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Neurodevelopmental Vulnerability in Cognitive Aging: A Dimensional Approach

Siguier, P. L.; Planton, M.; Pages, B.; Wolfrum, M.; Archambault, O.; Damour, A.; Guidolin, V.; Pefferkorn, P.; Danet, L.; Virchien, L.; Magnin, E.; Richard-Mornas, A.; Sauvee, M.; Thomas-Anterion, C.; Mouton, S.; Pariente, J.; Jucla, M.

2026-01-19 neurology
10.64898/2026.01.15.26343771 medRxiv
Show abstract

Neurodevelopmental disorders (NDDs) influence lifespan neurocognitive trajectories and can be conceptualized as falling on a continuum. However, transdiagnostic neurodevelopmental investigations in cognitive aging are rare. This preliminary, cross-sectional study aimed at exploring lifespan manifestations of neurodevelopmental vulnerabilities (DVs) in cognitive aging, while adopting a dimensional approach to NDDs. The objectives, covered from childhood to adulthood, were: 1) to describe NDDs-related domains of vulnerability; 2) to estimate DVs frequency; 3) to evaluate the persistence of DVs symptoms from childhood to adulthood; 4) to explore the link between DVs, demographics and neuropsychological performance. Cognitively healthy participants underwent a neuropsychological assessment and answered a retrospective questionnaire on NDDs symptoms in childhood and in adulthood. Using a k-means clustering based on questionnaire answers, participants were assigned to a DV+ (with DV) or a DV- (without) cluster. The final sample consisted in 84 participants [age: 69 (8); years of education: 14 (3); 57% females]. In childhood, self-management, reading and writing, school performance, and visuospatial difficulties were reported. In adulthood, difficulties were mainly in self-management. Clustering revealed a DV in 15% of individuals during childhood, and in 21% during adulthood. Throughout life, 86% of participants had a consistent cluster assignation, while 13% changed clusters between childhood and adulthood. Childhood self-management and scholar difficulties significantly predicted self-management difficulties in adulthood. Nevertheless, no link was found between DVs, demographics and neuropsychological performance. Results highlight the relevance of lifespan, dimensional investigations of NDDs; and are discussed in terms of cognitive reserve, compensation processes, heterotypic continuity and psychopathological progression. Public Significance StatementThis preliminary study suggests that developmental vulnerabilities can be detected in cognitively healthy aging individuals. Difficulties in their childhood may relate to self-management, reading and writing, school performance, and visuospatial skills; and may predict self-management difficulties in adulthood. HighlightsO_LILifespan neurodevelopmental vulnerabilities (DVs) were screened using a retrospective questionnaire in 84 cognitively healthy older adults. C_LIO_LIA data-driven dimensional analysis identified DVs in 15% of participants during childhood and 18% during adulthood. C_LIO_LIIn childhood, reported difficulties included self-management, reading and writing, school performance, and visuospatial skills. In adulthood, difficulties were mainly in self-management. C_LIO_LIChildhood self-management and scholar difficulties significantly predicted self-management difficulties in adulthood. C_LI

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