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. 2019 Oct 17;14(10):e0224030.
doi: 10.1371/journal.pone.0224030. eCollection 2019.

Hippocampal subfield volumes and pre-clinical Alzheimer's disease in 408 cognitively normal adults born in 1946

Thomas D Parker  1 , David M Cash  1 , Christopher A S Lane  1 , Kirsty Lu  1 , Ian B Malone  1 , Jennifer M Nicholas  1   2 , Sarah-Naomi James  3 , Ashvini Keshavan  1 , Heidi Murray-Smith  1 , Andrew Wong  3 , Sarah M Buchanan  1 , Sarah E Keuss  1 , Carole H Sudre  1   4   5 , Marc Modat  1   4   5 , David L Thomas  6   7 , Sebastian J Crutch  1 , Marcus Richards  3 , Nick C Fox  1 , Jonathan M Schott  1
Affiliations

Hippocampal subfield volumes and pre-clinical Alzheimer's disease in 408 cognitively normal adults born in 1946

Thomas D Parker et al. PLoS One. .

Abstract

Background: The human hippocampus comprises a number of interconnected histologically and functionally distinct subfields, which may be differentially influenced by cerebral pathology. Automated techniques are now available that estimate hippocampal subfield volumes using in vivo structural MRI data. To date, research investigating the influence of cerebral β-amyloid deposition-one of the earliest hypothesised changes in the pathophysiological continuum of Alzheimer's disease-on hippocampal subfield volumes in cognitively normal older individuals, has been limited.

Methods: Using cross-sectional data from 408 cognitively normal individuals born in mainland Britain (age range at time of assessment = 69.2-71.9 years) who underwent cognitive assessment, 18F-Florbetapir PET and structural MRI on the same 3 Tesla PET/MR unit (spatial resolution 1.1 x 1.1 x 1.1. mm), we investigated the influences of β-amyloid status, age at scan, and global white matter hyperintensity volume on: CA1, CA2/3, CA4, dentate gyrus, presubiculum and subiculum volumes, adjusting for sex and total intracranial volume.

Results: Compared to β-amyloid negative participants (n = 334), β-amyloid positive participants (n = 74) had lower volume of the presubiculum (3.4% smaller, p = 0.012). Despite an age range at scanning of just 2.7 years, older age at time of scanning was associated with lower CA1 (p = 0.007), CA4 (p = 0.004), dentate gyrus (p = 0.002), and subiculum (p = 0.035) volumes. There was no evidence that white matter hyperintensity volume was associated with any subfield volumes.

Conclusion: These data provide evidence of differential associations in cognitively normal older adults between hippocampal subfield volumes and β-amyloid deposition and, increasing age at time of scan. The relatively selective effect of lower presubiculum volume in the β-amyloid positive group potentially suggest that the presubiculum may be an area of early and relatively specific volume loss in the pathophysiological continuum of Alzheimer's disease. Future work using higher resolution imaging will be key to exploring these findings further.

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Conflict of interest statement

NCF’s research group has received payment for consultancy or for conducting studies from Biogen, Eli Lilly Research Laboratories, GE Healthcare, and Roche. NCF receives no personal compensation for the activities mentioned above. JMS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), has consulted for Roche Pharmaceuticals, Biogen, Merck and Eli Lilly, given educational lectures sponsored by GE Healthcare, Eli Lilly and Biogen, and serves on a Data Safety Monitoring Committee for Axon Neuroscience SE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Age is associated with lower CA1 (panel A), CA4 (panel B), dentate gyrus (panel C) and subiculum (panel D) volume in cognitively normal older adults following adjustment for sex, TIV, amyloid status and WMHV. Dashed lines represent 95% confidence intervals, TIV = total intracranial volume; WMHV = white matter hyperintensity volume.
See this image and copyright information in PMC

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