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8907422
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Pharmacol Res
Pharmacol Res
Pharmacological research
1043-6618
1096-1186

38336310
10.1016/j.phrs.2024.107103
nihpa2018326
Article
Combining choline bitartrate and vitamin B12 ameliorates cognitive impairment in hypertensive elders with cognitive frailty
Mone Pasquale 1Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, Campobasso, Italy
Department of Medicine, Einstein Institute for Aging Research, Einstein Institute for Neuroimmunology and Neuroinflammation, Albert Einstein College of Medicine, New York, USA
Casa di Cura “Montevergine”, Mercogliano (Avellino), Italy ASL Avellino, Italy

Trimarco Valentina 2Department of Neuroscience, Reproductive Sciences and Dentistry, “Federico II” University, Naples, Italy

Kansakar Urna Department of Medicine, Einstein Institute for Aging Research, Einstein Institute for Neuroimmunology and Neuroinflammation, Albert Einstein College of Medicine, New York, USA

Izzo Raffaele Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy

Santulli Gaetano *3Department of Medicine, Einstein Institute for Aging Research, Einstein Institute for Neuroimmunology and Neuroinflammation, Albert Einstein College of Medicine, New York City, NY, USA
Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy
Department of Molecular Pharmacology, Fleischer INstitute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York City, NY, USA

Trimarco Bruno 4Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy

1 Equally contributed as First Authors

2 Equally contributed as First Authors

3 Equally contributed as Last Authors

4 Equally contributed as Last Author

* Correspondence to: Albert Einstein College of Medicine, New York, USA. gsantulli001@gmail.com (G. Santulli).
3 9 2024
3 2024
07 2 2024
08 9 2024
201 107103107103
https://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
Aging
Choline
Cognitive impairment
Elderly
Frailty
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pmcFrailty is a worldwide increasing health problem leading to adverse outcomes such as cognitive impairment, particularly in older adults [1]. Cognitive frailty (CF) is a relatively novel type of frailty that refers to a condition characterized by the simultaneous presence of physical frailty and cognitive impairment, particularly in older adults [2]. CF represents a state of heightened risk for adverse health outcomes, including disability, dementia, falls, hospitalization, and mortality, compared to individuals who have either physical frailty or cognitive impairment alone. Mild cognitive impairment (MCI) is considered a transitional stage between normal cognitive aging and dementia. In elderly individuals, hypertension represents a typical comorbidity that further increases such risk, driving adverse events. Unfortunately, there is no accepted treatment for CF [3].

In a previous investigation, we evidenced the potential role of choline alphoscerate in frail hypertensive elders [4]. Choline bitartrate (CB) is one of the most common kinds of choline supplements and is known to be more absorbable than other forms [5]. Equally important, preclinical studies have reported a choline-sparing effect of Vitamin B12 (B12) supplementation, evidencing that patients with B12 deficit exhibit lower blood concentrations of choline [5]. On these grounds, we decided to test the effects of combining CB and B12 on cognitive impairment in hypertensive elders with CF. From January 2023 to December 2023, we evaluated 137 consecutive hypertensive elders with CF. We diagnosed CF in presence of MCI (defined by applying the Clinical Dementia Rating Scale, CDR: 0,5) and physical frailty (defined by the presence of at least 3 of 5 Fried Criteria [6]).

The study participants were recruited at the ASL (Local Health Authority of the Italian Ministry of Health) Avellino, Italy. Every patient or legally authorized representative signed a written informed consent. We performed this investigation following the ethical standards of the 2013 Declaration of Helsinki of the World Medical Association and in accordance with Good Clinical Practice guidelines. We obtained the approval by the Institutional Review Board of Napoli Centro. We evaluated global cognitive function at baseline and after 3 months using the MoCA test. MoCA scores range from zero to 30; a score of 26 and higher is considered normal.

All patients fulfilled the following criteria: confirmed diagnosis of hypertension and CF; age >65 years; no previous stroke and/or acute myocardial infarction, no coronary artery bypass grafting, EF >50%; Montreal Cognitive Assessment (MoCA) Score <26.

Of the screened patients, 27 did not fulfill the criteria and 11 did not give the consent to participate; a total of 99 patients successfully completed the study. We randomly assigned patients to CB + B12, Choline Alphoscerate, or no nutraceuticals. We followed-up each patient for 3 months, and at this time point we measured again the MoCA score, observing a beneficial effect of CB + B12 treatment on cognitive impairment (p < 0.001 vs baseline, Fig. 1). Patients receiving choline alphoscerate also presented significant salutary effects on cognitive impairment (p < 0.005 vs baseline). Yet, the difference at follow-up between the two treated groups was statistically significant, favoring CB + B12 (p < 0.05; Fig. 1).

Taken together, our data indicate that combining CB and B12 can improve global cognitive function in hypertensive patients with CF. Further investigations with a longer follow-up are necessary to confirm the results that we have obtained in elders with CF and hypertension as well as to extend our findings in other populations.

Funding

The Santulli’s Lab is currently supported in part by the National Institutes of Health (NIH: R01 Grants from NHLBI and NIDDK to GS). UK is supported in part by a postdoctoral fellowhip of the American Heart Association (AHA-22POST915561). This publication was also produced with the co-funding European Union – Next Generation EU, Project Age-It (to PM).

Fig. 1. Montreal Cognitive Assessment (MoCA) Score assessed in the indicated groups at baseline and after 3 months. *: p < 0.05; **: p < 0.01; ***: p < 0.005; ****: p < 0.001 (ANOVA and Tukey-Kramer post hoc test).

Declaration of Competing Interest

BT reports personal fees for speaker bureau, outside the content of the current manuscript, from Malesci, Damor, MSD, and Fidia.

CRediT authorship contribution statement

Kansakar Urna: Visualization, Validation, Investigation, Formal analysis. Trimarco Valentina: Visualization, Validation, Investigation, Formal analysis, Data curation. Santulli Gaetano: Writing – review & editing, Supervision, Resources, Project administration, Methodology, Conceptualization. Izzo Raffaele: Visualization, Methodology, Data curation. Trimarco Bruno: Visualization, Validation, Methodology, Investigation, Conceptualization. Mone Pasquale: Writing – original draft, Resources, Investigation, Formal analysis, Data curation.
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