Joint Effect of White Matter Lesions and Hippocampal Volumes on Severity of Cognitive Decline: The 3C-Dijon MRI Study

Article type: Research Article

Authors: Godin, Ophélia^{a; b} | Tzourio, Christophe^{a; b} | Rouaud, Olivier^c | Zhu, Yicheng^{a; b; d; e} | Maillard, Pauline^{f; g} | Pasquier, Florence^h | Crivello, Fabrice^{f; g} | Alpérovitch, Annick^{a; b} | Mazoyer, Bernard^{f; g; i; j} | Dufouil, Carole^{a; b; *}

Affiliations: [a] Inserm, U708 “Neuroepidemiology”, Paris, France | [b] Université Pierre et Marie Curie-Paris6, Paris, France | [c] CMRR, Centre Hospitalier de Dijon, Service de Neurologie, Dijon, France | [d] Service de Neurologie, Hopital Lariboisière, Paris, France | [e] Department of Neurology, Peking Union Medical, College Hospital, Beijing, China | [f] CNRS-CEA UMR6194 Groupe d'Imagerie Neurofonctionnelle, Caen, France | [g] Université de Caen Basse-Normande, Caen, France | [h] Departments of Neurology, Lille University Hospital, Lille, France | [i] Centre Hospitalier et Universitaire de Caen, Caen, France | [j] Institut Universitaire de France, Paris, France

Correspondence: [*] Correspondence to: Carole Dufouil, PhD, Inserm Unit 708 "Neuroepidemiology", Hôpital la Salpétrière, 75651 Paris Cédex 13, France. Tel.: +33 142162567; Fax: +33 142162541; E-mail: carole.dufouil@upmc.fr.

Note: [] Handling Associate Editor: Sudha Seshadri

Abstract: Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.

Keywords: Alzheimer's disease, cerebrovascular disease, cohort studies, dementia, risk factors in epidemiology, volumetric MRI

DOI: 10.3233/JAD-2010-1389

Journal: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 453-463, 2010