Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 106156

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : December | Volume : 16 | Issue : 12 | Page : CC01 - CC05 Full Version

Cognitive Evoked Potentials in Anaemic Women: A Cross-sectional Study


Published: December 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/58565.17207
Umme Kulsoom Sheema, Alka Rawekar

1. Assistant Professor, Department of Physiology, Mahadevappa Rampure Medical College (RGUHS, Bangalore), Kalaburagi, Karnataka, India. 2. Professor, Department of Physiology, Jawaharlal Nehru Medical College (DMIMS), Nagpur, Maharashtra, India.

Correspondence Address :
Dr. Umme Kulsoom Sheema,
4-601/74/7, Banda Nawaz Colony, MB Nagar Extension, Ring Road, Kalaburagi, Karnataka, India.
E-mail: ummekulsoom22@gmail.com

Abstract

Introduction: Iron Deficiency Anaemia (IDA) is a globally prevalent nutritional disorder and an important risk factor for the development of Mild Cognitive Impairment (MCI). A manifestation of IDA is altered electrogenesis in the central nervous system. As women of reproductive age are more susceptible to this form of anaemia, it is important to assess their cognitive function. Auditory cognitive evoked potentials/P300 are sensitive in detecting MCI which is indicated by prolonged latency and reduced amplitude.

Aim: To investigate the effect of IDA on cognitive function using cognitive evoked potentials/P300 in neurologically intact women.

Materials and Methods: A cross-sectional study was conducted at the Central Neurophysiology Laboratory, Acharya Vinobha Bhave Rural hospital (AVBRH) attached to Jawaharlal Nehru Medical College (JNMC), Wardha, Maharashtra, India, from January 2018 to February 2022. A total of 260 women were recruited for the study. Based on their blood haemoglobin and serum ferritin levels, 130 women were grouped as anaemic and 130 as non anaemic. The P300 was used as an objective tool to assess cognitive function. Haematological parameters like blood haemoglobin and serum ferritin levels were compared (‘t’-test) and correlated (Spearman’s correlation) with the latency and amplitude of the P300 wave in the two groups.

Results: The mean age (years) and Body Mass Index (BMI) (kg/m2) of anaemic women were 23.88±3.67 and 20.98±1.45, respectively; and that of non anaemic women were 24.09±3.41, and 21.25±1.27 (p>0.05) respectively. The blood haemoglobin (mg/dL) and serum ferritin (ng/mL) were significantly (p<0.001) lower in anaemic group (10.37±0.95, 8.55±3.78) compared to non anaemic group (13.02±0.70, 27.61±10.52). The latency of P300 wave (ms) was significantly prolonged (p<0.001) in anaemic women (317.75±7.34) in comparison to non anaemic women (311.71±9.02), while the P300 amplitude did not differ between the two groups (p>0.05). A highly significant low negative correlation of P300 latency with haemoglobin (r=-0.48, p<0.001) and highly significant moderate negative correlation with serum ferritin (r=-0.55, p<0.001) was observed. And a negligible positive correlation of P300 amplitude with haemoglobin (r=0.26, p<0.05) and serum ferritin (r=0.24, p<0.05) was observed.

Conclusion: Cognitive evoked potential is an objective method that aids in the early detection of cognitive impairment. Evaluating the cognitive function in anaemic women and ensuring adequate iron treatment can prevent MCI from progressing to severe forms like dementia and other neuropsychological disorders.

Keywords

Event related potentials, Iron deficiency anaemia, Microcytic hypochromic anaemia, Nutritional anaemia

Anaemia affects approximately one third of the world’s population and the most affected population lies in developing countries. Iron deficiency is the major contributing factor for the development of anaemia. Women in developing countries are more susceptible to this deficiency due to low dietary intake, menstrual blood loss, and increased demand during pregnancy and lactation (1). National Family Health Survey (NFHS)- 5 carried out by the Union Ministry of Health and Family Welfare, India during the year 2019-2021 shows prevalence of anaemia to be 57% in non pregnant women belonging to the age group of 15-49 years (2).

According to WHO, IDA in non pregnant adult females is blood haemoglobin <12 g/dL and serum ferritin <15 ng/mL (1). Iron is required for myelogenesis, synaptogenesis and neurotransmitter synthesis and their regulation in the Central Nervous System (CNS) and hence, its deficiency alters these physiological processes (3). An increase in the severity of ID hampers erythropoiesis leading to iron deficiency anaemia. Reduced haemoglobin levels in IDA are associated with inadequate oxygen supply to the brain. The chronic low oxygen supply may affect the brain energy metabolism, intellectual functioning, and cerebral integrity (4). The IDA has a significant impact on the attention domain of cognition compared to iron deficient and iron replete individuals, aggravating the cognitive dysfunction (5). Evidence from various prospective and cross-sectional studies demonstrated a significant association between anaemia, cognitive decline, and risk of development of dementia (6),(7),(8),(9).

Evoked potentials are electrophysiological signals that are recorded in response to a particular stimulus like a light flash (visual) or a pure tone (auditory) (10). The auditory evoked potential is also known as Cognitive Evoked Potential (CEP) or P300. They are long latency evoked potentials and are helpful to measure the electrophysiological signals that are generated by neuronal activities in multiple regions of the brain. The auditory CEP is an index to measure the attention and working memory domains of cognition (11). P300 was first reported 50 years ago and is recorded as a large positive wave with a peak latency approximately 300 ms after the stimulus onset, therefore, the term P300 (12). The P300 amplitude measures the brain’s processing action to the change in the environmental stimulus. Hence, it is hypothesised as an index of attentional resources and working memory (13). An increase in P300 amplitude reflects increased activation of neural circuits and is proportionate to the attention and memory resources allocated, with larger amplitudes indicating higher cognitive capability (14). It’s latency is related to cognitive efficacy. It is proportional to the time required to detect and evaluate the stimulus and assesses, how rapidly the attentional and memory resources are recruited, indicating the processing time required before a response is generated. While cognitive disorders record prolonged latencies, shorter latencies are related to superior cognitive performance (12).

Systematic review and meta-analysis reported anaemia increases the risk of developing cognitive impairment by 1.39 times and dementia by 34% (15),(16). The CEP evaluation is beneficial in detecting early MCI, assessing the severity of cognitive decline and risk of progression to dementia (17),(18). A clinical trial in anaemic adults observed impaired P300 waves which improved following iron therapy (19). Literature search reveals only few studies utilising these potentials to measure the cognitive function in adult population with IDA (4),(19),(20). As the prevalence of IDA is higher in women, they may be at a greater risk of developing cognitive impairment compared to men. Hence, the present study aimed to investigate whether iron deficiency anaemia impairs the cognitive evoked potentials in neurologically intact women. The objective of the study was, to compare and correlate the cognitive evoked potentials in anaemic and healthy women. Null hypothesis of the study proposes that the cognitive evoked potentials are not altered in women with iron deficiency anaemia.

Material and Methods

The present cross-sectional study was carried out at the Central Neurophysiology Laboratory, Acharya Vinobha Bhave Rural Hospital (AVBRH) attached to Jawaharlal Nehru Medical College (JNMC), Wardha, Maharashtra, India, from January 2018 to February 2022. Women aged 18-30 years from the Department of General Medicine and Obstetrics and Gynaecology, and community volunteers were recruited for the study. Ethical clearance was obtained from the Institutional Ethics Committee, DMIMS (DU) (Reference no. - DMIMS (DU)/IEC/2017-18/6569). An informed consent was taken from the participants before commencing the study.

Sample size calculation: It was calculated as 130 anaemic subjects and 130 non anaemic healthy subjects using the formula “Comparison of means (two groups)” with a Confidence Interval (CI) 95%, power 80% (21).

n≥(Z1-α/2+Z1-β)21222/r)/ (μ12)2

The participants between the age 18-30 years and normal BMI (>18.5 or <23 kg/m2) underwent haematological evaluation for anaemia (22). Participants were grouped as anaemic and non anaemic based on their haemoglobin and serum ferritin levels (1).

Inclusion criteria: For anaemic group (women with IDA)- women whose haemoglobin level was <12 g/dL and serum ferritin <15 ng/mL. For non anaemic group (healthy women without IDA)- women with haemoglobin levels ≥12 g/dL and serum ferritin ≥15 ng/mL.

Exclusion criteria: BMI <18.5 or >23 kg/m2, current pregnancy or pregnancy within the previous year, currently lactating, on hormonal contraceptives, irregular menstrual cycles, recent blood donation, pre-existing ear diseases with clinical deafness, known cases of endocrine disorders (e.g., diabetes mellitus, thyroid dysfunction) and neurological diseases, use of medications-like iron supplements, major or minor tranquilizer that may alter cognitive and neurophysiological measures.

Study Procedure

Blood samples of the enrolled participants were evaluated for a complete haemogram by Coulter and serum ferritin by Electrochemiluminescence Immuno Assay (ECLIA) method according to the “Standard Operating Procedure” (SOP) (23),(24). Based on blood haemoglobin and serum ferritin levels the participants were grouped as women with IDA and healthy women without IDA.

The cognitive evoked potentials/P300 were then recorded using Neurosoft Spectrum-5 (25). The participants were instructed to lie down and close their eyes. Silver disc electrodes were placed at both the mastoids (reference), vertex (active) and forehead (ground) for recording the auditory evoked potentials. The “oddball paradigm” was used to elicit the P300 waves. Each participant was presented with two types of auditory stimuli, such that infrequent target stimuli were given in a background of frequent standard/non target stimuli. Binaural stimuli at 70 dB with target stimuli of 2000 Hz and standard stimuli of 1000 Hz were presented. The participants were instructed to respond by pressing the button to the target stimuli and not to the standard stimuli. A response to the target stimulus elicited a large positive potential with a peak latency at approximately 300 ms, i.e., P300. A total of 100 stimuli were presented and the probability of target stimuli was 30%. Latency (ms) was marked as the time from the stimulus onset to the peak of the positive wave. The amplitude (μV) is measured as a difference between the pre-stimulus baseline and the peak of the positive large wave appearing in a time window of 250-500 ms (26).

Statistical Analysis

Data was analysed using R statistical software (version 4.1.3). The values were expressed as mean and Standard Deviation (SD). The Independent ‘t’-test was applied for comparing the P300 parameters in anaemic and healthy women and the Spearman’s correlation test was applied to find the correlation between haemoglobin and serum ferritin with P300 parameters. A p-value <0.05 was considered statistically significant.

Results

A total of 260 women (130-anaemic, 130-non anaemic) were included in the study, and the mean age of anaemic women was 23.88±3.67 years and 24.09±3.41 years for non anaemic women (p>0.05). Blood haemoglobin levels (mg/dL) were significantly lower in anaemic women (10.37±0.95) than in non anaemic (13.02±0.70) (p <0.001). Serum ferritin (ng/mL) was significantly lower in anaemics (8.55±3.78) compared to non anaemic women (27.61±10.52) (p<0.001) (Table/Fig 1). The P300 wave parameters were compared between the study groups, and it was observed that the P300 latency (ms) was significantly prolonged in anaemic women (317.75±7.34) compared to non anaemic women (311.71±9.02) (p<0.001) (Table/Fig 2),(Table/Fig 3). The P300 amplitude (μV) was reduced in anaemic women compared to non anaemic women, though this difference was not statistically significant (p>0.05) (Table/Fig 2),(Table/Fig 3),(Table/Fig 4).

P300 wave parameters were correlated with haemoglobin and serum ferritin levels (Table/Fig 5). The correlation between P300 latency and haemoglobin was observed as a low negative correlation (r=-0.481, p<0.001) (Table/Fig 6). And the correlation between P300 latency and serum ferritin was a moderate negative correlation (r=-0.552, p<0.001) (Table/Fig 7). The P300 amplitude showed negligible correlation with haemoglobin (r=0.26, p<0.05) (Table/Fig 8) and serum ferritin (r=0.24, p<0.05) (Table/Fig 9).

Discussion

Iron Deficiency Anaemia is a potential risk factor for cognitive decline conceivably due to chronic brain hypo-oxygenation (4). In adulthood, iron is essential for the synthesis of brain neurotransmitters and their regulation (e.g., dopamine, Norepinephrine [NE], serotonin) (3),(27). Inadequate brain iron availability affects neurotransmission and signalling, myelination, neurometabolism, and gene profiles (3),(28). Because of its requirement in the maintenance of these functions, iron deficiency may lead to impaired impulse transmission in the brain (29). Hence, the present study results rejects the null hypothesis that, the cognitive evoked potentials are not altered in women with IDA.

When Electroencephalogram (EEG) signals were correlated with blood haemoglobin and serum ferritin levels, slowed power spectrum in EEG was noted, indicating that systemic iron status affects normal brain functioning (19),(30),(31). The cortical impulses triggered by neurotransmitters released in response to an external stimulus can be recorded non invasively using evoked potentials (11). The auditory evoked potentials like the P300 helps to measure the electrophysiological signals, which are generated by neuronal activities in multiple regions in the brain in response to an auditory stimulus evaluation (10).

The P300 documented in patients with Chronic Kidney Disorders (CKD) after administration of erythropoietin to increase the haematocrit revealed shortened latencies and amplified P300 wave, suggesting that correction of anaemia improves the P300 and hence, neurocognitive functions (32),(33).

Present study findings were consistent with the results from previous studies in adults (4),(19),(20). Khedr et al., observed significantly reduced amplitude and prolonged latencies in anaemics compared to controls. Following iron therapy in cases though amplitudes increased, no change in latencies was observed. The study also found a negative correlation between haemoglobin and P300 latency, and a positive correlation between serum ferritin and amplitude (19). Kececi H and Degirmenci Y also observed improvement in P300 latencies and amplitudes after an improvement in haematological parameters with iron therapy, suggesting that anaemia decreases cognitive performance (4). A case-control study by Kharat P and Waghmare P, in 32 anaemic women and 42 controls showed significantly prolonged latency and reduced amplitude in their cases compared to controls (20).

The hypothesis for neural generators of P300 proposes that during auditory tasks the discrimination between the target and the standard stimuli initiates activity in the frontal lobe which is involved in the attentional function. This is followed by activation of memory operations in the temporoparietal regions, requiring intact integrity at this junctional area. This cascade of activation was evident by neuroimaging techniques like functional Magnetic Resonance Imaging (fMRI) with simultaneous Event Related Potential (ERP) recording revealing frontal to temporoparietal lobe activation (12). According to the dual transmitter P300 hypothesis, the attention domain which is a function of the frontal area is mediated by dopaminergic activity, while the working memory involving the temporoparietal junction is associated with NE activity (13). Rat models indicate that adequate serum iron maintains brain iron (32) and that iron deficiency leads to diminished central dopaminergic transmission and receptor trafficking, with the D2 receptor particularly affected (34),(35),(36). Iron deficiency and hypoxia in IDA are thus implicated in impairing the P300 wave, due to their possible effect on neurotransmitter and brain energy metabolism (14).

As cognition is a fundamental factor for maintaining the quality of life, the impaired cognitive function is correlated with poor quality of life and poor life outlook (37). Anaemic individuals are vulnerable to lack of attentiveness, diminished working memory, delayed decision making, that eventually impairs their cognitive ability (20). Mild cognitive impairment is asymptomatic; however there is a possibility to progress to dementia and Alzheimer’s disease. So, improving the haemoglobin levels with timely treatment has a beneficial effect in reducing the risk of progression to cognitive impairment (38). In future, similar studies reporting the utilisation of P300 for the diagnosis of cognitive impairment in women with anaemia must be encouraged. Further research in a large population, at the community level, for screening cognitive dysfunction using P300 and reporting whether correction of anaemia restores it, is required to support the present findings.

Limitation(s)

Follow-up of anaemic subjects for P300 evaluation after the administration of iron supplements to improve haemoglobin and ferritin levels were not performed. The changes in cognitive evoked potentials post iron supplementation, if at all, will help draw definite conclusions.

Conclusion

Cognitive evoked potential is a sensitive and objective tool for screening cognition. Since anaemia due to iron deficiency impairs these potentials, CEP can be utilised for early detection of MCI associated with IDA. As MCI is a transition phase towards dementia, it is important to screen anaemic women in reproductive age, so as to prevent the clinical and social adverse effects of cognitive decline, in later stages of their life.

References

1.
Nutritional anemia: Tools for effective prevention and control. Geneva: World Health Organization; 2017. https://www.who.int/publications/i/item/9789241513067.
2.
National Family Health Survey (NFHS) 5 (2019 21), National and State Fact Sheets. Available from: http://rchiips.org/nfhs/ factsheet_NFHS 5.shtml. [Last accessed on 2022 Feb 28].
3.
Beard JL, Connar JR. Iron status and neural functioning. Annu Rev Nutr. 2003;23:41-58. [crossref] [PubMed]
4.
Kececi H, Degirmenci Y. Quantitative EEG and cognitive evoked potentials in anemia. Neurophysiol Clin. 2008;38(2):137 43. [crossref] [PubMed]
5.
Cook R, O’ Dwyer N, Parker H, Donges C, Cheng H, Steinbeck K, et al. Iron deficiency anemia, not iron deficiency, is associated with reduced attention in healthy young women. Nutrients. 2017;9(11):1216 28. [crossref] [PubMed]
6.
Atti AR, Palmer K, Volpato S, Zuliani G, Winblad B, Fratiglioni L. Anaemia increases the risk of dementia in cognitively intact elderly. Neurobiol Aging. 2006;27(2):278 84. [crossref] [PubMed]
7.
Shah RC, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Hemoglobin level in older persons and incident alzheimer disease: Prospective cohort analysis. Neurology. 2011;77(33):219 26. [crossref] [PubMed]
8.
Jaleel I, Saikumar P, Devak P. Effect of Hb% on cognitive skills in UG medical students. J Clin Diagn Res. 2013;7(7):1325-27. [crossref] [PubMed]
9.
Agrawal S, Kumar S, Ingole V, Acharya S, Wanjari A, Bawankule S, et al. Does anemia affects cognitive functions in neurologically intact adult patients: Two-year cross-sectional study at rural tertiary care hospital. J Family Med Prim Care. 2019;8(9):3005 8. [crossref] [PubMed]
10.
Vanden Bos, Gary R. Evoked potential. APA Dictionary of Psychology. 2nd ed. Washington, DC: American Psychological Association; 2015. p. 390.
11.
Oken BS. Endogenous event-related potentials. In: Chiappa KH, editor. Evoked Potentials in Clinical Medicine. Philadelphia: JB Lippincott Company; 1999. p. 529-63.
12.
Polich J. Updating P300: An integrative theory of P3a and P3b. Clin Neurophysiol. 2007;118(10):2128 48. [crossref] [PubMed]
13.
Polich J, Criado JR. Neuropsychology and neuropharmacology of P3a and P3b. Int J Psychophysiol. 2006;60(2):172 85. [crossref] [PubMed]
14.
Algarín C, Nelson CA, Peirano P, Westerlund A, Reyes S, Lozoff B. Iron deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. Dev Med Child Neurol. 2013;55(5):453 58. [crossref] [PubMed]
15.
Kung WM, Yuan SP, Lin MS, Wu CC, Islam MM, Atique S, et al. Anemia and the risk of cognitive impairment: An updated systematic review and meta-analysis. Brain Sci. 2021;11(6):777. [crossref] [PubMed]
16.
Gattas BS, Ibetoh CN, Stratulat E, Liu F, Wuni GY, Bahuva R, et al. The impact of low hemoglobin levels on cognitive brain functions. Cureus. 2020;12(11):e11378. [crossref]
17.
Egerházi A, Glaub T, Balla P, Berecz R, Degrell I. P300 in mild cognitive impairment and in dementia. Psychiatr Hung. 2008;23(5):349-57.
18.
Gualbetro Cintra MT, Silva Tavares MC, Gomes SA, de Oliveira Gonçalves T, Mantos da Cunha LC, Gonçalves DU, et al. P300 evoked potential and risk of mild cognitive impairment progression to Alzheimer’s dementia: A literature review. J Neurol Neurophysiol. 2015;6(5):322. [crossref]
19.
Khedr E, Hamed SA, Elbeih E, El Shereef H, Ahmad Y, Ahmed S. Iron states and cognitive abilities in young adults: Neuropsychological and neurophysiological assessment. Eur Arch Psychiatry Clin Neurosci. 2008;258(8):489 96. [crossref] [PubMed]
20.
Kharat P, Waghmare P. Could anemia be the reason for dysfunctional cognition? Int J Res Med Sci. 2015;3(3):663-69. [crossref]
21.
Gupta S, Sharma G, Atri SK, Sharma P. Reversible alteration of brainstem auditory evoked potential in iron deficient anemic patients in response to treatment. Int J Community Med Public Health. 2021;8(4):1877-79. [crossref]
22.
WHO expert consultation appropriate body mass index for Asia populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157-63. [crossref] [PubMed]
23.
Complete Blood Count with 5 Part Differential in Whole Blood NHANES 2013-2014. https://wwwn.cdc.gov/nchs/data/nhanes/2013-2014/labmethods/CBC_H_MET_COMPLETE_BLOOD_COUNT.pdf.
24.
National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Herts, EN6 3QG. http://www.nibsc.ac.uk/documents/ifu/94-572.pdf.
25.
Neuron-Spectrum-5. https://neurosoft.com/en/catalog/eeg/neuron-spectrum-5. [Last accessed on 2022 Sept. 28].
26.
Mishra UK, Kalita J. Clinical neurophysiology: Nerve conduction, electromyography, evoked potentials. 2nd ed. N. Delhi: Reed Elsevier India Private Ltd; 2006. P. 1-9, 329-45, 423-34.
27.
Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133(5 Suppl 1):1468S-72S. [crossref] [PubMed]
28.
Lozoff B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J. Nutr. 2011;141(4):740S-46S. [crossref] [PubMed]
29.
Ferreira A, Neves P, Gozzelino R. Multilevel impacts of iron in the brain: The cross talk between neurophysiological mechanisms, cognition, and social behavior. Pharmaceuticals (Basel). 2019;12(3):126. [crossref] [PubMed]
30.
Wenger MJ, Rhoten SE, Murray-Kolb LE, Scott SP, Boy E, Gahutu JB, et al. Changes in iron status are related to changes in brain activity and behavior in Rwandan female university students: Results from a randomized controlled efficacy trial involving iron biofortified Beans. J Nutr. 2019;149(4):687 97. [crossref] [PubMed]
31.
Otero GA, Aguirre DM, Porcayo R, Fernandez T. Psychological and Electroencephalographic study in school children with iron deficiency. Int J Neurosci. 1999;99(1-4):113 21. [crossref] [PubMed]
32.
Pickett JL, Theberge DC, Brown WS, Schweitzer SU, Nissenson AR. Normalizing hematocrit in dialysis patients improves brain function. Am J Kidney Dis. 1999;33(6):1122 30. [crossref] [PubMed]
33.
Singh NP, Sahni V, Wadhwa A, Garg S, Bajaj SK, Kohli R, et al. Effect of improvement in anemia on electro neurophysiological markers (P300) of cognitive dysfunction in chronic kidney disease. Hemodial Int. 2006;10(3):267-73. [crossref] [PubMed]
34.
Youdim MB, Ben-Shachar D, Yehuda S. Putative biological mechanisms of the effect of iron deficiency on brain biochemistry and behavior. Am J Clin Nutr. 1989;50(3 Suppl):607-15. [crossref] [PubMed]
35.
Erikson KM, Jones BC, Hess EJ, Zhang Q, Beard JL. Iron deficiency decreases dopamine d 1 and d 2 receptors in rat brain. Pharmacol. Biochem Behav. 2001;69(3-4):409-18. [crossref] [PubMed]
36.
Unger EL, Wiesinger JA, Hao L, Beard JL. Dopamine D2 receptor expression is altered by changes in cellular iron levels in PC12 cells and rat brain tissue. J Nutr. 2008;138(12):2487-94. [crossref] [PubMed]
37.
Kwa VIH, Limburg M, de Haan RJ. The role of cognitive impairment in the quality of life after ischaemic stroke. J Neurol. 1996;243(8):599-04. [crossref] [PubMed]
38.
Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia, and Alzheimer’s disease. Nat Rev Neurol. 2018;14(11):653 66. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/58565.17207

Date of Submission: Jun 21, 2022
Date of Peer Review: Aug 06, 2022
Date of Acceptance: Nov 10, 2022
Date of Publishing: Dec 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jun 29, 2022
• Manual Googling: Nov 04, 2022
• iThenticate Software: Nov 09, 2022 (23%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com