Association between low vitamin B12 levels and cognitive impairment in elderly at the Naval Medical Center of Peru

ORIGINAL ARTICLE

REVISTA DE LA FACULTAD DE MEDICINA HUMANA 2023 - Universidad Ricardo Palma
10.25176/RFMH.v23i2.5650

ASSOCIATION BETWEEN LOW VITAMIN B12 LEVELS AND COGNITIVE
IMPAIRMENT IN ELDERLY AT THE NAVAL MEDICAL CENTER OF
PERU

ASOCIACIÓN ENTRE EL BAJO NIVEL DE VITAMINA B12 Y DETERIORO COGNITIVO EN ADULTOS MAYORES
DEL CENTRO MÉDICO NAVAL DEL PERÚ

Andrés Cabrera-Gamonal ORCID 1a, Carlos D. Neyra-Rivera ORCID 2b,
Jose S. Lazarte ORCID 1a
Ericson L Gutierrez ORCID 1c
Fernando M. Runzer-Colmenares ORCID 3,4d
José F. Parodi ORCID 4d

1Faculty of Medicine, Universidad de San Martin de Porres, Lima, Peru.
2Universidad Privada Peruano Alemana, Lima, Peru.
3CHANGE Research Working Group, Degree in Human Medicine, Faculty of Health Sciences, Universidad Científica del Sur, Lima, Peru.
4Faculty of Medicine, Universidad de San Martín de Porres. Centro de Investigación del Envejecimiento (CIEN). Lima, Peru.
aSurgeon.
bBiologist. Master in University Teaching and Educational Management. Doctor in Molecular Biology and Biotechnology.
cPhysician Specialized in Health Management.
dGeriatrician.

ABSTRACT

Introduction: Older adults are susceptible to malnutrition and vitamin deficiency. Objective: To determine the association between the low level of vitamin B12 and cognitive deterioration in older adults from the Naval Medical Center, located in Lima-Peru, in the period 2010-2015. Methods: An analytical cross-sectional study was carried out, based on a secondary analysis of the Texas-Cemena UTMB 2010-2015 database of the Center for Research on Aging (CIEN) of the University of San Martín de Porres. To quantify the cognitive impairment variable, the MiniMental Test was used. To analyze the association, the Chi-square test and Poisson regression were performed. Results: 57.6% of the patients were male and the mean age was 78 ± 8.4. 41.2% presented cognitive deterioration and 9.5% of the patients presented vitamin B12 deficiency. The factors independently associated with cognitive impairment were a history of cerebrovascular disease (PR= 1.38 95% CI [1.24-1.53]), depression (PR= 1.88 95% CI [1.80-1 .97]) and vitamin B12 deficiency (PR = 1.10 95% CI [1.01-1.20]). Conclusions: In the present study, an association was found between a low level of vitamin B12 and cognitive deterioration in older adults.

Keywords: Elderly, Cognitive impairment, Naval Medicine, Geriatrics, Peru. (Source: MeSH NLM)


RESUMEN

Introducción: Los adultos mayores son suscepctibles a la malnutrición y el déficit de vitaminas. Objetivo: Determinar la asociación entre el bajo nivel de vitamina B12 y el deterioro cognitivo en adultos mayores del Centro Médico Naval, ubicado en Lima-Perú, en el periodo 2010-2015. Métodos: Se realizó un estudio transversal analítico, a partir de un análisis secundario de la base de datos Texas-Cemena UTMB 2010-2015 del Centro de Investigación del Envejecimiento (CIEN) de la Universidad de San Martín de Porres. Para la cuantificación de la variable de deterioro cognitivo se utilizó el MiniMental Test. Para analizar la asociación, se realizó la prueba de Chi cuadrado y la regresión de Poisson. Resultados: El 57,6% de los pacientes fueron de sexo masculino y la edad promedio fue de 78 ± 8,4. El 41,2% presentó deterioro cognitivo y el 9,5% de los pacientes presentó déficit de vitamina B12. Los factores independientemente asociados al deterioro cognitivo fueron el antecedente de enfermedad cerebro vascular (RP= 1,38 IC 95% [1,24-1,53]), depresión (RP = 1,88 IC 95% [1,80-1,97]) y déficit de vitamina B12 (RP = 1,10 IC 95% [1,01-1,20]). Conclusiones: En el presente estudio se encontró asociación entre un bajo nivel de vitamina B12 y el deterioro cognitivo en adultos mayores.

Palabras Clave: Anciano, Deterioro cognitivo, Geriatría, Medicina Naval, Perú. (Fuente: DeCS – BIREME)


INTRODUCTION

The population of elderly has increased worldwide in recent decades, and it is estimated that this growth will continue in the coming years. According to the World Health Organization (WHO), in the year 2000, older adults accounted for 10% of the global population (1). In Peru in 2020, older adults represented 11% of the population, corresponding to approximately 3,613,000 individuals. The increase in this population is attributed to the demographic transition taking place in Peru (2).

Elderly are highly susceptible to malnutrition and specific nutritional deficiencies. Vitamin B12 deficiency is caused by decreased absorption due to age-related factors such as hypochlorhydria or intrinsic factor deficiency (3).

Cobalamin or vitamin B12 plays an important role in the development and maturation of the central nervous system, neurotransmitter metabolism, and red blood cell formation. Cobalamin deficiency in older adults is associated with neurological manifestations, metabolic disorders, megaloblastic anemia, cardiovascular diseases, and mental disorders (3-6).

In Peru, there is a lack of information regarding the association between vitamin B12 deficiency and cognitive impairment, despite the negative impact of this deficiency on the quality of life of older adults. The information obtained in this study aims to raise awareness about this issue and contribute to addressing this public health problem.

Based on the above, the following research is proposed with the objective of determining the association between low vitamin B12 levels and cognitive impairment in elderly at the Naval Medical Center of Peru, Lima, 2010-2015.


METHODOLOGY

Design and Study Area

A cross-sectional analytical study was conducted based on the secondary analysis of a database from Texas-Cemena UTMB 2010-2015, obtained from the Center for Aging Research at Universidad San Martin de Porres.

Population and Sample

The population consisted of older adults registered in the database, including clinical and epidemiological data of individuals aged 60 and above, who received outpatient care and attended the Day Clinic (outpatient service) from June 2010 to December 2015 at the Geriatrics Service of the Center. For this study, no sampling was performed, and all registered patients in the database were included.

The study included older adults from the Naval Medical Center of Peru, including non-military patients, retired military personnel, and family members of the Naval Medical Center of Peru. Records with incomplete or incorrect data were excluded, as well as those meeting criteria for hospitalization and home visits. Ultimately, 1,553 records were included.

Variables and Instruments

Cognitive impairment was considered as the dependent variable, and sociodemographic characteristics were considered as independent variables. These characteristics included: age (senior (60-74 years), elderly (75-90 years), and oldest-old (above 91 years)) (7), sex (male and female), years of education (less than 11 years and more than 11 years), and pathological history including: diabetes (yes and no), hypothyroidism (yes and no), and cerebrovascular disease (yes and no). This measurement was previously used in a published research with the same study population (8).

The Mini-Mental State Test (MMST) was used for the quantification of cognitive impairment, which ranges from 0 to 30 points, and it was measured using the adapted version validated in Spain. A cutoff score of 24 points was used as a screening for cognitive impairment, classifying scores below 24 as cognitive impairment (9).

The Geriatric Depression Scale by Yesavage was used for assessing depression, which has been previously used in the Peruvian population. This scale consists of 5 closed-ended questions that inquire about the presence or absence of depression in older adults, and it was considered positive if patients obtained a score greater than or equal to 2. This classification was previously used in a published research with the same study population (9).

On the other hand, the variable "vitamin B12" was quantified as <150 pmol to define low levels, compared to individuals with normal levels of vitamin B12. This classification was used in a previous study (10).

Procedures

A secondary analysis of the Texas-Cemena UTMB 2010-2015 database from the Center for Aging Research at Universidad de San Martín de Porres was conducted. The database was derived from a structured instrument developed by the researchers of the original study.

Statistical Analysis

The SPSS V20.0 software was used for data processing. Descriptive statistics were performed, including the calculation of frequencies, percentages, dispersion, and measures of central tendency. The association between variables was assessed using the chi-square test.

To identify independently associated factors with cognitive impairment, a Poisson regression with robust variance was conducted, calculating crude and adjusted prevalence ratios (PR). The calculations were performed with a 95% confidence level. Regarding statistical power, it was measured using Epidat software version 4.2, assuming a frequency of vitamin B12 deficiency in individuals with cognitive impairment of 87.8% and 7.6% in individuals without cognitive impairment, with a 95% confidence interval. The calculated power was 100%.

Ethical Considerations

Approval was obtained from the Research Ethics Committee of the Faculty of Medicine at Universidad San Martin de Porres.


RESULTS

The majority of patients seen were male, accounting for 57.6% of the sample, and the average age was 78 ± 8.4 years. Most patients were classified as elderly (75-90 years), representing 64.4% of the sample. Additionally, the majority had more than 11 years of education, accounting for 72.5%. Finally, the main pathologies observed in the study among the older adult patients are described. Diabetes mellitus was present in 18.3% of cases. Hypothyroidism was present in only 11% of all patients. Cerebrovascular disease was observed in 4.4% of the patients. Depression was present in 25.2% of the patients. As for the Mini-Mental State Test, 41.2% showed cognitive impairment. Regarding vitamin B12 levels, 90.5% of the patients did not have a vitamin B12 deficiency (Table 1).


Table 1. General characteristics of elderly.

Variables

N

%

Sex

 

 

Female

659

42.40%

Male

894

57.60%

Age

 

 

Senior

445

28.70%

Elderly

1 000

64.40%

Oldest Old

108

7.00%

Education

 

 

≤11 years

427

27.50%

>11 years

1 126

72.50%

Diabetes Mellitus

 

No

1 269

81.70%

Yes

284

18.30%

Hypothyroidism

 

 

No

1 392

89.00%

Yes

171

11.00%

Cerebrovascular Disease

No

1 484

95.60%

Yes

69

4.40%

Depression

 

 

No

1 162

74.80%

Yes

391

25.20%

Cognitive Impairment

 

Yes

640

41.20%

No

905

58.30%

Vitamin B12 Levels

 

Deficiency

147

9.50%

No Deficiency

1 406

90.50%

Total

1 553

100%




Table 2 describes the variables in relation to MMSE ≤ 24, showing an association between hypothyroidism (p<0.001), cerebrovascular disease (p<0.001), depression (p<0.0001) and vitamin B12 (P=0.003) with cognitive impairment.




Table 2. General characteristics of patients in relation to cognitive impairment.

Variables

MMSE* ≤ 24

MMSE* >24

p value

(Cognitive Impairment)

(No Cognitive Impairment)

N

%

N

%

Sex

 

 

 

 

0.318

Female

263

41.10%

395

43.60%

 

Male

377

58.90%

510

56.40%

 

Age

 

 

 

 

0.691

Senior

177

29.10%

254

28.10%

 

Elderly

406

63.40%

591

65.30%

 

Oldest Old

48

7.50%

60

6.60%

 

Education

 

 

 

 

0.951

≤11

177

27.70%

249

27.50%

 

>11 years

463

72.30%

656

72.50%

 

Diabetes Mellitus

 

 

 

0.711

No

520

81.30%

742

82.00%

 

Yes

120

18.80%

163

18.00%

 

Hypothyroidism

 

 

 

˂0.0001

No

519

81.10%

855

94.50%

 

Yes

121

18.90%

50

5.50%

 

Cerebrovascular Disease

 

 

˂0.0001

No

579

90.50%

897

99.10%

 

Yes

61

9.50%

8

0.90%

 

Depression

 

 

 

 

˂0.0001

No

289

45.20%

895

95.60%

 

Yes

351

54.80%

40

4.40%

 

Vitamin B12

 

 

 

 

0.003

No Deficiency

78

12.20%

836

92.40%

 

Deficiency

562

87.80%

69

7.60%

 

*MMSE: Mini-Mental Test Examination



The factors independently associated with cognitive impairment were a history of cerebrovascular disease (PR = 1.375, 95% CI [1.239-1.527]), depression (PR = 1.881, 95% CI [1.796-1.971]), and vitamin B12 deficiency (PR = 1.102, 95% CI [1.012-1.200]) (Table 3).

Table 3. Factors associated with cognitive impairment in older adults.

Variable

           Crude Model

          Adjusted Model

p value

PR [IC95%]

P value

PR [IC95%]

Male sex

0.318

1.11[0.90-1.63]

0.269

1.03[0.98-1.08]

Age

       

Oldest Old

0.684

1.02[0.92-1.13]

0.879

1.01[0.91-1.11]

Elderly

0.583

0.99[0.93-1.04]

0.525

0.98[0.93-1.04]

Education >11 years

0.951

1.00[0.91-1.10]

0.327

1.03[0.98-1.08]

Diabetes Mellitus

0.711

1.02[0.94-1.14]

0.645

1.01[0.96-1.08]

Hypothyroidism

˂0.0001

2.13[1.68-2.70]

0.748

0.99[0.91-1.06]

Cerebrovascular Disease

˂0.0001

5.24[2.73-10.07]

˂0.0001

1.80[1.24-1.53]

Depression

˂0.0001

7.33[5.45-9.85]

˂0.0001

1.88[1.80-1.98]

Vitamin B12 Deficiency

0.003

1.28[1.07-1.52]

0.025

1.10[1.01-1.20]

DISCUSSION

The present study found an association between low levels of vitamin B12 and cognitive impairment. Additionally, an association was found between a history of cerebrovascular disease (CVD) and depression with cognitive impairment. Vitamin B12 and folic acid are crucial in the methylation processes of the central nervous system, and their deficiency can lead to neuropsychiatric disorders and vascular cognitive impairment due to hyperhomocysteinemia and excitotoxic mechanisms (11). Previous studies have also described the association between cobalamin levels and cognitive function. Meertens et al. conducted a study in a nursing home in Venezuela (12), Vogel et al. conducted a longitudinal study in Spain (13) and Aguilar et al. conducted a study in outpatient patients at a hospital in Mexico (14) all finding a significant relationship between low cobalamin levels and cognitive function.

Silva et al. (15) also found that vitamin B12 deficiency is common in older individuals and can lead to reversible dementia. In older adults aged 60 years and above with dementia, the prevalence of vitamin B12 deficiency has been determined to be 7.5%. Significant improvement in the median MMSE score was observed at 6 weeks and 12 weeks after vitamin B12 supplementation (16). This is explained by the fact that vitamin B12 deficiency leads to elevated homocysteine levels, which are a risk factor for vascular disease and cause DNA damage in the brain (17).

Finally, this study found an association between cognitive impairment and a history of cerebrovascular disease (CVD). In Japan, the prevalence of cognitive impairment after a 3-year follow-up following a stroke increased with advanced age. Previous studies have also reported that the prevalence of cognitive impairment following a stroke ranges from 20% to 80% (18). Therefore, as a result of the high rates of mortality and disability associated with stroke occurrence, managing significant risk factors is of utmost importance in older adults (19).

Similarly, vitamin B12 supplementation could be beneficial in reversing these symptoms in older adults. A case presented by Behres et al. at a hospital in Chile showed that treatment with parenteral cobalamin and vitamin B9 reversed the symptoms, leading to normal results in neuropsychological tests and consequently reintegrating the individual into their work (20). Additionally, vitamin B supplements have been found to delay or maintain cognitive decline in older adults (21). However, it is indicated that higher dietary intake of folate, but not B12 or B6, is associated with a reduced risk of dementia in the elderly population without dementia, thus requiring further studies (22).

Among the limitations of the present study, it was found that some variables could not be measured due to missing data in the original database or were unrelated to the patient. Additionally, this study was conducted at a military hospital in Peru, which may have some differences compared to findings in public hospitals under the Ministry of Health or the Social Health Insurance (EsSalud). However, these older adults represent a significant percentage of patients living in middle-class areas of Lima, where there is a considerable increase in the elderly population. Therefore, the results are important for obtaining an approximation of the influence of vitamin B12 on cognitive impairment in this population.

CONCLUSIONS

In this population, an association was found between low levels of vitamin B12 and cognitive impairment. These findings may indicate the influence of cobalamin on cognition in geriatric patients, as well as the potential usefulness of vitamin supplementation in slowing the progression of cognitive disorders in older adults.


Authorship Contributions: JS-O participated in the conception of the article, the collection of data, its writing and approval of the final version. VQ-S participated in the conception of the article, the data collection, its writing and approval. of the final version. MT-L participated in the conception of the article, the data collection, its writing and approval. of the final version. IM-O participated in the drafting and approval of the final version ML-E participated in the analysis data statistician, his Drafting and approval of the final version. PR-C participated in the conception of the article, the data collection, your Drafting and approval of the final version.
Financing: This research did not receive any specific grant from any financing agency in the sectors public, commercial or non-profit.
Conflict of interests: None of the other authors reported a conflict of interest. related to this study. The authors certify that there is no conflict of interest with any financial organization with respect to the material discussed in the manuscript.
Received: February 13, 2022.
Approved: April 23, 2023.


Corresponding author: Ericson Gutierrez Ingunza.
Address: Facultad de Medicina USMP. Alameda del Corregidor 1531, La Molina 15024.
Phone: +90 553 437 5414
E-mail: eringunza@yahoo.es


Article published by the Journal of the faculty of Human Medicine of the Ricardo Palma University. It is an open access article, distributed under the terms of the Creatvie Commons license: Creative Commons Attribution 4.0 International, CC BY 4.0 (https://creativecommons.org/licenses/by/1.0/), that allows non-commercial use, distribution and reproduction in any medium, provided that the original work is duly cited. For commercial use, please contact revista.medicina@urp.edu.pe.


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