Modeling the Cognitive Trajectory in CADASIL

Article type: Research Article

Authors: Brice, Sandrine^a | Jabouley, Aude^b | Reyes, Sonia^b | Machado, Carla^b | Rogan, Christina^{b; 1} | Dias-Gastellier, Nathalie^b | Chabriat, Hugues^{b; c} | du Montcel, Sophie Tezenas^{d; *}

Affiliations: [a] Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, Paris, France | [b] Département de Neurologie, Centre de référence CERVCO, Hôpital Lariboisière, AP-HP, Université Paris 7 Denis Diderot, Paris, France | [c] INSERM, Unité Mixte de Recherche 1161, Paris, France | [d] Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Paris, France

Correspondence: [*] Correspondence to: Sophie Tezenas du Montcel, Département d’information médicale (DIM) - GHU APHP Sorbonne Université site Pitié Salpêtrière, 47-83 boulevard de l’Hôpital, 75651 Paris cedex 13, France. Tel.: +33 0 142160582; E-mail: sophie.tezenas@aphp.fr.

Note: [1] Present address: GHU Paris Psychiatrie & Neurosciences, Paris, France.

Abstract: Background:For developing future clinical trials in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), it seems crucial to study the long-term changes of cognition. Objective:We aimed to study the global trajectory of cognition, measured by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS), along the course of CADASIL. Methods:Follow-up data of 185 CADASIL patients, investigated at the French National Referral center CERVCO from 2003, were considered for analysis based on strict inclusion criteria. Assuming that the MMSE and the MDRS provide imprecise measures of cognition, the trajectory of a common cognitive latent process during follow-up was delineated using a multivariate latent process mixed model. After adjustment of this model for sex and education, the sensitivities of the two scales to cognitive change were compared. Results:Analysis of the cognitive trajectory over a time frame of 60 years of age showed a decrease of performances with aging, especially after age of 50 years. This decline was not altered by sex or education but patients who graduated from high school had a higher mean cognitive level at baseline. The sensitivities of MMSE and MDRS scales were similar and the two scales suffered from a ceiling effect and curvilinearity. Conclusion:These data support that cognitive decline is not linear and mainly occurs after the age of 50 years during the course of CADASIL. They also showed that MMSE and MDRS scales are hampered by major limitations for longitudinal studies.

Keywords: Aging, Alzheimer’s disease, behavior, CADASIL, cognitive decline, latent variable modeling, longitudinal studies, neuropsychological tests, patient outcome assessment

DOI: 10.3233/JAD-200310

Journal: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 291-300, 2020