# Association of spinal cord structure with cognition in hereditary spastic paraplegia type 5

**Authors:** Xuanyu Chen, Kunxin Lin, Liangliang Qiu, Ruying Yuan, Yusen Qiu, Jin Bi, Zhixian Ye, Wanjin Chen, Ning Wang, Ying Fu

PMC · DOI: 10.3389/fneur.2025.1639011 · Frontiers in Neurology · 2026-01-02

## TL;DR

This study finds that spinal cord atrophy in a genetic disorder is linked to cognitive impairments, particularly in memory and processing speed.

## Contribution

The novel contribution is establishing a direct link between spinal cord structure and cognitive function in hereditary spastic paraplegia type 5.

## Key findings

- SPG5 patients showed significant cognitive deficits in visuospatial perception, executive function, and processing speed.
- Thoracic spinal cord measurements correlated with visual memory and global cognition scores.
- Spinal cord atrophy in SPG5 was significantly reduced compared to healthy controls.

## Abstract

Cognitive deficits often accompany brain structural changes, but the association between spinal cord atrophy and cognitive function remains unclear. Spastic paraplegia type 5 (SPG5) is a subtype of hereditary spastic paraplegias (HSPs), caused by mutations in cholesterol metabolism genes, with radiological features of spinal cord atrophy. Our study aims to explore cognitive impairment in SPG5 and its relation to spinal cord structure.

We conducted a prospective cross-sectional study with 30 HSPs patients and 47 healthy controls (HC), performing brain and spinal cord MRI and neuropsychological assessments. We investigated correlations between cognitive performance and MRI measurements.

Compared to HC, SPG5 patients exhibited significant impairments in the Benton Judgment of Line Orientation Test (p = 0.033), Controlled Oral Word Association Test (p = 0.028), and Symbol Digit Modalities Test (p = 0.023). SPG5 patients also demonstrated significant reductions in spinal cord and thoracic cord cross-sectional area (CSA), anterior-posterior (AP) diameter, and right-left (RL) total (All p < 0.01). Specifically, the thoracic cord RL total was positively correlated with scores on the Brief Visuospatial Memory Test - Revisited delayed recall (BVMT-R DR) and Montreal Cognitive Assessment (MoCA). The spinal cord RL total explained 81% of the variance in BVMT-R DR (p = 0.015) and 74% of the variance in MoCA (p = 0.027).

SPG5 patients demonstrate deficits in visuospatial perception, executive function, and information processing speed. Thoracic spinal cord RL total was positively associated with visual memory and global cognition.

## Full-text entities

- **Diseases:** Cognitive deficits (MESH:D003072), spinal cord atrophy (MESH:D013118), HSPs (MESH:D015419)
- **Chemicals:** cholesterol (MESH:D002784)
- **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/PMC12807918/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12807918/full.md

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Source: https://tomesphere.com/paper/PMC12807918