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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Overactivity and/or aggressiveness in Alzheimer's disease are associated with decreased cholinergic markers, particularly in frontal and temporal cortex, and with decreased serotonin and serotonin metabolites.
“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
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Diagnostic and Statistical Manual of Mental Disorders
&NA; (1988) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198802020-00022 · Cited by 12,603 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859 · see citing works
A rapid radiochemical method for the determination of choline acetyltransferase
Fonnum, F. (1975) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1975.tb11895.x · Cited by 2,358 · see citing works
The cholinergic hypothesis of Alzheimer’s disease: A review of progress
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.66.2.137 · Cited by 2,198 · cited 2× · see citing works
“Reflecting the loss of cholinergic innervation, reductions in AChE and ChAT have been reported in AD brains (Francis et al., 1999; Giacobini, 2003).”
BackgroundRoth, M., Tym, E., Mountjoy, C. Q., Huppert, F. A., Hendrie, H., Verma, S., & Goddard, R. (1986) · British Journal of Psychiatry · doi:10.1192/bjp.149.6.698 · Cited by 2,090 · see citing works
Terry, A. V., & Buccafusco, J. J. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.041616 · Cited by 1,159 · see citing works
Acetylcholine in mind: a neurotransmitter correlate of consciousness?
Perry, E. K., Walker, M. P., Grace, J., & Perry, R. H. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01361-7 · Cited by 764 · see citing works
Role of serotonin in memory impairment.
Buhot, M.-C., Martin, S., & Segu, L. (2000) · Annals of Medicine · doi:10.3109/07853890008998828 · Cited by 419 · see citing works
Danysz, W., & Parsons, C. G. (2003) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.938 · Cited by 404 · see citing works
Mitchell, D. G. V., Colledge, E., Leonard, A., & Blair, J. (2002) · Neuropsychologia · doi:10.1016/s0028-3932(02)00056-8 · Cited by 391 · see citing works
Woodruff, P. W. R., Wright, I. C., Bullmore, E. T., Brammer, M. J., Howard, R. J., Williams, S., Shapleske, J., Rossell, S. L., David, A. S., McGuire, P. K., et al. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.12.1676 · Cited by 331 · see citing works
Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease
Morris, J. C., Cyrus, P. A., Orazem, J. P., Mas, J., Bieber, F., Ruzicka, B. B., & Gulanski, B. (1998) · Neurology · doi:10.1212/wnl.50.5.1222 · Cited by 287 · see citing works
Cholinergic function and Alzheimer's disease
Giacobini, E. (2003) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.935 · Cited by 284 · see citing works
Neuropathologic and Neurochemical Correlates of Psychosis in Primary Dementia
Zubenko, G. S., Moossy, J. J., Martinez, A. J., Rao, G., Claassen, D. O., Rosen, J., & Kopp, U. (1991) · Archives of Neurology · doi:10.1001/archneur.1991.00530180075020 · Cited by 275 · see citing works
Neuropsychiatric aspects of Alzheimer's disease
Cummings, J. L., & Kaufer, D. (1996) · Neurology · doi:10.1212/wnl.47.4.876 · Cited by 252 · see citing works
Glutamatergic systems in Alzheimer's disease
Francis, P. T. (2003) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.934 · Cited by 242 · see citing works
Stern, Y., Albert, M., Brandt, J., Jacobs, D. M., Tang, M.-X., Marder, K. S., Bell, K. L., Sano, M. E. B., Devanand, D. P., Bylsma, F., et al. (1994) · Neurology · doi:10.1212/wnl.44.12.2300 · Cited by 235 · see citing works
Noradrenergic changes, aggressive behavior, and cognition in patients with dementia
Matthews, K. L., Chen, C., Esiri, M. M., Keene, J., Minger, S. L., & Francis, P. T. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01235-5 · Cited by 211 · see citing works
Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients
Štorga-Tomić, D., Vrečko, K., Birkmayer, J. G. D., & Reibnegger, G. J. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(95)12256-7 · Cited by 209 · see citing works
Lewis, D. A. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00393-1 · Cited by 197 · see citing works
Cholinergic deficits contribute to behavioral disturbance in patients with dementia
Minger, S. L., Esiri, M. M., McDonald, B., Keene, J., Carter, J., Hope, T., & Francis, P. T. (2000) · Neurology · doi:10.1212/wnl.55.10.1460 · Cited by 176 · see citing works
Vanderwolf, C. H. (1987) · Behavioural Brain Research · doi:10.1016/0166-4328(87)90241-5 · Cited by 174 · see citing works
Neuropathological Correlates of Psychotic Phenomena in Confirmed Alzheimer's Disease
Förstl, H., Burns, A. S., Levy, R., & Cairns, N. J. (1994) · The British Journal of Psychiatry · doi:10.1192/bjp.165.1.53 · Cited by 161 · see citing works
Role of Serotonin in the Behavioral and Psychological Symptoms of Dementia
Lanctôt, K. L., Herrmann, N., & Mazzotta, P. (2001) · Journal of Neuropsychiatry · doi:10.1176/jnp.13.1.5 · Cited by 153 · see citing works
Garcı́a-Alloza, M., Hirst, W. D., Chen, C., Lasheras, B., Francis, P. T., & Ramírez, M. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300330 · Cited by 151 · see citing works
Gene expression profiling in the post-mortem human brain — no cause for dismay
Bahn, S., Augood, S. J., Ryan, M., Standaert, D. G., Starkey, M., & Emson, P. C. (2001) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(01)00099-0 · Cited by 146 · see citing works
Chen, C., Alder, J. T., Bowen, D. M., Esiri, M. M., McDonald, B., Hope, T., Jobst, K. A., & Francis, P. T. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66041592.x · Cited by 136 · see citing works
Chen, C., Eastwood, S., Hope, T., Mcdonald, B., Francis, P., & Esiri, M. (2000) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2000.00254.x · Cited by 124 · see citing works
Neuropsychiatric Symptoms and Cholinergic Therapy for Alzheimer’s Disease
Levy, M. L., Cummings, J. L., & Kahn-Rose, R. (1999) · Gerontology · doi:10.1159/000052760 · Cited by 121 · see citing works
Psychosis of Alzheimer’s disease is associated with elevated muscarinic M 2 binding in the cortex
Lai, M. K. P., Lai, O. –., Keene, J., Esiri, M. M., Francis, P. T., Hope, T., & Chen, C. (2001) · Neurology · doi:10.1212/wnl.57.5.805 · Cited by 114 · see citing works
Hope, T., & Fairburn, C. G. (1992) · Psychological Medicine · doi:10.1017/s0033291700032888 · Cited by 107 · see citing works
Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation
Halliday, G. M., McCann, H., Pamphlett, R., Brooks, W. S., Creasey, H. M., McCusker, E. A., Cotton, R. G. H., Broe, G. A., & Harper, C. (1992) · Acta Neuropathologica · doi:10.1007/bf00227741 · Cited by 104 · see citing works
Pérez‐Otaño, I., Herrero, M. T., Oset, C., CEBALLOS, M. L. D., Luquín, M. R., Obeso, J. A., & del Rı́o, J. A. (1991) · Brain Research · doi:10.1016/0006-8993(91)91444-6 · Cited by 98 · see citing works
Antipsychotic Medications and the Elderly
Byerly, M., Weber, M., Brooks, D. L., Snow, L. R., Worley, M. A., & Lescouflair, E. (2001) · Drugs & Aging · doi:10.2165/00002512-200118010-00004 · Cited by 98 · see citing works
Porter, R., Lunn, B. S., & O'Brien, J. T. (2002) · Psychological Medicine · doi:10.1017/s0033291702006906 · Cited by 89 · see citing works
Postmortem serotoninergic correlates of cognitive decline in Alzheimer??s disease
Lai, M. K. P., Tsang, S. W. Y., Francis, P. T., Keene, J., Hope, T., Esiri, M. M., Spence, I., & Chen, C. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00021 · Cited by 86 · see citing works
Is paradoxical pharmacology a strategy worth pursuing?
Bond, R. A. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01711-9 · Cited by 73 · see citing works
Effects of bis(7)-tacrine, a novel anti-Alzheimerʼs agent, on rat brain AChE
Wang, H., Carlier, P. R., Ho, W. L., Wu, D., Lee, N. T. K., Li, C. P. L., Pang, Y., & Han, Y. (1999) · Neuroreport · doi:10.1097/00001756-199903170-00023 · Cited by 60 · see citing works
New Focus on Behavioral and Psychological Signs and Symptoms of Dementia
Finkel, S. I. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297003360 · Cited by 59 · see citing works
Donepezil for the Treatment of Behavioral Symptoms in Patients With Alzheimer's Disease
Paleacu, D., Mazeh, D., Mirecki, I., Even, M., & Barak, Y. (2002) · Clinical Neuropharmacology · doi:10.1097/00002826-200211000-00007 · Cited by 53 · see citing works
Measuring cognition in advanced Alzheimer’s disease for clinical trials
Schmitt, F. A., Locke, D. E. C., Ashford, J. W., Reisberg, ., Ferris, S. H., Möbius, H. J., & Stöffler, A. (2002) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6139-5_14 · Cited by 44 · see citing works
Magai, C., Cohen, C. I., Culver, C., Gomberg, D., & Malatesta, C. (1997) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(199711)12:11 · Cited by 41 · see citing works
Dringenberg, H. C., & Zalan, R. M. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01669-8 · Cited by 37 · see citing works
Pharmacological treatment of non-cognitive disturbances in dementia disorders
Parnetti, L., Amici, S., Lanari, A., & Gallai, V. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00316-5 · Cited by 36 · see citing works
Antipsychotic Agents in Patients with Dementia
Defilippi, J. L., & Crismon, M. L. (2000) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.20.1.23.34661 · Cited by 30 · see citing works
Maintaining Cognitive Function in Alzheimer Disease
Tariot, P. N. (2001) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200108001-00005 · Cited by 27 · see citing works
Takahashi, A., Ishimaru, H., Ikarashi, Y., Kishi, E., & Maruyama, Y. (1997) · Brain Research Protocols · doi:10.1016/s1385-299x(96)00013-x · Cited by 9 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits?
Rosenberg, P. B., Nowrangi, M. A., & Lyketsos, C. G. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.05.005 · Cited by 302 · see citing works
Monoaminergic neuropathology in Alzheimer’s disease
Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Milošević, N. J., Bažadona, D., Buée, L., de Silva, R., Giovanni, G. D., et al. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.001 · Cited by 289 · see citing works
The serotonergic system and cognitive function
Štrac, D. Š., Pivac, N., & Mück‐Šeler, D. (2016) · Translational Neuroscience · doi:10.1515/tnsci-2016-0007 · Cited by 282 · see citing works
The serotonergic system in ageing and Alzheimer's disease
Rodriguez, J. J., Noristani, H. N., & Verkhratsky, A. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.06.010 · Cited by 266 · see citing works
Chen, Y., Dang, M., & Zhang, Z. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00456-1 · Cited by 224 · see citing works
Bolea, I., Juárez‐Jiménez, J., Rı́os, C. D. L., Chioua, M., Pouplana, R., Luque, F. J., Unzeta, M., Marco, J. L., & Samadi, A. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200853t · Cited by 220 · see citing works
Psychosis in Alzheimer’s Disease
Murray, P. S., Kumar, S., DeMichele‐Sweet, M. A. A., & Sweet, R. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.020 · Cited by 198 · see citing works
Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer's disease
Lanari, A., Amenta, F., Silvestrelli, G., Tomassoni, D., & Parnetti, L. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.016 · Cited by 180 · see citing works
Beyond the Cholinergic Hypothesis: Do Current Drugs Work in Alzheimer's Disease?
Martorana, A., Esposito, Z., & Koch, G. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00175.x · Cited by 174 · see citing works
Wang, H., Liang, S., Burgdorf, J. S., Wess, J., & Yeomans, J. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001893 · Cited by 172 · see citing works
O'Hara, R., Schröder, C. M., Mahadevan, R., Schatzberg, A. F., Lindley, S., Fox, S., Weiner, M., Kraemer, H. C., Noda, A., Lin, X., et al. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001978 · Cited by 171 · see citing works
Xu, J., Begley, P., Church, S. J., Patassini, S., Hollywood, K. A., Jüllig, M., Curtis, M. A., Waldvogel, H. J., Faull, R. L. M., Unwin, R. D., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.03.001 · Cited by 163 · see citing works
5‐HT radioligands for human brain imaging with PET and SPECT
Paterson, L. M., Kornum, B. R., Nutt, D., Pike, V. W., & Knudsen, G. M. (2011) · Medicinal Research Reviews · doi:10.1002/med.20245 · Cited by 150 · see citing works
Reconsideration of Anticholinesterase Therapeutic Strategies against Alzheimer’s Disease
Wang, H., & Zhang, H. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00391 · Cited by 140 · see citing works
Kumar, B., Sheetal, S., Mantha, A. K., & Kumar, V. (2016) · RSC Advances · doi:10.1039/c6ra00302h · Cited by 138 · see citing works
Meneses, A., & Perez-Garcia, G. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.02.001 · Cited by 130 · see citing works
Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia
Nowrangi, M. A., Lyketsos, C. G., & Rosenberg, P. B. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0096-3 · Cited by 129 · see citing works
Haider, S., Liaquat, L., Ahmad, S., Batool, Z., Siddiqui, R. A., Tabassum, S., Shahzad, S., Rafiq, S., & Naz, N. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227631 · Cited by 127 · see citing works
Whiley, L., Chappell, K. E., D’Hondt, E., Lewis, M. R., Jiménez, B., Snowden, S. G., Soininen, H. S., Kłoszewska, I., Mecocci, P., Tsolaki, M., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00741-z · Cited by 123 · see citing works
Joubert, J., Foka, G. B., Repsold, B. P., Oliver, D. W., Kapp, E., & Malan, S. F. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.09.041 · Cited by 123 · see citing works
Serotonergic system, cognition, and BPSD in Alzheimer’s disease
Chakraborty, S., Lennon, J. C., Malkaram, S. A., Zeng, Y., Fisher, D. W., & Dong, H. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.03.050 · Cited by 123 · see citing works
Cholinergic system function and cognition in mild cognitive impairment
Haense, C., Kalbe, E., Herholz, K., Hohmann, C., Neumaier, B., Krais, R., & Heiss, W. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.08.015 · Cited by 121 · see citing works
Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients
Lorke, D. E., Lü, G., Cho, E. Y. P., & Yew, D. T. W. (2006) · BMC Neuroscience · doi:10.1186/1471-2202-7-36 · Cited by 113 · see citing works
Pinto, T., Lanctôt, K. L., & Herrmann, N. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.01.003 · Cited by 106 · see citing works
Neurochemical basis for symptomatic treatment of Alzheimer's disease
Francis, P. T., Ramírez, M. J., & Lai, M. K. P. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.02.010 · Cited by 104 · see citing works
Egashira, N., Iwasaki, K., Ishibashi, A., Hayakawa, K., Okuno, R., Abe, M., Uchida, N., Mishima, K., Takasaki, K., Nishimura, R., et al. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.05.010 · Cited by 103 · see citing works
VRX-03011, a novel 5-HT4 agonist, enhances memory and hippocampal acetylcholine efflux
Mohler, E. G., Shacham, S., Noiman, S., Lezoualc’h, F., Robert, S. J., Gastineau, M., Rutkowski, J., Marantz, Y., Dumuis, A., Bockaert, J., et al. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.016 · Cited by 98 · see citing works
Engelborghs, S., Vloeberghs, E., Bastard, N. L., Buggenhout, M. V., Mariën, P., Somers, N., Nagels, G., Pickut, B. A., & Deyn, P. P. D. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.10.018 · Cited by 95 · see citing works
Aznar, S., & Knudsen, G. M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100390 · Cited by 93 · see citing works
Serotonergic Therapies for Cognitive Symptoms in Alzheimer’s Disease: Rationale and Current Status
Ramírez, M. J., Lai, M. K. P., Tordera, R. M., & Francis, P. T. (2014) · Drugs · doi:10.1007/s40265-014-0217-5 · Cited by 92 · see citing works
Kumar, B., Dwivedi, A. R., Sarkar, B., Gupta, S. K., Krishnamurthy, S., Mantha, A. K., Parkash, J., & Kumar, V. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00220 · Cited by 92 · see citing works
Chan, A., Tchantchou, F., Graves, V., Rozen, R., & Shea, T. B. (2008) · The Journal of Nutrition, Health & Aging · doi:10.1007/bf02982630 · Cited by 86 · see citing works
Serotonin: modulator of a drive to withdraw.
Tops, M., Russo, S., Boksem, M. A. S., & Tucker, D. M. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.03.009 · Cited by 86 · see citing works
NMDA Neurotransmission Dysfunction in Behavioral and Psychological Symptoms of Alzheimer's Disease
Huang, Y.-J., Lin, C., Lane, H., & Tsaid, G. E. (2012) · Current Neuropharmacology · doi:10.2174/157015912803217288 · Cited by 85 · see citing works
Sambeth, A., Blokland, A., Harmer, C. J., Kilkens, T. O. C., Nathan, P. J., Porter, R., Schmitt, J. A. J., Scholtissen, B., Sobczak, S., Young, A. H., et al. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.11.009 · Cited by 83 · see citing works
Behavioral and Psychiatric Symptoms of Dementia and Rate of Decline in Alzheimer’s Disease
Gottesman, R. T., & Stern, Y. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01062 · Cited by 80 · see citing works
Involvement of the GABAergic system in depressive symptoms of Alzheimer's disease
Garcı́a-Alloza, M., Tsang, S. W. Y., Gil-Bea, F. J., Francis, P. T., Lai, M. K. P., Marcos, B., Chen, C., & Ramírez, M. J. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.06.003 · Cited by 77 · see citing works
Aging-associated sensory decline and Alzheimer’s disease
Hong, S., Baek, S.-H., Lai, M. K. P., Arumugam, T. V., & Jo, D.-G. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00776-y · Cited by 76 · see citing works
Geldenhuys, W. J., & der Schyf, C. J. V. (2009) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.51 · Cited by 73 · see citing works
Samadi, A., Chioua, M., Bolea, I., Rı́os, C. D. L., Iriepa, I., Moraleda, I., Bastida, Á., Esteban, G., Unzeta, M., Galvez‐Ruano, E., et al. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.05.048 · Cited by 70 · see citing works
d’Angremont, E., Begemann, M. J. H., van Laar, T., & Sommer, I. E. C. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.1835 · Cited by 71 · see citing works
Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases
Giovanni, G. D., Štrac, D. Š., Solé, M., Unzeta, M., Tipton, K. F., Mück‐Šeler, D., Bolea, I., Corte, L., Perković, M. N., Pivac, N., et al. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00541 · Cited by 71 · see citing works
Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials.
Mortby, M., Adler, L., Agüera-Ortiz, L., Bateman, D., Brodaty, H., Cantillon, M., Geda, Y., Ismail, Z., Lanctôt, K., Marshall, G., et al. (2021) · The American journal of geriatric psychiatry · doi:10.1016/j.jagp.2021.06.016 · Cited by 55 · see citing works
Hallucinations in Neurodegenerative Diseases
Burghaus, L., Eggers, C., Timmermann, L., Fink, G. R., & Diederich, N. J. (2011) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2011.00247.x · Cited by 65 · see citing works
Dam, D. V., Vermeiren, Y., Dekker, A. D., Naudé, P. J. W., & Deyn, P. P. D. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160502123607 · Cited by 65 · see citing works
Non-pharmacological Management of Behavioral Symptoms in Frontotemporal and Other Dementias
Barton, C., Ketelle, R., Merrilees, J. J., & Miller, B. L. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0618-1 · Cited by 66 · see citing works
Meneses, A., Perez-Garcia, G., Liy-Salmerón, G., Flores-Galvez, D., Castillo, C., & Castillo, E. F. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.11.023 · Cited by 64 · see citing works
Weissberger, G. H., Melrose, R. J., Narvaez, T. A., Harwood, D. G., Mandelkern, M. A., & Sultzer, D. L. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.01.017 · Cited by 63 · see citing works
Huang, L., Abuhamdah, S. M. A., Howes, M. R., Dixon, C. L., Elliot, M. S. J., Ballard, C. G., Holmes, C., Burns, A. S., Perry, E. K., Francis, P. T., et al. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp/60.11.0013 · Cited by 63 · see citing works
Chaudhary, S., Zhornitsky, S., Chao, H. H., van Dyck, C. H., & Li, C.-S. R. (2022) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/15333175221082834 · Cited by 61 · see citing works
Neumann, S. A., Brown, S. M., Ferrell, R. E., Flory, J. D., Manuck, S. B., & Hariri, A. R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.059 · Cited by 61 · see citing works
Scuteri, D., Rombolà, L., Morrone, L. A., Bagetta, G., Sakurada, S., Sakurada, T., Tonin, P., & Corasaniti, M. T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133327 · Cited by 60 · see citing works
Psychosis in Alzheimer’s Disease
Ballard, C. G., Kales, H. C., Lyketsos, C. G., Aarsland, D., Creese, B., Mills, R., Williams, H., & Sweet, R. A. (2020) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-020-01074-y · Cited by 59 · see citing works
Shea, T. B. (2007) · Neuromolecular medicine · doi:10.1007/s12017-007-8005-y · Cited by 59 · see citing works
Mück‐Šeler, D., Presečki, P., Mimica, N., Mustapić, M., Pivac, N., Perhoč, A. B., Erjavec, G. N., & Folnegović-Šmalc, V. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.07.004 · Cited by 58 · see citing works
Laursen, B., Mørk, A., Plath, N., Kristiansen, U., & Bastlund, J. F. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.012 · Cited by 58 · see citing works
Ciullo, V., Spalletta, G., Caltagirone, C., Banaj, N., Vecchio, D., Piras, F., & Piras, F. (2020) · The Neuroscientist · doi:10.1177/1073858420936167 · Cited by 58 · see citing works
Vermeiren, Y., Le Bastard, N., Van Hemelrijck, A., Drinkenburg, W. H., Engelborghs, S., & De Deyn, P. P. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.06.010 · Cited by 56 · see citing works
The Role of Serotonin Receptors in Alzheimer’s disease
Butzlaff, M., & Ponimaskin, E. G. (2016) · Russian Agency for Digital Standardization · doi:10.20388/omp2016.001.0018 · Cited by 56 · see citing works
Metabolic disorder in Alzheimer’s disease
Poddar, M. K., Banerjee, S., Chakraborty, A., & Dutta, D. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00673-z · Cited by 55 · see citing works
Mitchell, E. S., Hoplight, B. J., Lear, S. P., & Neumaier, J. F. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.10.002 · Cited by 54 · see citing works
Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease
Kumar, R., Kumar, V., Kumar, B., Thakur, A., & Dwivedi, A. R. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210512005508 · Cited by 54 · see citing works
The neurochemistry of agitation in Alzheimer’s disease: a systematic review
Liu, K. Y., Stringer, A., Reeves, S., & Howard, R. J. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.03.003 · Cited by 54 · see citing works
Neurotransmitter measures in the cerebrospinal fluid of patients with Alzheimer's disease: a review.
Štrac, D. Š., Mück‐Šeler, D., & Pivac, N. (2015) · PubMed · Cited by 51 · see citing works
Abuhamdah, S. M. A., Huang, L., Elliott, M. S. J., Howes, M. R., Ballard, C. G., Holmes, C., Burns, A. S., Perry, E. K., Francis, P. T., Lees, G., et al. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.3.0014 · Cited by 52 · see citing works
Hiroi, R., Weyrich, G., Koebele, S. V., Mennenga, S., Talboom, J., Hewitt, L. T., Lavery, C. N., Mendoza, P., Jordan, A., & Bimonte-Nelson, H. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00517 · Cited by 50 · see citing works
Citalopram for agitation in Alzheimer's disease: Design and methods
Drye, L. T., Ismail, Z., Porsteinsson, A. P., Rosenberg, P. B., Weintraub, D. A., Marano, C. M., Pelton, G. H., Frangakis, C., Rabins, P. V., Munro, C. A., et al. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.01.007 · Cited by 50 · see citing works
Behavioral and neuropsychiatric disorders in Alzheimer's disease
Cortés, N., Andrade, V., & Maccioni, R. B. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180005 · Cited by 57 · see citing works
Ehrhardt, S., Porsteinsson, A. P., Munro, C. A., Rosenberg, P. B., Pollock, B. G., Devanand, D. P., Mintzer, J. E., Rajji, T. K., Ismail, Z., Schneider, L. S. S., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.4946 · Cited by 48 · see citing works
Jha, S. K., Jha, N. K., Kumar, D., Sharma, R., Shrivastava, A., Ambasta, R. K., & Kumar, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160623 · Cited by 46 · see citing works
Use of Yokukansan (TJ‐54) in the treatment of neurological disorders: a review
de Caires, S., & Steenkamp, V. (2010) · Phytotherapy Research · doi:10.1002/ptr.3146 · Cited by 45 · see citing works
Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present)
Wang, N., Qiu, P., Cui, W., Yan, X., Zhang, B., & He, S. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867326666181203124102 · Cited by 45 · see citing works
Zhou, C., Chao, F., Zhang, Y., Jiang, L. H., Zhang, L., Fan, J., Wu, Y., Dou, X., & Tang, Y. C. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24616 · Cited by 44 · see citing works
Mechanistic complexities of bone loss in Alzheimer’s disease: a review
Frame, G., Bretland, K. A., & Dengler-Crish, C. M. (2020) · Connective Tissue Research · doi:10.1080/03008207.2019.1624734 · Cited by 44 · see citing works
Pharmacological interventions for apathy in Alzheimer's disease
Ruthirakuhan, M. T., Herrmann, N., Abraham, E. H., Chan, S., & Lanctôt, K. L. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012197.pub2 · Cited by 113 · see citing works
Behavioral effects and ChE measures after acute and repeated administration of malathion in rats
Assini, F. L., Zanette, K. D., Brocardo, P. S., Pandolfo, P., Rodrigues, A. L. S., & Takahashi, R. N. (2005) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2005.05.007 · Cited by 43 · see citing works
The role of nicotinic cholinergic neurotransmission in delusional thinking
Caton, M., Ochoa, E. L. M., & Barrantes, F. J. (2020) · Schizophrenia · doi:10.1038/s41537-020-0105-9 · Cited by 43 · see citing works
Serotonin modulation of hippocampal functions: From anatomy to neurotherapeutics
Bombardi, C., Grandis, A., Pivac, N., Šagud, M., Lucas, G., Chagraoui, A., Lemaire, V., Deurwaerdère, P. D., & Giovanni, G. D. (2021) · Progress in brain research · doi:10.1016/bs.pbr.2021.01.031 · Cited by 41 · see citing works
Noristani, H. N., Olabarria, M., Verkhratsky, A., & Rodriguez, J. J. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07274.x · Cited by 41 · see citing works
Dauwan, M., Linszen, M. M. J., Lemstra, A. W., Scheltens, P., Stam, C. J., & Sommer, I. E. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.03.013 · Cited by 37 · see citing works
El‐Khadragy, M. F., Al-Olayan, E. M., & Moneim, A. E. A. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140618105404 · Cited by 40 · see citing works
Borroni, B., Grassi, M., Agosti, C., Archetti, S., Costanzi, C., Cornali, C., Caltagirone, C., Caimi, L., Luca, M. D., & Padovani, A. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000192491.50802.c3 · Cited by 40 · see citing works
Acker, C. I., Luchese, C., Prigol, M., & Nogueira, C. W. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.03.069 · Cited by 39 · see citing works
Carson, R., Craig, D., Hart, D. J., Todd, S., McGuinness, B., Johnston, J. A., O’Neill, F. A., Ritchie, C. W., & Passmore, A. P. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8048-8 · Cited by 38 · see citing works
Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease
Smith, G. S., Kramer, E., Ma, Y., Hermann, C. R., DHAWAN, V. M., Chaly, T., & Eidelberg, D. (2009) · Brain · doi:10.1093/brain/awn326 · Cited by 38 · see citing works
Lemon Balm and Lavender herbal essential oils: Old and new ways to treat emotional disorders?
Abuhamdah, S. M. A., & Chazot, P. L. (2008) · Current Anaesthesia and Critical Care · doi:10.1016/j.cacc.2008.05.005 · Cited by 38 · see citing works
Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease
Hirao, K., Pontone, G. M., & Smith, G. S. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.010 · Cited by 37 · see citing works
Olesen, L. Ø., Bouzinova, E. V., Severino, M., Sivasaravanaparan, M., Hasselstrøm, J. B., Finsen, B. R., & Wiborg, O. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165144 · Cited by 37 · see citing works
Noristani, H. N., Meadows, R. S., Olabarria, M., Verkhratsky, A., & Rodríguez, J. J. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.79 · Cited by 36 · see citing works
Kinetics of serotonin oxidation by heme–Aβ relevant to Alzheimer’s disease
Mukherjee, S., Seal, M., & Dey, S. G. (2014) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-014-1193-7 · Cited by 35 · see citing works
Synergistic inhibition of butyrylcholinesterase by galantamine and citalopram
Walsh, R., Rockwood, K. J., Martin, E. V., & Darvesh, S. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.010 · Cited by 35 · see citing works
Pharmacological Therapy for Apathy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Sepehry, A. A., Sarai, M., & Hsiung, G. R. (2017) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2016.426 · Cited by 35 · see citing works
Dementia-related psychosis and the potential role for pimavanserin
Cummings, J. L., Devanand, D. P., & Stahl, S. M. (2020) · CNS Spectrums · doi:10.1017/s1092852920001765 · Cited by 35 · see citing works
Garcı́a-Alloza, M., Zaldua, N., Diez-Ariza, M., Marcos, B., Lasheras, B., Gil-Bea, F. J., & Ramírez, M. J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240469.20167.89 · Cited by 36 · see citing works
Paesler, K., Xie, K., Hettich, M. M., Siwek, M. E., Ryan, D. P., Schröder, S., Papazoglou, A., Broich, K., Müller, R., Trog, A., et al. (2015) · Neural Plasticity · doi:10.1155/2015/825157 · Cited by 36 · see citing works
The neural basis of neuropsychiatric symptoms in Alzheimer’s disease
Zhang, N. K., Zhang, S. K., Zhang, L. I., Tao, H. W., & Zhang, G. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1487875 · Cited by 35 · see citing works
Increased Levels of Brain Adrenomedullin in the Neuropathology of Alzheimer’s Disease
Ferrero, H., Larráyoz, I. M., Martišová, E., Solas, M., Howlett, D. R., Francis, P. T., Gil-Bea, F. J., Martı́nez, A., & Ramírez, M. J. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0700-6 · Cited by 34 · see citing works
Current and Emerging Pharmacological Targets for the Treatment of Alzheimer’s Disease
Morsy, A., & Trippier, P. C. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190744 · Cited by 34 · see citing works
Cazzola, R., Rondanelli, M., Faliva, M. A., & Cestaro, B. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.09.004 · Cited by 34 · see citing works
Emerging treatments for the behavioral and psychological symptoms of dementia
Anand, A., Khurana, P., Chawla, J. S., Sharma, N., & Khurana, N. (2017) · CNS Spectrums · doi:10.1017/s1092852917000530 · Cited by 34 · see citing works
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
