{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:18:39Z","timestamp":1789683519759,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: Mild cognitive impairment (MCI) is characterized by cognition impairment that does not interfere with the usual activities of daily living. It is considered to be a transitional stage between normal aging and dementia. No treatment is available for MCI. Methods: This retrospective cohort study included 55 patients (29 males and 26 females, aged 56\u201375 years) with a diagnosis of amnestic MCI who attended the Center for Cognitive Disorder and Dementia of the IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy) between January and December of 2017. As we aimed to evaluate the effect of cocoa polyphenols on cognition, the study population was separated into two groups depending on the change in their Mini-Mental State Examination (MMSE) score at a one-year follow-up. Results: Compared to G2 (i.e., patients with a worsening in cognitive functions), the rate of polyphenol intake was significantly higher in patients without a worsening in cognition (i.e., G1) (\u03c72 = 13.79, df = 1, p-value &lt; 0.001). By subdividing G1 patients based on whether they improved or were stable at follow-up, we found that 46.2% of those who had improved were treated with polyphenols. Conclusions: Dietary supplementation of cocoa flavonoids seems to reduce the progression of MCI to dementia. Further prospective studies with larger sample volumes are required to confirm these promising findings.<\/jats:p>","DOI":"10.3390\/medicina55050156","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T11:06:46Z","timestamp":1558091206000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Efficacy of Cocoa Polyphenols in the Treatment of Mild Cognitive Impairment: A Retrospective Study"],"prefix":"10.3390","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-3166","authenticated-orcid":false,"given":"Rocco Salvatore","family":"Calabr\u00f2","sequence":"first","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7509-3833","authenticated-orcid":false,"given":"Maria Cristina","family":"De Cola","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-645X","authenticated-orcid":false,"given":"Giuseppe","family":"Gervasi","sequence":"additional","affiliation":[{"name":"Hygiene and Preventive Medicine School, Department of Biomedicine and Prevention, University of Rome, Tor Vergata, 00133 Rome, Italy"},{"name":"National Center for Disease Prevention and Health Promotion, National Institute of Health, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Portaro","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Naro","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Accorinti","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Manuli","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Marra","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Placido","family":"Bramanti","sequence":"additional","affiliation":[{"name":"Behavioral and Robotic Neurorehab Unit, IRCCS Centro Neurolesi \u201cBonino Pulejo\u201d, 98123 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S1474-4422(03)00262-X","article-title":"Mild cognitive impairment: Prevalence, prognosis, aetiology, and treatment","volume":"2","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2147\/CIA.S73922","article-title":"Mild cognitive impairment and its management in older people","volume":"10","author":"Eshkoor","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1212\/CPJ.0000000000000576","article-title":"Shared decision making in mildcognitive impairment","volume":"9","author":"Mejia","year":"2019","journal-title":"Neurol. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1177\/1533317518791401","article-title":"Mild Cognitive Impairment in Clinical Practice: A Review Article","volume":"33","author":"Jongsiriyanyong","year":"2018","journal-title":"Am. J. Alzheimers Dis. Other Demen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1212\/WNL.41.7.1006","article-title":"Mild cognitive impairment in the elderly: Predictors of dementia","volume":"41","author":"Flicker","year":"1991","journal-title":"Neurology"},{"key":"ref_6","first-page":"S44","article-title":"Mild cognitive impairment: The dilemma","volume":"5","author":"Pinto","year":"2009","journal-title":"Indian J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1001\/archneur.56.3.303","article-title":"Mild cognitive impairment: Clinical characterization and outcome","volume":"56","author":"Petersen","year":"1999","journal-title":"Arch. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/2046-4053-1-25","article-title":"Use of cognitive enhancers for mild cognitive impairment: Protocol for a systematic review and network meta-analysis","volume":"1","author":"Tricco","year":"2012","journal-title":"Syst. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/S0140-6736(06)68542-5","article-title":"International Psychogeriatric Association Expert Conference on mild cognitive impairment. Mild cognitive impairment","volume":"367","author":"Gauthier","year":"2006","journal-title":"Lancet"},{"key":"ref_10","first-page":"641","article-title":"Factors Associated with Mild Cognitive Impairment among Elderly Patients Attending Medical Clinics in Universiti Kebangsaan Malaysia Medical Centre","volume":"41","author":"Rosdinom","year":"2012","journal-title":"Sains Malays."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1146\/annurev.clinpsy.1.102803.144039","article-title":"Mild cognitive impairment and dementia","volume":"2","author":"Albert","year":"2006","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1479-8301.2012.00417.x","article-title":"Cautious notification and continual monitoring of patients with mild cognitive impairment","volume":"12","author":"Odawara","year":"2012","journal-title":"Psychogeriatrics"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Irish, M., Lawlor, B.A., Coen, R.F., and O\u2019Mara, S.M. (2011). Everyday episodic memory in amnestic mild cognitive impairment: A preliminary investigation. BMC Neurosci., 12.","DOI":"10.1186\/1471-2202-12-80"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1365-2796.2004.01380.x","article-title":"Mild cognitive impairment-beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment","volume":"256","author":"Winblad","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1001\/jama.2014.13806","article-title":"The diagnosis and management of mild cognitive impairment. A clinical review","volume":"312","author":"Langa","year":"2014","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1001\/archneur.58.12.1985","article-title":"Current concepts in mild cognitive impairment","volume":"58","author":"Petersen","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Savaskan, E., Summermatter, D., Schroeder, C., and Sch\u00e4chinger, H. (2018). Memory deficits for facial identity in patients with amnestic mild cognitive impairment [MCI]. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195693"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s11920-014-0490-8","article-title":"Mild cognitive impairment: Diagnosis, longitudinal course, and emerging treatments","volume":"16","author":"Vega","year":"2014","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1111\/jgs.12878","article-title":"Can performance on daily activities discriminate between older adults with normal cognitive function and those with mild cognitive impairment?","volume":"62","author":"Rodakowski","year":"2014","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_20","first-page":"7","article-title":"Cholinesterase inhibitors for mild cognitive impairment","volume":"12","author":"Russ","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1503\/cmaj.130451","article-title":"Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: A systematic review and meta-analysis","volume":"185","author":"Tricco","year":"2013","journal-title":"Can. Med. Assoc. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1192\/bjp.bp.113.127811","article-title":"Treatment for mild cognitive impairment: Systematic review","volume":"203","author":"Cooper","year":"2013","journal-title":"Br. J. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/joim.12190","article-title":"Mild cognitive impairment: A concept in evolution","volume":"275","author":"Petersen","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_25","first-page":"1","article-title":"Italian standardization of neuropsychological tests","volume":"8","author":"Spinnler","year":"1987","journal-title":"Ital. J. Neurol Sci."},{"key":"ref_26","unstructured":"Rey, A. (1964). L\u2018Examen Clinique En Psychologie [Clinical Tests in Psychology], Presses Universitaries De France."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jamda.2016.06.020","article-title":"Spontaneous Reversion of Mild Cognitive Impairment to Normal Cognition: A Systematic Review of Literature and Meta-Analysis","volume":"17","author":"Canevelli","year":"2016","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.fct.2018.07.010","article-title":"Targeting ERK signaling pathway by polyphenols as novel therapeutic strategy for neurodegeneration","volume":"120","author":"Farzaei","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13195-017-0241-2","article-title":"Role of neuroinflammation in neurodegeneration: New insights","volume":"9","author":"McManus","year":"2017","journal-title":"Alzheimers Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.21010\/ajtcam.v14i4.17","article-title":"Protective effect of iris germanica l. In \u03b2-amyloid-induced animal model of Alzheimer\u2019s disease","volume":"14","author":"Borhani","year":"2017","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_31","first-page":"S26","article-title":"How does brain insulin resistance develop in Alzheimer\u2019s disease?","volume":"10","author":"Lourenco","year":"2014","journal-title":"Alzheimers Dement."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s00702-013-1147-1","article-title":"Mechanisms of action of brain insulin against neurodegenerative diseases","volume":"121","author":"Ramalingam","year":"2014","journal-title":"J. Neural Transm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1001\/jamaneurol.2015.1807","article-title":"Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease","volume":"72","author":"Tuszynski","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1161\/HYPERTENSIONAHA.112.193060","article-title":"Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: The Cocoa, Cognition, and Aging [CoCoA] study","volume":"60","author":"Desideri","year":"2012","journal-title":"Hypertension"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3945\/ajcn.114.092189","article-title":"Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: The Cocoa, Cognition, and Aging (CoCoA) Study\u2014A randomized controlled trial","volume":"101","author":"Mastroiacovo","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.3390\/ijms11041321","article-title":"Bioavailability of.the polyphenols: Status and controversies","volume":"11","author":"Filesi","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.lfs.2016.07.021","article-title":"Polyphenols in dementia: From molecular basis to clinical trials","volume":"161","author":"Molino","year":"2016","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2009.10.003","article-title":"Flavonoids and cognition: The molecular mechanisms underlying their behavioural effects","volume":"492","author":"Spencer","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1111\/j.1471-4159.2006.03870.x","article-title":"Common molecular mechanisms in explicit and implicit memory","volume":"97","author":"Barco","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.jep.2013.11.008","article-title":"Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract","volume":"151","author":"Kongkeaw","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"365","DOI":"10.21101\/cejph.a4414","article-title":"Is Mild Cognitive Impairment a Precursor of Alzheimer\u2019s Disease? Short Review","volume":"23","author":"Janout","year":"2015","journal-title":"Cent. Eur. J. Public Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3233\/JAD-180513","article-title":"Depressive Symptoms in Mild Cognitive Impairment and the Risk of Dementia: A Systematic Review and Comparative Meta-Analysis of Clinical and Community-Based Studies","volume":"67","author":"Tan","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Arevalo-Rodriguez, I., Smailagic, N., Roqu\u00e9 IFiguls, M., Ciapponi, A., Sanchez-Perez, E., Giannakou, A., Pedraza, O.L., Bonfill Cosp, X., and Cullum, S. (2015). Mini-Mental State Examination (MMSE) for the detection of Alzheimer\u2019s disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst. Rev., CD010783.","DOI":"10.1002\/14651858.CD010783.pub2"},{"key":"ref_44","first-page":"57","article-title":"Elman neural network for the early.identification of cognitive impairment in Alzheimer\u2032s disease","volume":"29","author":"Lamponi","year":"2014","journal-title":"Funct. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.3233\/JAD-160305","article-title":"Promising Role of Neuromodulation in Predicting the Progression of Mild Cognitive Impairment to Dementia","volume":"53","author":"Naro","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3233\/JAD-170973","article-title":"Evaluating Peripersonal Space through the Functional Transcranial Doppler: Are We Paving the Way for Early Detecting Mild Cognitive Impairment to Dementia Conversion?","volume":"62","author":"Marra","year":"2018","journal-title":"J. Alzheimers Dis."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/5\/156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:53:11Z","timestamp":1760187191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/5\/156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,17]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["medicina55050156"],"URL":"https:\/\/doi.org\/10.3390\/medicina55050156","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,17]]}}}