Differential correlation of amyloid binding with hippocampal subfield volume loss in cognitively normal participants

Yvette I. Sheline, Koen Van Leemput, Daniel S. Marcus, Tammie Benzinger, Bruce Fischl, John Carl Morris

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Background
Pathological examination has suggested early involvement of CA1 and CA2 in hippocampal cell loss and manual tracing in amnestic MCI has found volume loss at the CA1-CA2 boundary. With the recent development and validation of hippocampus subfield segmentation it is now possible to reliably analyze changes across populations and correlations with other biomarkers. Increased cortical amyloid binding is among the earliest changes in preclinical AD, preceding overall hippocampal atrophy. In this investigation we sought to determine whether hippocampal CA1 and CA2 subfield volume loss correlated with mean amyloid cortical binding potential (MCBP).

Methods
Cognitively normal participants (n = 46; 34 females (74%) were assessed with the clinical dementia rating (CDR) scale = 0 at the Washington University ADRC. Mean and (SD) for age and education were 63.8 (7.6) and 16.1 (2.6) respectively. MRI was perfomed on a 3T Siemens Trio system with 12-channel head coil; voxel size = 1x1x1 mm obtained sagitally; Hippocampal subfield segmentation used Freesurfer pipeline (Martinos Center http://surfer.nmr.mgh.harvard.edu/) yielding 7 segments for both left and right hippocampus: CA1, CA2-3, CA4-DG, subiculum, presubiculum, fimbria and hippocampal fissure. Amyloid-β PET imaging was conducted following ≈ 12 mCi of [11C] PIB and 60 min dynamic PET scan in 3D mode (septa retracted). Mean cortical binding potential (MCBP) was determined as previously described.

Results
Pearson correlation revealed the following correlations and trends between MCBP (for amyloid) and hippocampal subvolumes: left CA2-3 r = -0.29 (P = 0.05); right CA2-3 r = -0.25 (P = 0.09); left CA1 r = -0.20 (P = 0.18); right CA1 r = -0.27 (P = 0.07). No other regional volumes were correlated with MCBP.

Conclusions
In this young healthy cognitively normal population there were trends towards the same pattern seen recently in an amnestic MCI population, with significantly smaller subfield volumes in CA 2-3 and subiculum compared with controls. In our study group only 8/46 participants had elevated MCBP (> 0.18 BP). We will extend our sample to a larger and older population, which can be expected to have higher numbers of participants with elevated amyloid.
Original languageEnglish
JournalAlzheimer's & Dementia
Volume8
Issue number4, Supplement
Pages (from-to)P4–P5
ISSN1552-5260
DOIs
Publication statusPublished - 2012
Externally publishedYes
EventAlzheimer's Association International Conference (AAIC 2012) - Boston, United States
Duration: 13 Jul 201218 Jul 2012

Conference

ConferenceAlzheimer's Association International Conference (AAIC 2012)
CountryUnited States
CityBoston
Period13/07/201218/07/2012

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