Effect of Adherence to a Gluten-Free Diet on Cognitive and Motor Dual-Task Performance in Adolescents Diagnosed With Celiac Disease

Overview

The aim of this cross-sectional observational study is to comprehensively examine the effects of adherence to a gluten-free diet on cognitive, motor, and psychosocial functions in adolescents aged 8-18 years diagnosed with celiac disease. In this context, dual-task gait performance, cognitive processing speed and attention, working memory and executive functions, muscle strength, quality of life, and fatigue levels of individuals with celiac disease who are adherent or non-adherent to a gluten-free diet will be compared with those of healthy peers. In addition, sleep patterns, pubertal development, socioeconomic indicators, and serological markers will be taken into account to evaluate the unique effects of diet adherence on neurocognitive and functional outcomes. All assessments will be conducted in accordance with a predefined standardized protocol. The order of measurement instruments will be randomized to minimize potential bias. Inclusion criteria will consist of being between 8 and 18 years of age, having a celiac disease diagnosis confirmed by serology, being followed with this diagnosis for at least six months, and obtaining written informed consent from both the participant and their parent/guardian. For the healthy control group, participants must be within the same age range and have no history of chronic neurological, psychiatric, or gastroenterological conditions. Data analysis will be performed using SPSS

Detailed description

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten, a protein found in wheat, rye, and barley. With a global prevalence of approximately 1%, it is among the most common autoimmune disorders worldwide. Currently, the only accepted treatment is lifelong adherence to a strict gluten-free diet (GFD). It is now well recognized that CD is associated not only with varying degrees of small intestinal inflammation but also with a wide range of gastrointestinal and extraintestinal manifestations, and it may even be present in asymptomatic individuals. Common extraintestinal manifestations include abnormal liver enzymes, arthralgia/arthritis, alopecia, fatigue, headache, anemia, oral ulcers, myalgia, skin rashes, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. The clinical diagnosis of CD is based on histological evaluation of small intestinal biopsies. Serological tests such as immunoglobulin A (IgA) anti-tissue transglutaminase antibodies and endomysial antibodies (EMA; IgA) may be useful in supporting the diagnosis. Several theories suggest that the globalization and spread of "incorrect" or "excessive" versions of the Mediterranean diet, characterized by very high gluten consumption (up to 20 g/day), may have contributed to the increasing prevalence and incidence of CD. In addition, gluten quality may also play a role. The production of new cereal variants for technological purposes in recent years may have influenced the observed rise in CD diagnoses. Except in regions with low frequencies of CD-predisposing genes and low gluten consumption (such as sub-Saharan Africa and Japan), CD prevalence is higher among first-degree relatives of affected individuals (10-15%) and in other high-risk groups, particularly patients with Down syndrome, type 1 diabetes, or IgA deficiency. In addition to genetic susceptibility and gluten exposure, loss of intestinal barrier function, gluten-triggered proinflammatory innate immune responses, inappropriate adaptive immune responses, and gut microbiome imbalance appear to constitute the fundamental components of CD autoimmunity. An abnormal immune response to gluten in CD classically leads to gastrointestinal symptoms such as abdominal pain, diarrhea, constipation, bloating, and weight loss. CD is now considered a multisystem disorder that affects not only the gastrointestinal tract but also the central nervous system, and has been associated with impairments in attention, short- and long-term memory, and executive function, commonly referred to as "brain fog." Dual-task (DT) gait is thought to involve higher-order cognitive processes that control and regulate behavior, including executive function, gait control, and attentional allocation. This process requires activation of multiple cortical regions, such as the prefrontal cortex (PFC), primary motor cortex, supplementary motor cortex, and somatosensory motor cortex. In addition to cortical activation, network efficiency and functional connectivity among various cortical regions, including the PFC and sensorimotor cortices, have been identified as important contributors to the cortical processes involved in DT gait. The aim of this study is to comprehensively investigate the effects of adherence to a gluten-free diet on cognitive, motor, and psychosocial functions in adolescents aged 8-18 years diagnosed with celiac disease. Accordingly, dual-task gait performance, cognitive processing speed and attentional functions, working memory and executive functions, muscle strength, quality of life, and fatigue levels of GFD-adherent and non-adherent individuals with CD will be compared with those of healthy peers. Furthermore, sleep patterns, pubertal development, socioeconomic indicators, and serological markers will be considered to evaluate the specific effects of dietary adherence on neurocognitive and functional outcomes.

Primary outcome measures

• Dual-task 10-Meter Walk Test [Time frame: baseline one assestmeant]

Secondary outcome measures (9)

• 10-meter walk test [Time frame: Baseline one assestmeant]
• Timed Up And Go [Time frame: Baseline one assestmeant]
• Digit Span Test [Time frame: Baseline one assestmeant]
• Trail Making Test [Time frame: Baseline one assestmeant]
• Tap Fast [Time frame: Baseline one assestmeant]
• The Pediatric Quality of Life Inventory (PedsQL) [Time frame: Baseline one assestmeant]
• The Pediatric Fatigue Scale [Time frame: Baseline one assestmeant]
• The Physical Activity Questionnaire for Children (PAQ-C) The Physical Activity Questionnaire for Adolescents (PAQ-A) [Time frame: Baseline one assestmeant]
• The Pediatric Sleep Questionnaire (PSQ) [Time frame: Baseline one assestmeant]

Eligibility criteria

Inclusion criteria

• Participants aged between 8 and 18 years with a serologically confirmed diagnosis of celiac disease
• Who have been followed for at least six months after diagnosisn
• For whom written informed consent has been obtained from both the participant and their parent/legal guardian, will be included in the study.
• The healthy control group will consist of individuals in the same age range with no history of chronic neurological, psychiatric, or gastroenterological diseases.

Exclusion criteria

• Will include the presence of an acute infection or systemic disease
• Diagnosed neurological disorders (such as epilepsy or cerebral palsy);
• A history of severe psychiatric disorders; conditions that may interfere with test administration, including visual, hearing, or ambulatory impairments
• Initiation of psychotropic medication or changes in the current dosage within the past four weeks; the presence of unstable metabolic or endocrine disorders
• Failure to obtain the required informed consent for participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Other

Study locations

Turkey (Türkiye) · 1 center

• İnönü Üniversitesi Turgut Özal Tıp Merkezi — Malatya

Publications

• Oner P, Barut Y, Oner O, Uneri OS, Bodur S, Turgut S, Munir KM. [Reliability and validity of Turkish translation of the pediatric sleep questionnaire]. Klinik Psikofarmakol Bulteni. 2009;19(4):382-395. Turkish. PMID 28804251
• Janz KF, Lutuchy EM, Wenthe P, Levy SM. Measuring activity in children and adolescents using self-report: PAQ-C and PAQ-A. Med Sci Sports Exerc. 2008 Apr;40(4):767-72. doi: 10.1249/MSS.0b013e3181620ed1. PMID 18317366
• Varni JW, Burwinkle TM, Szer IS. The PedsQL Multidimensional Fatigue Scale in pediatric rheumatology: reliability and validity. J Rheumatol. 2004 Dec;31(12):2494-500. PMID 15570657
• Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001 Aug;39(8):800-12. doi: 10.1097/00005650-200108000-00006. PMID 11468499
• Benton MJ, Spicher JM, Silva-Smith AL. Validity and reliability of handgrip dynamometry in older adults: A comparison of two widely used dynamometers. PLoS One. 2022 Jun 21;17(6):e0270132. doi: 10.1371/journal.pone.0270132. eCollection 2022. PMID 35727792
• Candiri B, Ramazanoglu E, Talu B, Tecellioglu M. The relationship between cognitive function and functional capacity, and cognitive reserve and reaction time in patients with multiple sclerosis. Arq Neuropsiquiatr. 2024 Sep;82(9):1-9. doi: 10.1055/s-0044-1788273. Epub 2024 Aug 26. PMID 39187267
• Şanlı AF, Ersöz Hüseyinsinoğlu B, Bilgiç B, Hanağası HA. Parkinson Hastalarında Algılanan ve Gerçek-Zamanlı Çift-Görev Performansının Farklı Motor-Kognitif Çift-Görev Eşleşmeleri Altında İncelenmesi. Hacettepe University Faculty of Health Sciences Journal. 2025;12(2):516-28.
• Hosoi Y, Kamimoto T, Sakai K, Yamada M, Kawakami M. Estimation of minimal detectable change in the 10-meter walking test for patients with stroke: a study stratified by gait speed. Front Neurol. 2023 Jul 19;14:1219505. doi: 10.3389/fneur.2023.1219505. eCollection 2023. PMID 37538254

Identifiers

NCT: NCT07382999 · 1002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗