Temporal Cortical Thickness and Cognitive Associations among Typical and Atypical Phenotypes of Alzheimer's Disease.

Background

The hippocampus and temporal lobe are atrophic in typical amnestic Alzheimer's disease (tAD) and are used as imaging biomarkers in treatment trials. However, a better understanding of how temporal structures differ across atypical AD phenotypes and relate to cognition is needed.

Objective

Our goal was to compare temporal lobe regions between tAD and two atypical AD phenotypes (logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA)), and assess cognitive associations.

Methods

We age and gender-matched 77 tAD participants to 50 LPA and 27 PCA participants, all of which were amyloid-positive. We used linear mixed-effects models to compare FreeSurfer-derived hippocampal volumes and cortical thickness of entorhinal, inferior and middle temporal, and fusiform gyri, and to assess relationships between imaging and memory, naming, and visuospatial function across and within AD phenotype.

Results

Hippocampal volume and entorhinal thickness were smaller bilaterally in tAD than LPA and PCA. PCA showed greater right inferior temporal and bilateral fusiform thinning and LPA showed greater left middle and inferior temporal and left fusiform thinning. Atypical AD phenotypes differed with greater right hemisphere thinning in PCA and greater left hemisphere thinning in LPA. Verbal and visual memory related most strongly to hippocampal volume; naming related to left temporal thickness; and visuospatial related to bilateral fusiform thickness. Fewer associations remained when examined within AD group.

Conclusion

Atypical AD phenotypes are associated with greater thinning of lateral temporal structures, with relative sparing of medial temporal lobe, compared to tAD. These findings may have implications for future clinical trials in AD.

Informations de copyright

© 2022 – The authors. Published by IOS Press.

Déclaration de conflit d'intérêts

Drs. Machulda, Josephs, Whitwell, and Duffy receive funding from the NIH. Dr. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). Dr. Graff-Radford is funded by the NIH and serves on the Neurology editorial board. Dr. Jack serves on an independent data monitoring board for Roche, has served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. Dr. Knopman serves on a Data Safety Monitoring Board for the DIAN study. He serves on a Data Safety monitoring Board for a tau therapeutic for Biogen but receives no personal compensation. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Third Rock and Alzeca Biosciences but receives no personal compensation. He receives funding from the NIH. The remaining authors have no conflict of interest to report.