AUTHOR=Rane Levendovszky Swati 

TITLE=Cross-Sectional and Longitudinal Hippocampal Atrophy, Not Cortical Thinning, Occurs in Amyloid-Negative, p-Tau-Positive, Older Adults With Non-Amyloid Pathology and Mild Cognitive Impairment

JOURNAL=Frontiers in Neuroimaging

VOLUME=Volume 1 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroimaging/articles/10.3389/fnimg.2022.828767

DOI=10.3389/fnimg.2022.828767

ISSN=2813-1193

ABSTRACT=INTRODUCTION: Alzheimer’s disease (AD) is a degenerative disease characterized by pathological accumulation of amyloid and phosphorylated tau. Typically, the early stage of AD, also called mild cognitive impairment (MCI) shows amyloid pathology. A small but significant number of MCI individuals do not exhibit amyloid pathology but have elevated phosphorylated tau level (A-T+ MCI). We used CSF amyloid and phosphorylated tau to identify these A+T+ and A-T+ MCI individuals as well as cognitively normal (A-T-) controls. To increase sample size, we leveraged the Global Alzheimer's Association Interactive Network and identified 137MCI+ and 61 A-T+ MCI participants. We compared baseline and longitudinal, hippocampal, and cortical atrophy between groups.
METHODS: We applied ComBat harmonization to minimize site-related variability and used FreeSurfer for all measurements.
RESULTS: Harmonization reduced unwanted variability in cortical thickness by 3.4% and in hippocampal volume measurement by 10.3%. Cross-sectionally, widespread cortical thinning with age was seen in the A+T+ and A-T+ MCI groups (p<0.0005). Decrease in hippocampal volume with age was faster in both groups (p<0.05) than in controls. Longitudinally also, hippocampal atrophy rates were significant (p<0.05) when compared to controls. No longitudinal cortical thinning was observed in A-T+ MCI group.
DISCUSSION: A-T+ MCI participants showed similar baseline cortical thickness patterns with aging and longitudinal hippocampal atrophy rates as A+T+ MCI participants but no longitudinal cortical atrophy signature.