Behavioral and neuropsychiatric disorders in Alzheimer's disease
Open accessAbstract
Alzheimer's disease (AD) is the most frequent type of dementia in the elderly, severely affecting functional and executive skills of subjects suffering from this disease. Moreover, the distress of caregivers as well as the social implications constitute a critical issue for families. Furthermore, cognitive impairment, along with behavioral disorders and neuropsychiatric symptoms are characteristics of AD. Although these are present with variations in prevalence, intensity, and progression, an important core of them is visible before cognitive impairment, especially depression and apathy, which affect at least 50% of patients. The most updated literature shows that depression and/or behavioral and neuropsychiatric symptoms (BNS) are part of the initial phase of the disease rather than just a risk factor. Thus, mood disorders are associated with anomalies in specific brain regions that disturb the normal balance of neurotransmission. This in turn is linked with an inflammatory pathway that leads to microglial activation and aggregated neurofibrillary tangle formation, finally triggering neuronal loss, according to our neuroimmunomodulation theory. Altogether, inflammation and tau aggregation are observed in preclinical stages, preceding the BNS of patients, which in turn are exhibited earlier than cognitive and functional impairment detected in AD. This review is focused on the latest insights of cellular and molecular processes associated with BNS in asymptomatic early-onset s…
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Neuropsychiatric symptoms, alongside behavioral disorders, deficits in locomotor activity, and changes in reflex and sensory function, precede cognitive deficits in AD.
“Moreover, neuropsychiatric symptoms, alongside behavioral disorders, deficits in locomotor activity, and changes in reflex and sensory function, precede cognitive deficits in AD (Albers et al., 2015; Buchman and Bennett, 2011; Cortes et al., 2018).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Cortes et al., 2018
Cites
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983 · see citing works
Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925 · see citing works
The brain reward circuitry in mood disorders
Russo, S. J., & Nestler, E. J. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3381 · Cited by 1,870 · see citing works
Behavioral and psychological symptoms of dementia
Cerejeira, J., Lagarto, L., & Mukaetova-Ladinska, E. B. (2012) · Frontiers in Neurology · doi:10.3389/fneur.2012.00073 · Cited by 1,425 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Zhao, Q.-F., Tan, L., Wang, H.-F., Jiang, T., Tan, M.-S., Tan, L., Xu, W., Li, J.-Q., Wang, J., Lai, T.-J., et al. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.09.069 · Cited by 916 · see citing works
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · see citing works
Hamelin, L., Lagarde, J., Dorothée, G., Leroy, C., Labit, M., Comley, R. A., de Souza, L. C., Corne, H., Dauphinot, L., Bertoux, M., et al. (2016) · Brain · doi:10.1093/brain/aww017 · Cited by 519 · see citing works
Nobili, A., Latagliata, E. C., Viscomi, M. T., Cavallucci, V., Cutuli, D., Giacovazzo, G., Krashia, P., Rizzo, F. R., Marino, R., Federici, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms14727 · Cited by 514 · cited 1× · see citing works
“In addi374 tion, it has been recently determined that the loss of 375 dopamine affects memory dysfunction in a transgenic 376 mouse of AD [111].”
Morales, I., Guzmán-MartÃnez, L., Cerda-Troncoso, C., FarÃas, G. A., & Maccioni, R. B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00112 · Cited by 490 · see citing works
Self-citationThe molecular bases of Alzheimer’s disease and other neurodegenerative disorders
Maccioni, R. B., Muñoz, J. P., & Barbeito, L. (2001) · Archives of Medical Research · doi:10.1016/s0188-4409(01)00316-2 · Cited by 474 · see citing works
Neuroinflammation: Implications for the Pathogenesis and Molecular Diagnosis of Alzheimer's Disease
Rojo, L. E., Fernández, J. A., Maccioni, A. A., Jimenez, J. M., & Maccioni, R. B. (2008) · Archives of Medical Research · doi:10.1016/j.arcmed.2007.10.001 · Cited by 351 · see citing works
Self-citationCole, J., Costafreda, S. G., McGuffin, P., & Fu, C. H. Y. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.05.057 · Cited by 319 · see citing works
Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease
Villegas-Llerena, C., Phillips, A., Garcia-Reitboeck, P., Hardy, J., & Pocock, J. M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.004 · Cited by 270 · see citing works
Tschanz, J. T., Corcoran, C. D., Schwartz, S., Treiber, K., Green, R. C., Norton, M. C., Mielke, M. M., Piercy, K., Steinberg, M., Rabins, P. V., et al. (2011) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181faec23 · Cited by 244 · cited 4× · see citing works
“TheintensityofBNSincreasedoverthetime,how-everthesearevariableandepisodic[22],andBNS havebeendirectlyassociatedwithadiminishingin survivalrates[63].”
InfluentialGarcia-Alloza, M., Gil-Bea, F. J., Diez-Ariza, M., Chen, C. P. L.-H., Francis, P. T., Lasheras, B., & Ramirez, M. J. (2005) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2004.06.007 · Cited by 244 · see citing works
Dose-dependent effects of endotoxin on neurobehavioral functions in humans
Grigoleit, J.-S., Kullmann, J. S., Wolf, O. T., Hammes, F., Wegner, A., Jablonowski, S., Engler, H., Gizewski, E., Oberbeck, R., & Schedlowski, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028330 · Cited by 241 · see citing works
Neuroimmunomodulation in the Pathogenesis of Alzheimer’s Disease
Morales, I., Farías, G., & Maccioni, R. B. (2010) · Neuroimmunomodulation · doi:10.1159/000258724 · Cited by 162 · see citing works
Self-citationKetamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression
Lener, M. S., Kadriu, B., & Zarate, C. A. (2017) · Drugs · doi:10.1007/s40265-017-0702-8 · Cited by 131 · see citing works
Neuropsychiatric correlates of cerebrospinal fluid biomarkers in Alzheimer's disease
Skogseth, R., Mulugeta, E., Ballard, C., Rongve, A., Nore, S., Alves, G., & Aarsland, D. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000137671 · Cited by 71 · see citing works
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The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?
Megur, A., Baltriukienė, D., Bukelskienė, V., & Burokas, A. (2020) · Nutrients · doi:10.3390/nu13010037 · Cited by 323 · see citing works
Fongsaran, C., Jirakanwisal, K., Peng, B.-H., Fracassi, A., Taglialatela, G., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2024.100780 · Cited by 9 · see citing works
- Authors
- Cortés, N., Andrade, V., & Maccioni, R. B.
- Affiliations
- University of Chile (CL)
- Corresponding author
- Maccioni, Ricardo B.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2018-05-08
- Volume
- 63
- Issue
- 3
- Pages
- 899-910
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2802693162
- Cited by
- 57
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 12 · 2023: 3 · 2022: 10 · 2021: 11 · 2020: 10 · 2019: 4 · 2018: 2
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease
- MeSH terms
- Affect, Alzheimer Disease, Mental Disorders, Encephalitis, Humans, Neuropsychological Tests, Psychiatric Status Rating Scales, Microglia
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