Reduced Gray Matter Volume of the Thalamus and Hippocampal Region in Elderly Healthy Adults with no Impact of APOE ɛ4: A Longitudinal Voxel-Based Morphometry Study

Article type: Research Article

Authors: Squarzoni, Paula^{a; b} | Duran, Fabio Luis Souza^{a; b} | Busatto, Geraldo F.^{a; b} | Alves, Tania Correa Toledo de Ferraz^{a; b; *}

Affiliations: [a] Department of Psychiatry, Laboratory of Psychiatric Neuroimaging (LIM 21), Faculty of Medicine, University of São Paulo, São Paulo, Brazil | [b] Núcleo de Apoio à Pesquisa em Neurociência Aplicada (NAPNA), University of São Paulo, São Paulo, Brazil

Correspondence: [*] Correspondence to: Tania Correa Toledo de Ferraz Alves, MD, PhD, Centro de Medicina Nuclear, 2° andar, LIM-21, Rua Dr. Ovídio Pires Campos 872, postal code 05403–010, São Paulo – SP, Brazil. E-mail: [email protected].

Abstract: Background:Many cross-sectional voxel-based morphometry (VBM) investigations have shown significant inverse correlations between chronological age and gray matter (GM) volume in several brain regions in healthy humans. However, few VBM studies have documented GM decrements in the healthy elderly with repeated MRI measurements obtained in the same subjects. Also, the extent to which the APOE ɛ4 allele influences longitudinal findings of GM reduction in the healthy elderly is unclear. Objective:Verify whether regional GM changes are associated with significant decrements in cognitive performance taking in account the presence of the APOE ɛ4 allele. Methods:Using structural MRI datasets acquired in 55 cognitively intact elderly subjects at two time-points separated by approximately three years, we searched for voxels showing significant GM reductions taking into account differences in APOE genotype. Results:We found global GM reductions as well as regional GM decrements in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE ɛ4. Conclusions:Irrespective of APOE ɛ4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is greater than the degree of global volume reduction in healthy elderly subjects.

Keywords: Aging, APOE4, cardiovascular risk, cognition, longitudinal study, magnetic resonance imaging

DOI: 10.3233/JAD-161036

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 757-771, 2018