Neuropsychological profile of prodromal Lewy bodies disease. Preliminary results

Aim: The prodromal stage of dementia with Lewy bodies (pro-DLB) has been recently defined by Mckeith’s and colleagues in research context [1]. However, the neuropsychological profile of these patients, especially in relation to their clinical onset (i.e., mild cognitive impairment [MCI], psychiatric-onset, or delirium-onset), has not yet been thoroughly investigated. This study aimed to clarify the neuropsychological markers of pro-DLB. Materials: We included patients with pro-DLB (20 MCI-DLB, 13 psychiatric-onset) and 18 with MCI due to Alzheimer’s disease (AD). All patients underwent an extensive neuropsychological battery assessing all cognitive domains and neuropsychiatric symptoms. Qualitative neuropsychological indices for principal neurocognitive deficit observed in DLB patients [2] were developed to capture subtle differences in pro-DLB. Methods: A one-way ANOVA was performed to compare groups’ demographics and clinical scores as well as performances on neuropsychological tests and neuropsychiatric questionnaires. Result: Pro-DLB patients showed worst performance in computerized tests of alertness and working memory, in visuo-perceptive, visuo-spatial and visuo-constructive processing. In detail, MCI-LB obtained lower score in visuo-spatial, visuo-perceptive and computerized working-memory task; a trend towards significance emerged in visuo-constructive test. Using computerized test of alertness, both MCI-LB and psychiatric-onset patients showed a trend towards significance with worse performance than MCI-AD. Interesting, although MCI-LB had a more severe cognitive profile, no relevant difference emerged between MCI-LB and psychiatric group. As expected, in comparison to MCI-AD, pro-DLB patients showed a better performance in verbal memory tasks. Qualitative neuropsychological analysis indicated that MCI-LB committed more visuo-spatial errors than MCI-AD but Psychiatric patients too. Regarding neuropsychiatric symptoms, MCI-LB patients had greater anxiety, more severe and frequent hallucinations and sleep disorders rather than MCI-AD but not compared to psychiatric group. Discussion: In line with the full-blown disease, the neuropsychological profile of pro-DLB patients is characterized by deficits in visuo-perceptive, visuo-spatial and visuo-constructive abilities as well as attention. Notably, these results reflect the presence of major visuospatial deficits and attentional fluctuations symptoms both in MCI-LB and in psychiatric-onset. Conclusion: Test assessing attention, visuo-perceptual abilities and working memory are helpful in differentiating pro-DLB compared to MCI-AD. The lack of significative differences between MCI-LB and psychiatric group, suggest a neuropsychological and neuropsychiatric similarity of these phenotypes defined as pro-DLB in McKeith's criteria. Moreover, the use of computerized tasks and qualitative indices could improve the neuropsychological assessment accuracy of prodromal DLB patients. These findings may represent an initial step toward developing a neuropsychological battery specifically tailored to prodromal DLB. References: 1McKeith, I. G., Ferman, T. J., Thomas, A. J., Blanc, F., Boeve, B. F., Fujishiro, H., ... & prodromal DLB Diagnostic Study Group. (2020). Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology, 94(17), 743-755. 2 Wyman-Chick KA, Bayram E, Gravett S, et al. Neuropsychological test performance in mild cognitive impairment with Lewy bodies: A system- atic review and meta-analysis. Alzheimer’s Dement. 2025;1-20