Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders

补充胆碱作为胎儿酒精谱系障碍的神经发育干预措施

• 批准号: 10666452
• 负责人: Michael K. Georgieff
• 金额: $ 59.63万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666452
• 关键词: 10 year old; 5 year old; Acetylcholine; Affect; Age; Attention; Attention deficit hyperactivity disorder; Attenuated; Behavior; Behavior Therapy; Brain; Brain Injuries; Brain imaging; Cells; Child; Child Behavior; Childhood; Choline; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Craniofacial Abnormalities; Custom; Data; Delayed Memory; Development; Developmental Delay Disorders; Diagnostic; Dietary Intervention; Diffusion Magnetic Resonance Imaging; Double-Blind Method; Early treatment; Elements; Epigenetic Process; Episodic memory; Feasibility Studies; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Follow-Up Studies; Future; Gene Expression; Growth; Hippocampus; Human; Impaired cognition; Individual; Intelligence; Intervention; Interview; Left; Long-Term Potentiation; Longitudinal Studies; Longterm Follow-up; Magnetic Resonance Imaging; Maps; Measurable; Measures; Memory; Methods; Methylation; Minnesota; Myelin; Neurocognition; Neurologic; Neurons; Neurotransmitters; Nutrient; Outcome; Parents; Participant; Phase; Placebos; Prefrontal Cortex; Protocols documentation; Public Health; Randomized; Randomized, Controlled Trials; Reporting; Research; Role; Safety; Series; Short-Term Memory; Structure; Supplementation; Symptoms; System; Testing; Thinking; Time; Translating; United States National Institutes of Health; Visuospatial; Work; arm; behavioral impairment; catalyst; choline supplementation; cholinergic; clinical decision-making; clinical implementation; cognitive benefits; cognitive function; cohort; efficacy study; executive function; first-in-human; improved; long term memory; morphometry; neurochemistry; neurodevelopment; neurodevelopmental effect; neuron component; non-verbal; novel; placebo controlled trial; post intervention; postnatal; pre-clinical; processing speed; programs; randomized placebo controlled trial; response; treatment duration; treatment effect; verbal; white matter

PROJECT SUMMARY / ABSTRACT Fetal alcohol spectrum disorders (FASDs) comprise a range of effects resulting from prenatal alcohol exposure (PAE) including neurological abnormalities, cognitive and behavioral impairments, growth retardation, and craniofacial anomalies. Few treatments have been investigated despite FASD’s tremendous public health burden. Cognitive deficits are a core feature of FASD, and cognition is a natural target for intervention. One potential intervention for cognition in FASD is the essential nutrient choline - known to have effects on brain development and cognition. In the hippocampus, choline contributes to increased dendritic arborization, larger cells, and functional changes. Choline affects the cholinergic system and alters brain structure and function in regions essential for memory functioning, including methylation in the hippocampus and prefrontal cortex. Only a handful of human choline studies for FASD have been undertaken and our group has conducted most of them. Our early double-blind, randomized, controlled trial established safety and tolerability. Our subsequent trial revealed beneficial effects for sequential delayed memory in participants with FASD (greater in younger [ages 2-3] rather than older [ages 3-5] children). Our third (ongoing) study included a long- term follow-up that demonstrated long-term benefits for choline vs. placebo in non-verbal processing, working memory, long-term verbal memory, and ADHD behavior. The proposed studies will include a new clinical trial with a new cohort of 2-5 year old children with FASD. Rather than a placebo- controlled trial, it will be a two-arm block-randomized study with cumulative choline exposure durations of 3 or 6 months. Results will directly inform future clinical implementation of choline as a neurodevelopmental intervention. The proposed studies will also capitalize on three existing cohorts for additional longitudinal studies that will determine durability of effects from early treatment. A 4- year and 8-year follow-up study will each examine cognitive effects as well as structural and functional brain effects using advanced MRI methods. Cognitive measures will include the Stanford- Binet Intelligence Scale, the Elicited Imitation memory test, the NIH Toolbox Flanker test and Picture Sequence Memory Test, and the Minnesota Executive Function Scale. We will examine choline effects on behavior using parent-report (CBCL) and a structured diagnostic interview (KSADS). Select hippocampal sub-fields will be examined for volumetric improvements following choline or placebo. Functional connectivity will be examined and is expected to reflect changes from early choline supplementation. We will also use cortical myelin mapping to evaluate choline’s effect on long-term myelin development. In addition, we will apply diffusion-weighted imaging to determine choline’s effect on white matter microstructure – which is known to be disrupted in FASD.

项目摘要/摘要

项目成果

Neurophysiological correlates of memory change in children with fetal alcohol spectrum disorders treated with choline.

• DOI: 10.3389/fpsyg.2022.936019
• 发表时间: 2022
• 期刊: FRONTIERS IN PSYCHOLOGY
• 影响因子: 3.8
• 作者: Fuglestad, Anita J;Miller, Neely C;Fink, Birgit A;Boys, Christopher J;Eckerle, Judith K;Georgieff, Michael K;Wozniak, Jeffrey R
• 通讯作者: Wozniak, Jeffrey R