Cognitive function in adult NF1 patients without other cognitive disorders: a cross-sectional study

Orphanet J Rare Dis. 2026 Jul 3. doi: 10.1186/s13023-026-04456-6. Online ahead of print.

ABSTRACT

BACKGROUND: Neurofibromatosis type 1 (NF1) is associated with cognitive impairments affecting attention, executive function, memory, visuospatial abilities, and processing speed, which are well described in children and adolescents and may interfere with daily functioning. In contrast, cognitive functioning in adults with NF1 remains less clearly defined, particularly in individuals without previous neurological or psychological conditions affecting cognitive functioning that may confound neuropsychological performance. This cross-sectional study aimed to characterize cognitive performance across multiple domains in adults with NF1 and to examine the relationship between cognitive performance and psychological and clinical variables.

RESULTS: Eighty-seven adults with NF1 and no intellectual disability or previously diagnosed cognitive or psychiatric disorders underwent standardized neuropsychological assessment across seven cognitive domains commonly reported as affected in NF1, particularly in pediatric populations: visual memory, verbal memory, executive function, attention, visuospatial ability, working memory, and visuomotor speed. Participants also completed questionnaires assessing sociodemographic and psychological variables. Cognitive performance was standardized using age-adjusted normative Z-scores. Adults with NF1 performed below the normative mean across several cognitive domains relative to age-adjusted Spanish reference data. Executive function showed clinically significant impairment (z = -2.267), whereas attention showed low-average performance (z = -1.171). Although attention was associated with skin severity and visuospatial ability with depressive symptoms (p < 0.05), these associations were not significant after correction for multiple comparisons.

CONCLUSIONS: These findings suggest a consistent pattern of cognitive underperformance in adults with NF1 without previous neurological or psychological conditions affecting cognitive functioning, supporting the presence of a specific cognitive vulnerability associated with the condition. Although some clinical factors showed associations with specific cognitive domains, these relations were small and did not remain significant after correction for multiple comparisons. These results highlight the importance of routine cognitive assessment and targeted cognitive and psychosocial support strategies, including their integration into genetic counseling, to improve clinical follow-up and patient care.

PMID:42399989 | DOI:10.1186/s13023-026-04456-6