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Artikel Penelitian

Maj Kedokt Indon, Volum: 58, Nomor: 3, Maret 2008

Dietary Vitamins B, Folic Acid andCognitive Impairment in the Elderly

Jowy Tani, Irwin Tedja, Ivan Riyanto Widjaja,Saptawati Bardosono, Zarni Amri

Faculty of Medicine, University of Indonesia,

Abstract: Vitamin B1 and B6 may play vital roles in the functioning of nervous system, and low

plasma levels of vitamin B12 and folic acid have been linked with higher homocysteine level and

deterioration of cognitive functioning. This cross-sectional study was designed to investigate

the relationship between dietary intake of vitamin B1, B6, B12, folic acid and the presence of

cognitive impairment in the elderly. A total of 27 participants from a nursing home in Jakarta

participated in the study. Daily intake levels of vitamin B1, B6, B12, and folic acid was obtained

using Semiquantitative Food Frequency Questionnaire (SFFQ), while cognitive functioning of

the participants was determined using Mini Mental State Examination (MMSE). Age, sex, edu-cation, body mass index, and macronutrients intake were not associated with the presence of

cognitive impairment. Higher intake of vitamin B6 was associated with lower incidence of

cognitive impairment (p=0.016). No association between vitamin B1 (p=0.138), B12 (p=0.490),

and folic acid (p=0.146) intake level and the presence of cognitive impairment was found.

Higher intake of vitamin B6 may be protective against cognitive impairment caused by aging,

prompting further study concernng beneficial effects of vitamin B6. Beneficial effects of vitamin

B12 and folic acid intake in the prevention of cognitive impairment remain unproven.

Keywords:vitamin B6, vitamin B12, folic acid, cognition, elderly

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Asupan Vitamin B, Asam Folat, dan Gangguan Kognitif pada Lansia

Jowy Tani, Irwin Tedja, Ivan Riyanto Widjaja,Saptawati Bardosono, Zarni Amri

Fakultas Kedokteran Universitas Indonesia,

Abstrak: Vitamin B1 dan B6 berperan penting dalam fungsi saraf. Kadar vitamin B12 dan asam

folat dalam plasma darah yang rendah berhubungan dengan kadar homosistein yang tinggi dan

perburukan fungsi kognitif. Penelitian potong lintang ini dirancang untuk meneliti hubungan

antara asupan vitamin B1, B6, B12, dan asam folat dengan timbulnya gangguan kognitif pada

lansia. Sejumlah 27 peserta dari sebuah rumah jompo di Jakarta berpartisipasi dalam penelitian

ini. Tingkat asupan harian nutrient-nutrien diperoleh menggunakan Semiquantitative Food

Frequency Questionnaire (SFFQ). Fungsi kognitif diperoleh dengan menggunakanMini Men-

tal State Examination (MMSE). Usia, jenis kelamin, pendidikan, indeks massa tubuh, dan

asupan makronutrien tidak berhubungan dengan gangguan kognitif. Asupan vitamin B6 yanglebih tinggi berhubungan dengan kejadian gangguan kognitif yang lebih rendah (p=0.016). Tidak

ditemukan hubungan antara vitamin B1 (p=0.138), B12 (p=0.490), dan asam folat (p=0.146)

dengan gangguan kognitif. Asupan vitamin B6 mungkin bersifat protektif terhadap gangguan

kognitif akibat penuaan. Manfaat asupan vitamin B12 dan asam folat dalam pencegahan gangguan

kognitif masih belum terbukti.

Kata kunci:vitamin B1, vitamin B6, vitamin B12, asam folat, kognisi, lansia

Dietary Vitamins B, Folic Acid and Cognitive Impairment in the Elderly

Introduction

Cognitive impairment in the elderly is a global problem

with wide implication. Individuals affected by such impair-

ment would experience declination of cognitive function as

they age. Productivity of the affected individuals would de-

crease as their cognitive function continues to deteriorate,

and a number of them would finally develop complete de-

pendency on others, placing enormous burden on the soci-

ety as a whole. Indonesia, as one of the countries where

geriatric population is increasing faster than the newborns,

needs to pay particular concern to this problem.1

As cognitive impairment caused by aging is generally

considered an irreversible process, attention has been fo-

cused on the prevention of cognitive impairment. Adequate

intake of certain nutrients may be one of the factors that may

delay or prevent the onset of cognitive impairment in the

elderly. Dietary intake of certain antioxidant nutrients had

been associated with better cognitive functioning.2It was

also proposed that adequate dietary intake of several B vita-

mins and folic acid may also be able to provide similar ef-

fects.

Several B vitamins have been linked with the nervous

system and cognitive functioning. Vitamin B1 (thiamine) plays

important role in neurotransmission and nerve conduction,

and deficiency of the nutrient causes Wernicke-Korsakoff

syndrome.3Vitamin B6 (pyridoxine) is involved in the syn-

thesis of several neurotransmitter, and is required in the de-

velopment of nervous system.4A number of studies revealed

that lower vitamin B12 (cobalamin) and folic acid plasma level

were associated with higher incidence of cognitive impair-

ment.5It was suggested that deficiency of dietary vitamin

B12 and folic acid may cause increment of homocysteine

plasma level.6Several study has found that higher plasma

level of homocysteine were associated with higher incidenceof cognitive impairment.7,8Elevated homocysteine plasma

level, as an established cardiovascular risk factor, may in-

crease the risk of Alzheimers disease and vascular dementia,

the two conditions that caused the majority cases of cogni-

tive impairment in the elderly.9,10However, while association

between plasma level of vitamin B12 and folic acid with cog-

nitive impairment was recognized in several studies, clinical

study investigating the role of dietary folic acid and vitamin

B12 in cognitive impairment show conflicting results.11,12To

our knowledge, no study investigating long time dietary pat-

tern of the B vitamins and folic acid in Indonesian elderly

population had been conducted before, especially with par-

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ticipants that never took supplements containing the B vita-

mins and/or folic acid. Therefore we conducted this cross-

sectional study to investigate the association between cog-

nitive impairment with dietary pattern of the B vitamins andfolic acid. It was hoped that we could provide scientific evi-

dence for the benefit of dietary pattern rich in the B vitamins

and folic acid. The result of the study may also prompt phy-

sicians to placed additional caution on individuals with par-

ticular dietary pattern which may put the individual at risk of

cognitive impairment.

Methods

Population

All study participants were residents of a nursing home

located in Cibubur, Jakarta, Indonesia. The total population

of the nursing home was 77 at the time of the study. Allnursing home residents aged at least 60 years old at the time

of the study, had formal education more than 4 years, and

had not taken supplements containing vitamin B1, B6, B12,

and/or folic acid were eligible for participation in the study.

All nursing home residents (N=27) fulfilling the inclusion

criteria consent to the participation in the study and signed

the written informed consent to be included in the study. All

data was obtained at March 2007. Data obtained from par-

ticipants included age, sex, education (year of formal educa-

tion taken), anthropometric measurement (body weight, body

height, and body mass index [BMI]), dietary assessment,

and cognitive function assessment. The study has obtained

ethical clearance from Department of Community Medicine,

Faculty of Medicine University of Indonesia.

Dietary Assessment

To obtain long-term dietary pattern of the participants,

a Semi-quantitative Food Frequency Questionnaire (SFFQ)

form was completed for each participant through interview

by clinical year medical students. The SFFQ form recorded

all food items that had been consumed during the one week

duration prior to the interview, the frequency of its con-

sumption, and the portion consumed, based on participants

recall.13The SFFQ also recorded whether any ingredient

contained in any particular food item was not consumed.

Initial food items listed in the SFFQ were based on food

menu record that had been provided by the nursing home

administrator. Food items consumed not listed in the initial

list were added during the interview. Three-dimensional food

model was used as an aid in the interview process.

The SFFQ data were then converted to macronutrients,

vitamin B1, B6, B12, and folic acid daily intake values using

NutriSurvey software (1995, Erhardt J, University of Indone-

sia, SEAMEO-TROPMED) based on United States Depart-

ment of Agriculture National Nutrient Database Standard

Reference Release-19.

Cognitive Function Assessment

Mini Mental State Examination (MMSE) was used to

assess the cognitive functioning of the participants.14The

administration of MMSE was done by clinical year medicalstudents who had been trained for the task.

The presence of cognitive impairment in the study par-

ticipants was determined by applying a cut-off point to par-

ticipants MMSE score; a participant was considered affected

by cognitive impairment if the participants MMSE score is

lower than the cut-off point. The cut-off point used in our

study would be based on the study result by Crum.15The

25thpercentile value of the group in the Crum 15 study, as

presented in table 1, which mean (or median, depending on

the normality of the data distribution) values of age and edu-

cation of our study population fitted in, would be use as the

cut-off point. This was done to reflect the effects of age andeducation on the MMSE score of the population.

Table 1. Selected 25th Percentile Scores on MMSE by Age andEducational Level from the Crum Study15

Educational AgeLevel 60-64 65-69 70-74 75-79 80-85 e85

0-4 year 19 19 19 18 16 15

5-8 year 24 24 24 22 22 21

9-12 year 27 27 26 25 23 23

>12 year 28 28 27 27 26 25

Mini Mental State Examination

Data Analysis

To determine the possible effects of age and education

on the presence of cognitive impairment, we analyzed the

associations of age and education with the presence of cog-

nitive impairment using independent samples T-test or Mann

Whitney test, as appropriate. As to determine the associa-

tions of sex with the presence of cognitive impairment, Chi-

square or Fishers exact test was used.

The associations between daily intake values of macro-

nutrients, vitamin B1, B6, B12, and folic acid and the pres-

ence of cognitive impairment were determined using inde-pendent samples T-test or Mann Whitney test, depend on

the normality of the data distribution. All statistical analysis

in the study was performed using SPSS for Windows ver-

sion 14 (SPSS Inc, Chicago, Illinois).

Results

The baseline characteristics of the participants are pre-

sented in table 2. The mean for age was 76.93 years and

median for education was 12 years. Most participants (77.78%)

were female (n=21), and 14 (51.85%) of them had cognitive

impairment.

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Table 2. Baseline Characteristics of the Sample (n = 27)

Characteristic Number (%)

Age, mean (SD), y 76.93 (7.15)Female (%) 21 (77.78)

Education, median (interquartile range), y 12 (5)

Weight, median (interquartile range), kg 53.45 (16 .95)

Height, median (interquartile range), cm 150.75 (6.90)

BMI , median (interquartile range), kg/m2 24.17 (6.74)

IntakeTotal energy, median (interquartile range), cal/d 1440.40 (50 8.7 0)

Carbohydrate, mean (SD), g/d 189.84 (55.07)

Protein, mean (SD), g/d 51.74 (13.16)

Fat, median (interquartile range), g/d 59.40 (22.30)

Vitamin B1, mean (SD), mg/d 0.99 (0.37)

Vitamin B6, median (interquartile range), mg/d 1.40 (0.20)

Vitamin B12, mean (SD), mg/d 3.20 (3.50)

Folic acid, mean (SD), mg/d 295.50 (104.45)

Cognitive impairment present (%) 14 (51.85)

MMSE score, mean (SD) 27.00 (2.97)

Body Mass IndexMini Mental State Examination

Association between age, education, BMI, and daily

nutritional intake values with presence of cognitive impair-

ment are presented in table 3. No significant association of

age (p=0.134), education (p=0.068), BMI (p=0.262) and daily

intake values of total energy (p=0.435), carbohydrate

(p=0.050), protein (p=0.283), and fat (p=0.435) with the pres-

ence of cognitive impairment were found. The association

between sex and the presence of cognitive was also notsignificant (p=0.662).

Table 3. Association of Age, Education, BMI, and Daily Nutritional Intake Values with Presence of Cognitive Im-pairment

Cognitive Impairment Present Not Present p valueMeanSD MeanSD

Age (y) 79.255.99 75.077.65 0.134

Education (y) 11.082.54 13.132.56 0.068

BMI 23.923.19 25.824.97 0.262

Total energy (cal/d) 1355.59301.13 1468.01483.67 0.435

Carbohydrate (g/d) 16 6.7 83 6.1 4 2 08. 296 1.5 3 0 .0 50Protein (g/d) 48.6510.17 54.2115.01 0.283

Fat (g/d) 57.0616.74 62.8416.63 0.435

Vitamin B1 (mg/d) 0.880.25 1.090.42 0.138

Vitamin B6 (mg/d) 1.280.24 1.560.26 0.016

Vitamin B12 (mg/d) 2.670.81 3.634.67 0.490

Folic acid (mg/d) 262.5382.93 321.88114.80 0 .1 46

Body Mass Index

For association between intake of the B vitamins, folic

acid and the presence of cognitive impairment, daily intake

value of vitamin B6 were found to be significantly associ-

ated with the presence of cognitive impairment (p=0.016).

Higher intake of vitamin B6 was associated with lower inci-

dence of cognitive impairment in the participants. However,

daily intake value of vitamin B1 was not significantly associ-

ated with presence of impairment in the participants (p=0.138).

Neither do vitamin B12 nor folic acid were significantly asso-ciated with the presence of cognitive impairment (p=0.490

and p=0.146, respectively).

Discussion

Our study showed that higher intake of vitamin B6 was

associated with lower incidence of cognitive impairment in

the participants. No association between other B vitamins

and folic acid was demonstrated in our study. Several stud-

ies investigating association between B vitamins and folic

acid intake with cognitive impairment has found conflicting

results. In this study, we decided to exclude the participants

that had taken supplements contained the B vitamins andfolic acid because we consider that supplements intake was

often short-term and may not reflected the participants long-

term dietary pattern.

The strengths of our study are its assessment tools and

the nursing home setting. MMSE is a relatively sensitive

and specific tool that can be used to assess a persons cog-

nitive functioning in short amount of time and its validity

have been proven in many other studies, while SFFQ is a

tool designed to provide dietary patterns of participants,

and it was expected that in this study it would be able to

provide reasonably accurate picture of the participants long-

term dietary pattern. The particular nursing home setting in

this study has a food providing policy that allowed its resi-

dent to freely decide the amount and type of food provided

they wish to consume. This is expected to reduce the possi-

bility that SFFQ may not reflect the long-term dietary habit of

the participants because of strict food providing policy. The

particular nursing home also provided us with participants

with relatively high education level, increasing the reliability

of MMSE.

However, several limitation of this study must also be

considered. First, SFFQ that was used in this study, although

reasonably valid, is not the ideal dietary assessment tool.

Comprehensive diet history would be able to obtained more

accurate dietary information. In our study, SFFQ recallingduration is limited to only one week. Even though this was

intended to reduce recall bias, as participants with dimin-

ished memory capacity may provide unreliable information if

asked to recall memory further than one week, this may de-

crease the accuracy of long-term dietary pattern that was

expected to be obtained.

Second, the study had not been able to exclude all pos-

sible confounding factors that may affected the participants

cognitive functioning, such as social activities, presence of

organic illnesses,16presence of pseudo-dementia,17alcohol

intake,18smoking habit,19mental activities,20and many other

factors that may had influenced participants cognitive func-

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tion. Finally, the relative small sample size in this study has

limited the significance of statistical inference of the avail-

able data. The study could benefit from a larger sample size.

The finding that higher intake of vitamin B6 contributeto decreased incidence of cognitive impairment in the eld-

erly may suggest vitamin B6s role in preventing cognitive

impairment. Several possible explanations could be sug-

gested based on this finding; as vitamin B6 is involved in

the development of nervous system, long-term dietary pat-

tern rich in vitamin B6 may prevent nervous system defects

during the development process, and therefore promote the

development of a central nervous system more resistant to

neurodegenerative process that lead to cognitive impairment.

Vitamin B6 also plays vital role in the synthesis of several

important neurotransmitters, including serotonin, dopamine,

and norepinephrine.4Adequate intake of vitamin B6 may

enable the synthesis of these neurotransmitters in sufficient

amount to maintain cognitive functioning.

It might also be possible that higher intake of vitamin

B6 decrease the incidence of cognitive impairment via other

mechanisms. As our study result is still of preliminary na-

ture, as suggested by its relative small sample size, more

studies, both epidemiologic and biochemical, were required

to determine the exact mechanism(s) of the protective effect.

The fact that no significant association between age,

sex, education, BMI, and macronutrients intake with the pres-

ence cognitive impairment were found suggests that these

variables may play limited role in the etiology of cognitive

impairment.Nonexistence of significant association between vita-

min B1 intake level and cognitive impairment may support

the view that as long as there is no chronic and severe defi-

ciency of vitamin B1, changes in the intake level nutrient

would not significantly alter the cognitive functioning in the

elderly.

The findings that no significant association existed

between vitamin B12 and folic acid intake and the presence

of cognitive impairment were consistent with the finding of

some of other larger studies investigating association be-

tween dietary intake of vitamin B12 and folic acid with cog-

nitive functioning.

11,12

Thus remain the fact that while lowerplasma concentration of vitamin B12 and folic acid were as-

sociated with higher incidence of cognitive impairment, as-

sociation between dietary intake level of vitamin B12, folic

acid and cognitive impairment in the elderly remain unproven.

Conclusion

In conclusion, the present result suggests that long-

term dietary pattern with higher intake of vitamin B6 may be

associated with lower incidence of cognitive impairment in

the elderly, prompting more efforts to study the potential

beneficial effect of vitamin B6 toward prevention of cogni-

tive impairment. However association between long-term

dietary intake of vitamin B1, B12, folic acid and cognitive

impairment in the elderly remain unproven.

Acknoledgement

The authors wish to thank Department of CommunityMedicine and Department of Nutrition, Faculty of Medicine,

University of Indonesia for facilitating the study. We are

also grateful to Dr. dr. Martina Wiwie S.N. and dr. Petrin R.

from Division of Geriatric Psychiatry, Department of Psy-

chiatry, Faculty of Medicine, University of Indonesia for pro-

viding counsels concerning administration of Indonesian

version of MMSE.

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