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

Autoři: Thomas D. Parker aff001;  David M. Cash aff001;  Christopher A. S. Lane aff001;  Kirsty Lu aff001;  Ian B. Malone aff001;  Jennifer M. Nicholas aff001;  Sarah-Naomi James aff003;  Ashvini Keshavan aff001;  Heidi Murray-Smith aff001;  Andrew Wong aff003;  Sarah M. Buchanan aff001;  Sarah E. Keuss aff001;  Carole H. Sudre aff001;  Marc Modat aff001;  David L. Thomas aff006;  Sebastian J. Crutch aff001;  Marcus Richards aff003;  Nick C. Fox aff001;  Jonathan M. Schott aff001
Působiště autorů: The Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, United Kingdom aff001;  Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom aff002;  MRC Unit for Lifelong Health and Ageing at University College London, London, United Kingdom aff003;  School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom aff004;  Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom aff005;  Leonard Wolfson Experimental Neurology Centre, Queen Square Institute of Neurology, University College London, London, United Kingdom aff006;  Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, Queen Square Institute of Neurology, University College London, London, United Kingdom aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224030



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.


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.


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.


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.

Klíčová slova:

Alzheimer's disease – Central nervous system – Cognitive impairment – Dentate gyrus – Elderly – Magnetic resonance imaging – Memory recall – Positron emission tomography


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