# The Real-World Early Neuroprotective Effects of Oral Citicoline Combination in Prodromal Dementia

**Authors:** Aynur Özge, Ayhan Bingöl, Sevim Eyüboğlu, Ayşe İrem Can, Bahar Taşdelen, Ezgi Uluduz, Derya Uludüz

PMC · DOI: 10.3390/nu18040595 · Nutrients · 2026-02-11

## TL;DR

This study found that an oral citicoline combination improved cognitive and mood outcomes in people with early dementia signs, but more research is needed.

## Contribution

The study provides real-world evidence of citicoline's multidomain cognitive and mood benefits in prodromal dementia.

## Key findings

- Citicoline improved executive functions, processing speed, and memory domains in early dementia patients.
- Participants showed better mood outcomes with reduced depressive and anxiety symptoms.
- Lower-educated individuals had greater cognitive gains from citicoline use.

## Abstract

Background/Objectives: Early intervention in the prodromal stages of dementia is a primary focus of contemporary research, as delaying clinical progression may have a substantial public health impact. Citicoline, an endogenous precursor of phosphatidylcholine and acetylcholine, has been proposed as a nutritional compound with potential relevance to multiple cognitive domains. However, real-world evidence regarding its specific contributions in prodromal dementia populations is limited. This study was conducted to examine cognitive, functional, and emotional outcomes associated with the use of an oral citicoline combined preparation in individuals with prodromal dementia and early Alzheimer’s type cognitive decline. Methods: This was a two-centre, retrospective, observational, real-world cohort study. A cohort of 100 patients receiving a combined oral citicoline preparation and 50 age-matched healthy controls were evaluated at baseline and followed for 6–9 months. Participants underwent comprehensive neuropsychological assessments that evaluated domains including executive function, attention, processing speed, working memory, visual-spatial and verbal memory, fluency, general cognition, and mood. Standardized instruments included Stroop indices, Trail Making Tests A/B, SDMT, SPART-based measures, SBST, fluency tasks, the Boston Naming Test, and MoCA. Statistical analyses included age-adjusted and education-level-stratified comparisons. Results: Use of the citicoline combined preparation was associated with improvements in several cognitive domains, including executive functions, processing speed, working memory, visual-spatial memory, and both semantic and episodic fluency (all p < 0.05). Functional memory scanning and global cognition also showed improvement over the observation period. Significant differences between groups were observed at baseline and follow-up for multiple cognitive indices (most p < 0.001). Mood outcomes were more favorable in the citicoline combined preparation group, with reductions in depressive and anxiety symptoms. Age-adjusted models identified age as an important covariate, and participants with lower educational levels demonstrated comparatively greater cognitive gains. Conclusions: In this real-world observational study, use of an oral citicoline combined preparation was associated with multidomain improvements in cognitive and mood-related outcomes in individuals with prodromal dementia/early Alzheimer-type decline. Given the observational design, these findings should be considered exploratory and require confirmation in prospective randomised controlled trials.

## Linked entities

- **Chemicals:** citicoline (PubChem CID 13804)
- **Diseases:** dementia (MONDO:0001627)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}
- **Diseases:** anxiety symptoms (MESH:D001008), Alzheimer's type cognitive decline (MESH:D003072), memory impairment (MESH:D008569), Prodromal Dementia (MESH:D062706), Hearing impairment (MESH:D034381), synaptic dysfunction (MESH:C536122), type (MESH:D006969), dementia (MESH:D003704), white matter hyperintensities (MESH:D056784), type 2 diabetes (MESH:D003924), Depression (MESH:D003866), obesity (MESH:D009765), obsessive-compulsive disorder (MESH:D009771), insulin resistance (MESH:D007333), Anxiety (MESH:D001007), atrophy (MESH:D001284), schizophrenia (MESH:D012559), SCD (MESH:C536778), neurocognitive disorders (MESH:D019965), neurological or psychiatric disease (MESH:D001523), Alzheimer (MESH:D000544), MCI (MESH:D060825), sensory deficits (MESH:D012678), vascular dementia (MESH:D015140), Hypertension (MESH:D006973), gastrointestinal malabsorption syndromes (MESH:D008286), inflammatory (MESH:D007249), injury to (MESH:D014947), neurodegeneration (MESH:D019636), cerebral hypometabolism (MESH:D002547)
- **Chemicals:** UMP (MESH:D014542), cytidine (MESH:D003562), lipid (MESH:D008055), acetylcholine (MESH:D000109), phospholipid (MESH:D010743), FDG (MESH:D019788), phosphatidylcholine (MESH:D010713), Phosphatidylserine (MESH:D010718), homocysteine (MESH:D006710), choline (MESH:D002794), PS (MESH:D010758), CDP-choline (MESH:D003566), B1, B2, B6, B12 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942905/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942905/full.md

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Source: https://tomesphere.com/paper/PMC12942905