Automated Hippocampal Subfield Volumetric Analyses in Atypical Alzheimer’s Disease

Article type: Research Article

Authors: Gabere, Musa^a | Thu Pham, Nha Trang^b | Graff-Radford, Jonathan^a | Machulda, Mary M.^c | Duffy, Joseph R.^a | Josephs, Keith A.^a | Whitwell, Jennifer L.^{b; *} | for Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [b] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [c] Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

Correspondence: [*] Correspondence to: Jennifer L. Whitwell, PhD, Professor of Radiology, Mayo Clinic, 200 1st St SW, Rochester MN 55905, USA. Tel.: +1 507 284 4476; Fax: +1 507 284 9778; E-mail: whitwell.Jennifer@mayo.edu

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are two of the most common variants of atypical Alzheimer’s disease (AD). Both PCA and LPA are associated with relative sparing of hippocampus compared to neocortex, although hippocampal atrophy is observed. It is unclear whether regional patterns of hippocampal subfield involvement differ between PCA and LPA, and whether they differ from typical AD. Objective:To assess volume of specific subfields of the hippocampus in PCA, LPA, and typical AD. Methods:Fifty-nine patients with PCA and 77 patients with LPA were recruited and underwent T1-weighted MRI and Pittsburgh Compound B (PiB) PET at Mayo Clinic. Thirty-six probable AD patients and 100 controls were identified from the Alzheimer’s Disease Neuroimaging Initiative. Hippocampal subfield volumes were calculated using Freesurfer, and volumes were compared between PCA, LPA, AD, and controls using Kruskal-Wallis and Dunn tests. Results:The LPA and PCA groups both showed the most striking abnormalities in CA4, presubiculum, molecular layer of the hippocampus, molecular and granule cell layers of the dentate gyrus, and the hippocampal-amygdala transition area, although atrophy was left-sided in LPA. PCA showed smaller volume of right presubiculum compared to LPA, with trends for smaller volumes of right parasubiculum and fimbria. LPA showed a trend for smaller volumes of left CA1 compared to PCA. The AD group showed smaller volumes of the right subiculum, CA1, and presubiculum compared to LPA. Conclusion:Patterns of hippocampal subfield atrophy differ across the different syndromic variants of AD.

Keywords: Alzheimer’s disease, hippocampal subfields, hippocampus, logopenic progressive aphasia, magnetic resonance imaging, posterior cortical atrophy

DOI: 10.3233/JAD-200625

Journal: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 927-937, 2020