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Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease
Open accessAbstract
Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.
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“All three studies concur: overactivity and/or aggressiveness were associated with decreased cholinergic markers, particularly in frontal and temporal cortex, and with decreased serotonin and serotonin metabolites.”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Garcia-Alloza et al., 2005
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Metadata
- Authors
- Garcia-Alloza, M., Gil-Bea, F. J., Diez-Ariza, M., Chen, C. P. L.-H., Francis, P. T., Lasheras, B., & Ramirez, M. J.
- Affiliations
- Universidad de Navarra (ES)
- Singapore General Hospital (SG)
- King's College London (GB)
- Venue
- Neuropsychologia
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 43
- Issue
- 3
- Pages
- 442-449
- ISSN
- 0028-3932 (ISSN-L)
- OpenAlex
- W2113839148
- Cited by
- 244
- References
- 52
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 27 · 2023: 12 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 16 · 2015: 6 · 2014: 12 · 2013: 11 · 2012: 11
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neuropsychologia (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, cholinergic system, serotonergic system, acetylcholinesterase, serotonin, aggression, overactivity, psychosis, depression, cognitive impairment, frontal cortex, temporal cortex, postmortem brain
- MeSH terms
- Acetylcholine, Aged, Aged, 80 and over, Aggression, Alzheimer Disease, Cognition Disorders, Depression, Female, Frontal Lobe, Humans, Male, Mental Status Schedule, Psychiatric Status Rating Scales, Psychotic Disorders, Serotonin, Temporal Lobe, Case-Control Studies
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