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

Chakraborty, Saikat; Lennon, Jack C.; Malkaram, Sridhar A.; Zeng, Yan; Fisher, Daniel; Dong, Hongxin

doi:10.1016/j.neulet.2019.03.050

Cited by 81 publications

(87 citation statements)

References 149 publications

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“…Although sundowning has been studied for several decades, its cause remains unclear. Evidence from basic research (Bedrosian and Nelson, 2013;Todd et al, 2018), along with pathological findings from AD patients (Wang et al, 2015;Erskine et al, 2016;Chakraborty et al, 2019), suggests several pathways that might be involved in the circadian dysfunction, and agitation and aggression, underlying sundowning. There is a strong association between circadian rhythms and emotional regulation (Hood and Amir, 2018;Ketchesin et al, 2020), and the shared circuitry between these two systems presents potential candidates for such pathology-related dysfunction.…”

Section: Resultsmentioning

confidence: 99%

“…There is also substantial evidence for a role in the disruption of serotonergic neurons in AD (Rodriguez et al, 2012;Vakalopoulos, 2017;Chakraborty et al, 2019), and serotonin is also known to play role in circadian regulation (Ciarleglio et al, 2011;Daut and Fonken, 2019). Several studies have suggested a dense serotonergic input from the midbrain raphe complex to the SCN and SPZ (see Figure 1).…”

Section: Serotonergic Inputs To the Circadian Systemmentioning

confidence: 99%

“…So, its possible that AD-related disruptions in serotonergic signaling also underlie overall levels of aggression, as well as differences at certain times of the day. Indeed, several groups have reported serotonergic deficiencies in AD that were associated with either increased circadian dysfunction or behavioral aggression (Lai et al, 2003;Vermeiren et al, 2014;Chakraborty et al, 2019).…”

Section: Serotonergic Inputs To the Circadian Systemmentioning

confidence: 99%

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Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

Todd

2020

Front. Neurosci.

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Patients with Alzheimer's disease (AD) and related dementias are commonly reported to exhibit aggressive behavior and other emotional behavioral disturbances, which create a tremendous caretaker burden. There has been an abundance of work highlighting the importance of circadian function on mood and emotional behavioral regulation, and recent evidence demonstrates that a specific hypothalamic pathway links the circadian system to neurons that modulate aggressive behavior, regulating the propensity for aggression across the day. Such shared circuitry may have important ramifications for clarifying the complex interactions underlying "sundowning syndrome," a poorly understood (and even controversial) clinical phenomenon in AD and dementia patients that is characterized by agitation, aggression, and delirium during the late afternoon and early evening hours. The goal of this review is to highlight the potential output and input pathways of the circadian system that may underlie circadian dysfunction and behavioral aggression associated with sundowning syndrome, and to discuss possible ways these pathways might inform specific interventions for treatment. Moreover, the apparent bidirectional relationship between chronic disruptions of circadian and sleepwake regulation and the pathology and symptoms of AD suggest that understanding the role of these circuits in such neurobehavioral pathologies could lead to better diagnostic or even preventive measures.

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Section: Resultsmentioning

confidence: 99%

Section: Serotonergic Inputs To the Circadian Systemmentioning

confidence: 99%

Section: Serotonergic Inputs To the Circadian Systemmentioning

confidence: 99%

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Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

Todd

2020

Front. Neurosci.

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“…FTD has been found to have the highest incidence of suicide, followed by vascular dementia and Lewy body dementia (Lai et al, 2018), the latter of which is classified with PD dementia as alpha-synucleinopathies (Spillantini and Goedert, 2000). Further, behavioral and psychological symptoms of dementia (BPSD) have been found to be present in nearly 90% of AD patients, which both exacerbate symptoms, and increase the rate of disease progression (Chakraborty et al, 2019). BPSD align with well-established suicide endophenotypes, such as depression, anxiety, aggression, impulsivity, hyperactivity, disinhibition, and decision-making (Gould et al, 2017).…”

Section: Suicide As a Multidimensional Processmentioning

confidence: 99%

Etiopathogenesis of Suicide: A Conceptual Analysis of Risk and Prevention Within a Comprehensive, Deterministic Model

Lennon

2019

Front. Psychol.

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Suicide is a rising global health concern receiving disproportionate attention in comparison to other health conditions. In spite of substantial technological and scientific advancements, suicide research has continued to move slowly in terms of clinical translation due to the complexity of neural mechanisms, and subjective experiences that seem to underpin this complex human behavior. This paper analyzes the concepts of risk and prevention in the context of suicide in an attempt to bridge the large methodological and theoretical gaps between the biological, psychological, and sociological dimensions. This paper aims to accomplish the following objectives: (1) operationalize the concepts of suicide risk and prevention as they relate to current knowledge and capabilities; (2) synthesize and integrate suicide research across biological, psychological, and sociological dimensions; (3) discuss limitations of each dimension in isolation; (4) suggest a model of etiopathogenesis that incorporates extant literature and bridges unnecessary gaps between dimensions; and (5) suggest future directions for multidimensional research through the inclusion of principles from the physical sciences. Ultimately, this paper provides a basis for a comprehensive model of suicide within a deterministic, chaotic system.

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“…It was estimated that ∼90% of patients with AD exhibit obvious behavioral and psychological symptoms of dementia (BPSD) (Chakraborty et al, 2019), a series of behaviors and neuropsychiatric symptoms such as depression, agitation, mood disorders, sleep disturbances, psychosis, apathy, aberrant motor activity, dysphoria, delusions, and hallucinations in patients with dementia (Dyer et al, 2018). What adds insults to injury, BPSD further seriously affect survival quality of AD patients, leading to huge social burden (Moore et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

Zhang

et al. 2020

Front. Neurosci.

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Alzheimer's disease (AD), the most common cause of dementia, is highly prevalent worldwide with no modifying therapy. Behavioral and psychological symptoms of dementia (BPSD) occur in most patients with AD, and depression is one of the most common AD-related BPSD. Kaixinsan (KXS) is an ancient Chinese herbal prescription widely used to treat dementia and forgetfulness. In this systematic review, we conducted a meta-analysis to assess preclinical evidence for the effects of KXS on cognitive impairment and depression. Thirty-eight articles involving 1,050 animals were included after searching from six databases from the inception up to June 2019. The primary outcome measures were behavioral outcome. Indicators of cognitive function in AD included escape latency, time spent on the target quadrant, and the number of target platform crossings in the Morris water maze (MWM) test. Indicators of depression included number of rearing events and total distance in the open-field test, duration of immobility in the forced swim test, and sucrose consumption or sucrose preference index in the sucrose preference test. The secondary outcomes were mechanisms of KXS for treatment of AD and depression. The results showed that KXS significantly reduced escape latency (P < 0.01), increased time spent in the target quadrant (P < 0.01), and increased the number of target platform crossings (P < 0.01) in the MWM test in AD models compared with control. The possible mechanisms for KXS-mediated improvements in cognitive function were antioxidant activity, anti-inflammatory activity, antiapoptotic activity, neuroprotection, and synapse protection. In addition, the results demonstrated that KXS significantly increased the number of rearing instances (P < 0.01) in the open-field test, decreased the duration of immobility (P < 0.01) in forced swim test, and increased sucrose consumption or sucrose preference index (P < 0.01) in the sucrose preference test in depression models compared with control. The mechanisms of KXS-mediated anti-depressive effects were HPA axis regulation, antioxidant activity, anti-inflammatory activity, synapse protection, and neuroprotection. The results of this study suggested that KXS can be used to effectively treat AD and depression through multiple mechanisms, extrapolating the therapeutic potential of KXS for treating AD-related BPSD.Keywords: Kaixinsan, Alzheimer's disease, behavioral and psychological symptoms of dementia, depression, systematic review, meta-analysis Fu et al. Kaixinsan for AD and Depression

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

Cited by 81 publications

References 149 publications

Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

Etiopathogenesis of Suicide: A Conceptual Analysis of Risk and Prevention Within a Comprehensive, Deterministic Model

Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

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