in AD co-present and can be clustered into distinct domains based on their frequency of co-occurrence. As these BPSD are so pervasive in any stages of AD, the disease may be better characterized as a disorder of heterogeneous degenerative symptoms across a number of symptom domains, with the most prominent domain comprising memory and cognitive deficits. Importantly, there are no FDA-approved drugs to treat these BPSD, and new approaches must be considered to develop effective treatments for AD patients. The biogenic monoamine 5-hydroxytryptamine (5-HT), or serotonin, works as both a neurotransmitter and neuromodulator, which has been tied to cognitive decline and multiple BPSD domains. This review summarizes the evidence for specific serotonergic system alterations across some of the well-studied cognitive, behavioral, and psychiatric domains. Though differences in overall serotonergic transmission occur in AD, circuit-specific alterations in individual 5-HT receptors (5-HTRs) are likely linked to the heterogeneous presentation of BPSD in AD.

Keywords: 5-HT receptors (5-HTRs); 5-hydroxytryptamine (5-HT); Alzheimer's disease; Behavioral and psychological symptoms of dementia (BPSD).

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Figures

Figure 1.
Figure 1.. Serotonin Receptor Distribution in Hippocampus and Prefrontal Cortex Associated with Cognition
Abbreviations: LTP = Long-term potentiation; STM = Short-term memory; LTM = Long-term memory; OCD = Obsessive-Compulsive Disoder
Figure 2.
Figure 2.. Serotonin receptors and their bidirectional associations with BPSD.
Abbreviations: NAc = Nucleus accumben; AAP = Atypical antipsychotic; BPSD = Behavioral and psychological symptoms of dementia; HIDA = Hyperactivity/irritation/disinhibition/aggression
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