Possible therapeutic value of melatonin in mild cognitive impairment: A retrospective study
Abstract
Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome characterized by cognitive impairment preceding dementia. Approximately 12% of MCI patients convert to Alzheimer's disease (AD) or other dementia disorders every year. In the present report we retrospectively examined the initial and final neuropsychological assessment of 50 MCI outpatients, 25 of whom had received daily 3-9 mg of a fast-release melatonin preparation p.o. at bedtime for 9-18 months. Melatonin was given in addition to the standard medication prescribed by the attending psychiatrist. Patients treated with melatonin showed significantly better performance in Mini Mental State Examination and the cognitive subscale of the Alzheimer's Disease Assessment Scale. After application of a battery of neuropsychological tests including Mattis' test, Digit-symbol test, Trail A and B tasks and the Rey's verbal test, better performance was found in melatonin-treated patients, except for the Digit-symbol test score which remained unchanged. Abnormally high Beck Depression Inventory scores decreased in melatonin-treated patients, concomitantly with an improvement in wakefulness and sleep quality. The results suggest that melatonin can be a useful add-on drug for treating MCI in a clinical setting.
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A more extensive, longer-term study found that patients with mild cognitive impairment scored better on the Mini-Mental Status Exam and the Sleep Disorders Index when taking melatonin.
“A more extensive, longer-term study found that patients with mild cognitive impairment scored better on the Mini-Mental Status Exam and the Sleep Disorders Index when taking melatonin [106].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [106]
Cites
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980 · see citing works
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
Melatonin : a potent, endogenous hydroxyl radical scavenger
Tan, D. (1993) · Endocrine Journal · Cited by 1,659 · see citing works
Tan, D., Manchester, L. C., Terron, M. P., Flores, L. J., & Reiter, R. J. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00407.x · Cited by 1,601 · see citing works
Amnestic MCI or prodromal Alzheimer's disease?
Dubois, B., & Albert, M. L. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00710-0 · Cited by 543 · see citing works
Evolution of neuronal changes in the course of Alzheimer’s disease
Braak, H., & Braak, E. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6467-9_11 · Cited by 482 · see citing works
A Multicenter, Placebo-controlled Trial of Melatonin for Sleep Disturbance in Alzheimer's Disease
Singer, C., Tractenberg, R. E., Kaye, J., Schafer, K., Gamst, A., Grundman, M., Thomas, R., & Thal, L. J. (2003) · Sleep · doi:10.1093/sleep/26.7.893 · Cited by 407 · see citing works
A4 amyloid protein deposition and the diagnosis of Alzheimer's disease
Davies, L., Wolska, B., Hilbich, C., Multhaup, G., Martins, R. N., Simms, G., Beyreuther, K. T., & Masters, C. L. (1988) · Neurology · doi:10.1212/wnl.38.11.1688 · Cited by 369 · see citing works
The human pineal gland and melatonin in aging and Alzheimer's disease
Wu, Y., & Swaab, D. F. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00196.x · Cited by 368 · see citing works
Liu, R.-Y., Zhou, J.-N., van Heerikhuize, J., Hofman, M. A., & Swaab, D. F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.1.5394 · Cited by 304 · see citing works
Wu, Y., Feenstra, M. G. P., Zhou, J., Liu, R., Toraño, J. S., van Kan, H. J. M., Fischer, D. F., Ravid, R., & Swaab, D. F. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030833 · Cited by 284 · see citing works
Mishima, K., Tozawa, T., Satoh, K., Matsumoto, Y., Hishikawa, Y., & Okawa, M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00510-6 · Cited by 269 · see citing works
Zhou, J., Liu, R., Kamphorst, W., Hofman, M. A., & Swaab, D. F. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00065.x · Cited by 269 · see citing works
Asayama, K., Yamadera, H., Ito, T., Suzuki, H., Kudo, Y., & Endo, S. (2003) · Journal of Nippon Medical School · doi:10.1272/jnms.70.334 · Cited by 242 · see citing works
Pappolla, M. A., Chyan, Y., Pöeggeler, B., Frangione, B., Wilson, G. L., Ghiso, J. A., & Reiter, R. J. (2000) · Journal of Neural Transmission · doi:10.1007/s007020050018 · Cited by 239 · see citing works
Melatonin in Alzheimer's disease and other neurodegenerative disorders
Srinivasan, V. J., Pandi-Perumal, S. R., Cardinali, D. P., Pöeggeler, B., & Hardeland, R. (2006) · Behavioral and Brain Functions · doi:10.1186/1744-9081-2-15 · Cited by 226 · see citing works
Self-citationSkene, D. J., VIVIEN‐ROELS, B., Sparks, D. L., Hunsaker, J. C., Pévet, P., Ravid, D., & Swaab, D. F. (1990) · Brain Research · doi:10.1016/0006-8993(90)90214-v · Cited by 224 · see citing works
Manda, K., Ueno, M., & Anzai, K. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00432.x · Cited by 222 · see citing works
The potential of melatonin in reducing morbidity–mortality after craniocerebral trauma
y Aibar, M. D. M., Murillo-Cabezas, F., Terrón, M. P., Flores, L. J., Tan, D. X., Manchester, L. C., & Reiter, R. J. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00376.x · Cited by 191 · see citing works
The use of melatonin in Alzheimer's disease.
Cardinali, D. P., Brusco, L. I., Liberczuk, C., & Furio, A. M. (2002) · PubMed · Cited by 189 · see citing works
Self-citationMelatonin for treatment of sundowning in elderly persons with dementia – a preliminary study
Cohen‐Mansfield, J., Garfinkel, D., & Lipson, S. (2000) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(00)00068-6 · Cited by 159 · see citing works
Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia
Ferrari, E., Arcaini, A., Gornati, R., Pelanconi, L., Cravello, L., Fioravanti, M., Solerte, S. B., & Magri, F. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00160-1 · Cited by 153 · see citing works
Role of melatonin in Alzheimer-like neurodegeneration
Wang, J.-Z., & Wang, Z.-F. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00260.x · Cited by 150 · see citing works
Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment
Jean‐Louis, G., von Gizycki, H., & Zizi, F. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00557.x · Cited by 143 · see citing works
Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer's disease.
Brusco, L. I., Márquez, M., & Cardinali, D. P. (2000) · PubMed · Cited by 140 · see citing works
Self-citationDaily rhythm of serum melatonin in patients with dementia of the degenerate type
Uchida, K., Okamoto, N., Ohara, K., & Morita, Y. (1996) · Brain Research · doi:10.1016/0006-8993(96)00086-8 · Cited by 138 · see citing works
Ohashi, Y., Okamoto, N., Uchida, K., Iyo, M., Mori, N., & Morita, Y. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00255-8 · Cited by 133 · see citing works
Mishima, K., Okawa, M., Hozumi, S., & Hishikawa, Y. (2000) · Chronobiology International · doi:10.1081/cbi-100101055 · Cited by 108 · see citing works
The Amyloid β Protein Induces Oxidative Damage of Mitochondrial DNA
Bozner, P., Grishko, V. I., LeDoux, S. P., Wilson, G. L., CHYAN, Y.-C., & Pappolla, M. A. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199712000-00010 · Cited by 107 · see citing works
Melatonin Treatment of Day-Night Rhythm Disturbances and Sundowning in Alzheimer Disease
Mahlberg, R., Kunz, D., Sutej, I., Kühl, K.-P., & Hellweg, R. (2004) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000132443.12607.fd · Cited by 96 · see citing works
Pappolla, M. A., Simovich, M. J., Bryant‐Thomas, T., Chyan, Y., Pöeggeler, B., Dubocovich, M. L., Bick, R. J., Perry, G. L., Cruz-Sánchez, F., & Smith, M. A. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.1o838.x · Cited by 91 · see citing works
Effects of melatonin in elderly patients with sleep disturbance: a pilot study
Fainstein, I., Bonetto, A., Brusco, L. I., & Cardinali, D. P. (1997) · Current Therapeutic Research · doi:10.1016/s0011-393x(97)80066-5 · Cited by 88 · see citing works
Self-citationBeneficial effects of melatonin in experimental models of Alzheimer disease1
CHENG, Y., Zheng, F., ZHANG, Q.-Z., & ZHANG, J.-T. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00267.x · Cited by 71 · see citing works
Specificity Clusters of MUC1-Reactive Mouse Monoclonal Antibodies
Hanisch, F. (1998) · Tumor Biology · doi:10.1159/000056511 · Cited by 20 · see citing works
Price (1999) · doi:10.1002/1531-8249(199903)45:3
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Melatonin—A pleiotropic, orchestrating regulator molecule
Hardeland, R., Cardinali, D. P., Srinivasan, V., Spence, D. W., Brown, G. M., & Pandi-Perumal, S. R. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.12.004 · Cited by 843 · see citing works
Self-citationSleep, circadian rhythms, and the pathogenesis of Alzheimer disease
Musiek, E. S., Xiong, D. D., & Holtzman, D. M. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.121 · Cited by 529 · see citing works
Andrade, S., Ramalho, M. J., Loureiro, J. A., & Pereira, M. D. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092313 · Cited by 240 · see citing works
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
“A more extensive, longer-term study found that patients with mild cognitive impairment scored better on the Mini-Mental Status Exam and the Sleep Disorders Index when taking melatonin [107].”
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Hardeland, R. (2012) · The Scientific World Journal · doi:10.1100/2012/640389 · Cited by 173 · see citing works
Melatonin in mitochondrial dysfunction and related disorders
Srinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Brown, G. M., & Cardinali, D. P. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/326320 · Cited by 100 · see citing works
Self-citation
- Authors
- Furio, A. M., Brusco, L. I., & Cardinali, D. P.
- Affiliations
- Universidad de Buenos Aires (AR)
- Corresponding author
- Cardinali, D. P.
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2007-08-28
- Volume
- 43
- Issue
- 4
- Pages
- 404-409
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- OpenAlex
- W1999900894
- Cited by
- 167
- References
- 35
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 7 · 2019: 8 · 2018: 13 · 2017: 8 · 2016: 12 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 11
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pineal Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- melatonin, mild cognitive impairment, Alzheimer's disease, dementia prevention, cognitive function, sleep quality, depression, adjunctive therapy, neuropsychological assessment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Central Nervous System Depressants, Cognition Disorders, Female, Humans, Male, Melatonin, Neuropsychological Tests, Outpatients, Retrospective Studies
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