|Year : 2019 | Volume
| Issue : 1 | Page : 55-59
Association between cognition and peripheral brain-derived neurotrophic factor in a sample of normal adults in Kano, Nigeria
Isyaku U Yarube1, Tasneem M Hassan2, Rufa'i Y Ahmad3, Lawan M Umar4, Bello M Musa4, Saleh M A Ibrahim5
1 Department of Physiology, Neuroscience and Pathophysiology Unit, College of Health Sciences, Bayero University, Zaria, Nigeria
2 Department of Physiotherapy, Aminu Kano Teaching Hospital, Zaria, Nigeria
3 Department of Physiotherapy, Bayero University, Zaria, Nigeria
4 Department of Community Medicine, Bayero University and Aminu Kano Teaching Hospital, Zaria, Nigeria
5 Department of Human Physiology, Faculty of Medicine, Ahmadu Bello University, Zaria, Nigeria
|Date of Web Publication||5-Mar-2019|
Dr. Isyaku U Yarube
Department of Physiology, Neuroscience and Pathophysiology Unit, College of Health Sciences, Bayero University, Kano
Source of Support: None, Conflict of Interest: None
Introduction: Cognition is an important physiological and social element for both humans and animals. There is paucity of literature on cognitive function in Africans. Furthermore, the molecular mechanisms involved in cognition have not been fully elucidated. Brain-derived neurotrophic factor (BDNF) has a role in neuronal plasticity and cognition. However, the relationship between cognitive performance and serum BDNF levels has not been demonstrated in an African population. This study aimed to assess cognition and BDNF level and determine their relationship in a population of healthy adult Africans. Materials and Methods: Cognitive function and BDNF were determined using Mini Mental State Examination and enzyme-linked immunosorbent assay kit, respectively. SPSS statistics was used to process data. Results: Thirty male and female volunteers with a mean age of 48.7 ± 11.32 years were studied. The median cognitive score was 24.00 (21 and 28) with no sex variation (U = 107, P = 0.833). The median value of serum BDNF concentration was 2.09 ± 0.15 ng/L and statistically the same in males and females (t = 1.276, P = 0.213). Cognitive score correlated moderately with BDNF level (r = 0.369, P = 0.045), but not with sociodemographic or anthropometric characteristics. Conclusion and Recommendation: It was concluded that the population studied had normal cognitive function, which was not affected by sociodemographic and anthropometric characteristics. BDNF was a mediator of global cognitive function and was positively associated with registration and negatively associated with language domains of cognition. Peripheral levels of BDNF may potentially serve as a biomarker and index of cognitive evaluation in clinical settings.
Keywords: Brain-derived neurotrophic factor, cognitive function, determinants of cognition, Kano, Nigeria
|How to cite this article:|
Yarube IU, Hassan TM, Ahmad RY, Umar LM, Musa BM, Ibrahim SM. Association between cognition and peripheral brain-derived neurotrophic factor in a sample of normal adults in Kano, Nigeria. Niger J Basic Clin Sci 2019;16:55-9
|How to cite this URL:|
Yarube IU, Hassan TM, Ahmad RY, Umar LM, Musa BM, Ibrahim SM. Association between cognition and peripheral brain-derived neurotrophic factor in a sample of normal adults in Kano, Nigeria. Niger J Basic Clin Sci [serial online] 2019 [cited 2020 Jan 18];16:55-9. Available from: http://www.njbcs.net/text.asp?2019/16/1/55/253412
| Introduction|| |
Cognition is an important physiological and social element for both humans and animals. Disturbances in cognition can lead to significant maladaptation to internal and external environments. Although much is known about cognition, its molecular mechanisms, including the role of brain-derived neurotrophic factor (BDNF), have not been fully elucidated. BDNF belongs in the family of neurotrophins that influences neuronal proliferation survival and differentiation by activation of several signal transduction pathways., Subsequently, it was discovered to have a role in synaptic plasticity that influences the release of neurotransmitters such as glutamate GABA. Neuroplasticity is the ability of the brain to change (be “plastic”) in structure and function from the beginning to the end of an individual's life. Neuroplasticity is important for normal healthy development, learning, memory, and recovery from brain damage.,, Because of its effect on neuroplasticity, BDNF, which also circulates in blood, is very likely to affect cognitive process. However, the relationship between cognitive performance [as measured by the Mini Mental State Examination (MMSE)] and serum levels of BDNF has not been demonstrated in an African population. This study therefore aimed to assess and determine the relationship between cognitive function and BDNF levels in a population of apparently healthy adult Africans.
| Materials and Methods|| |
Study settings and subjects
The study was conducted in Murtala Muhammad Specialist Hospital (MMSH) located within the ancient Kano city. The hospital serves the inhabitants of Kano state; surrounding states such as Jigawa, Katsina, and Kaduna; and people from countries neighboring Nigeria such as Chad and Niger Republic. MMSH has a bed capacity of about 250 and a monthly patient turnover of about 18,000. Healthy adult male and female subjects accompanying patients to the hospital were approached for the study.
Study design, sample size, and sampling
The study was descriptive and cross-sectional in design. A minimal sample size of 24 was determined for the study using computer software according to Lenth, given the mean [±standard deviation (SD)] BDNF of 1.74 ± 0.4 obtained from a pilot study and assuming statistical power of 0.8. Subjects were recruited from the outpatient clinic of the hospital using systematic sampling technique. Using the daily attendance register as the sampling frame, patients' relatives accompanying selected patients were approached for data collection. Prospective respondents above 65 years, those with history of smoking, drug abuse, diabetes, hypertension, or any mental illness were excluded from the study.
Instrument and method of cognitive assessment
The MMSE was administered to assess cognitive function for each participant. The MMSE consists of 11 simple questions grouped into seven cognitive domains- – orientation to time and place, registration of three words, attention, calculation, recall of three words, language, and visual construction. A possible score of 30 was used to provide a picture of an individual's cognitive performance; a score of <24 indicates cognitive impairment. General clinical parameters such as weight, height, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also determined in the subjects.
Blood sample collection and laboratory analysis
Blood sample was taken at the clinic immediately following the interview with each subject. Serum was extracted and analyzed in the Departments of Human Physiology and Biochemistry, Bayero University, Kano. Determination of BDNF level was done using the BDNF quantikine enzyme-linked immunosorbent assay kit according to the manufacturer's instructions. This was done between the hours of 8 and 10 a.m. to minimize effects of circadian rhythm on BDNF concentrations. This immunoassay system was designed for the sensitive and specific detection of BDNF in an antibody sandwich format. In this format, flat-bottom 96-well plates were coated with anti-BDNF monoclonal antibody to bind soluble BDNF. The captured BDNF binds the second, specific, BDNF polyclonal antibody (pAb). After washing, the amount of specifically bound pAb is detected using a species-specific anti-IgY antibody conjugated to horseradish peroxidase as a tertiary reactant. Unbound conjugate was removed by washing, and following incubation with a chromogenic substrate, the color change was measured. The amount of BDNF in the test solution was proportional to the color generated in the redox reaction.
Data were processed using Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, SPSS Inc., Chicago, IL, USA). All continuous variables were tested for normality using Shapiro–Wilk test. The values of BDNF, age, weight, height, BMI, SPB, and DBP were expressed as mean (±SD) and compared for differences using independent samples t-test, while MMSE score was expressed as median (10th and 90th percentiles) and compared using Mann–Whitney U test. Pearson's moment correlation coefficient or Kendall's tau b was used to determine relationships as appropriate. Statistically significant results were recognized at P < 0.05.
Ethical approval was obtained from the ethical committee of the Kano State Ministry of Health. Signed informed consent was obtained from each participant before commencement of data collection.
| Results|| |
A total of 30 subjects comprising 16 males and 14 females participated in the study. Age, weight, height, BMI, SBP, and BDNF of the subjects were found to be normally distributed (P = 0.178, 0.755, 0.927, 0.595, 0.074, and 0.564, respectively), while MMSE and DBP were observed to be skewed (P = 0.012 and 0.002, respectively).
The mean age of the participants was 48.7 (±11.32) years, while the minimum and maximum ages were 22 and 65 years, respectively. The ages of the male and female participants were similar (t = −1.265, P = 0.216). [Table 1] shows the sociodemographic characteristics of the participants.
The mean systolic and diastolic blood pressures of the participants were 138.67 (±15.25) and 84.00 (±8.60) mmHg, respectively. The participants had a mean weight, height, and BMI of 69.83 (±12.41) kg, 1.58 (±0.06) m, and 27.86 (±4.40), respectively. Male and female participants had statistically similar weight (t = 0.962, P = 0.344), height (t = 0.402, P = 0.691), BMI (t = 0.914, P = 0.369), SBP (t = −0.442, P = 0.662), and DBP (t = 0.253, P = 0.802).
The median MMSE score was 24.00 (21–28) and was not normally distributed [Figure 1], with males and females having statistically similar MMSE score (U = 107, P = 0.833). MMSE score is neither influenced by the sociodemographic characteristics [Table 2] nor anthropometric parameters [Table 3] of the subjects.
|Figure 1: Frequency distribution of Mini Mental State Examination scores of the participants|
Click here to view
|Table 2: Relationship between cognitive score and sociodemographic characteristics of healthy subjects|
Click here to view
|Table 3: Relationship between cognitive score and anthropometric characteristics of healthy subjects|
Click here to view
The mean BDNF level of the subjects was 2.09 ± 0.15 ng/L and was normally distributed [Figure 2] and statistically similar between male and female respondents (t = 1.276, P = 0.213). Serum BDNF level showed moderate positive correlation with language and weak negative correlation with registration as shown in [Table 4].
|Figure 2: Frequency distribution of serum brain-derived neurotrophic factor levels of participants|
Click here to view
|Table 4: Relationship between serum brain-derived neurotrophic factor and cognitive domain scores|
Click here to view
This study observed a significant positive correlation between MMSE score and serum BDNF level (r = 0.369, P = 0.045). MMSE score increases with increasing levels of serum BDNF [Figure 3].
|Figure 3: Variation in cognitive score with peripheral brain-derived neurotrophic factor levels in healthy subjects|
Click here to view
| Discussion|| |
The subjects studied had normal global cognitive function as adjusted by an MMSE score within the normal range. This is in spite of the fact that their cognitive function was significantly correlated with the level of education, which was for the majority of them, not more than sixth grade (primary school). This suggests potential usefulness of the MMSE in assessing cognitive function in this environment. This is so also for the fact that cognition in these subjects was not determined by any of the sociodemographic and anthropometric characteristics examined. These results agree with previous studies that reported no relationship between cognitive function and sociodemographic and anthropometric characteristics.
This study reported serum BDNF level as a normally distributed variable with no sex variation and a moderator of cognitive function in such a way that an increase in BDNF is associated with commensurate increase in cognition in healthy adult subjects. This is encouraging and gives indication that serum BDNF may potentially serve as a biomarker of cognitive function in clinical settings; also given the fact that changes in CNS BDNF levels have been found to parallel that of the periphery as reported by a previous study. BDNF produced by neuronal and non-neuronal tissues such as platelets is broadly expressed in the developing and adult mammalian brain. It crosses the blood–brain barrier to potentiate signal transduction and modulate neuronal plasticity, which forms the basis for learning, memory, and other cognitive functions.
Our results corroborate previous reports where higher serum BDNF levels had been associated with better cognitive function in similar studies among healthy individuals,, as well as studies done by others among subjects with neuropathologic conditions., Details of the relationship from our findings indicate that BDNF is positively correlated with language and negatively correlated with registration domains of cognition, which explains the relatively moderate strength of the overall relationship. This makes serum BDNF a potential index of cognitive function. Our results are consistent with that of Razaei et al. which also reported that stroke survivors with lower levels of BDNF suffered from higher rates of global cognitive impairment, specifically lower scores in domains of memory, registration, and language.
| Conclusion and Recommendation|| |
The findings of this study have led to the conclusion that the population studied had normal cognitive function, which was determined by the level of education and not affected by sociodemographic and anthropometric characteristics. BDNF was a mediator of global cognitive function and was positively associated with registration and negatively associated with language domains of cognition in this population of Africans. Peripheral levels of BDNF may potentially serve as a biomarker and index of cognitive evaluation in clinical settings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ploughman M, Windle V, MacLellan CL, White N, Doré JJ, Corbett D, et al.
Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke 2009;40:1490-5.
Baydyuk M, Xu B. BDNF signaling and survival of striatal neurons. Front Cell Neurosci 2014;8:254.
Gottmann K, Mittmann T, Lessmann V. BDNF signaling in the formation, maturation and plasticity of glutamatergic and GABAergic synapses. Exp Brain Res 2009;199:203-34.
Sasmita AO, Kuruvilla J, Ling APK. Harnessing neuroplasticity: Modern approaches and clinical future. Int J Neurosci 2018;7:1-7.
Pascual-Leone A, Freitas C, Oberman L, Horvath JC, Halko M, Eldaief M, et al.
Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topogr 2011;24:302-15.
Ganguly K, Poo MM. Activity-dependent neural plasticity from bench to bedside. Neuron 2013;80:729-41.
Keller TA, Just MA. Structural and functional neuroplasticity in human learning of spatial routes. Neuroimage 2016;125:256-66.
Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol 2014;220:223-50.
Nys GM, van Zandvoort MJ, Algra A, Kappelle LJ, de Haan EH. Cognitive and functional outcome after intravenous recombinant tissue plasminogen activator treatment in patients with a first symptomatic brain infarct. J Neurol 2006;253:237-41.
Wu MS, Lan TH, Chen CM, Chiu HC, Lan TY. Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan. BMC Public Health 2011;11:22.
Fitzpatrick AL, Kuller LH, Lopez OL, Diehr P, O'Meara ES, Longstreth WT Jr., et al.
Midlife and late-life obesity and the risk of dementia: Cardiovascular health study. Arch Neurol 2009;66:336-42.
Nettiksimmons J, Simonsick EM, Harris T, Satterfield S, Rosano C, Yaffe K, et al.
The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: A longitudinal study. PLoS One 2014;9:e91339.
Béjot Y, Mossiat C, Giroud M, Prigent-Tessier A, Marie C. Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies. PLoS One 2011;6:e29405.
Yu H, Chen ZY. The role of BDNF in depression on the basis of its location in the neural circuitry. Acta Pharmacol Sin 2011;32:3-11.
Leal G, Afonso PM, Salazar IL, Duarte CB. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res 2015;1621:82-101.
Gunstad J, Benitez A, Smith J, Glickman E, Spitznazel M, Alexander T. Serum brain derived neurotrophic factor is associated with cognitive function in healthy older adults. J Geriatr Psychiatry Neurol 2008;90:596-603.
Alfimova MV, Korovaitseva GI, Lezheiko TV, Golimbet VE. Effect of BDNF val66Met polymorphism on normal variability of executive functions. Bull Exp Biol Med 2012;152:606-9.
Tükel R, Gürvit H, Ozata B, Oztürk N, Ertekin BA, Ertekin E, et al.
Brain-derived neurotrophic factor gene val66Met polymorphism and cognitive function in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2012;159B: 850-8.
Razaei S, Asgari-Mobarake K, Keshavarz P, Tolami HF, Soravani MF, Saberi A, et al
. Brain – derived neurotrophic factor (BDNF) Val66met (rs6265) polymorphism associated with global and multidomain cognitive impairment in ischemic stroke patients. Act Neuro Super 2017;59:28-35.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]