Shared Vulnerability of Two Synaptically-Connected Medial Temporal Lobe Areas to Age and Cognitive Decline: A Seven Tesla Magnetic Resonance Imaging Study
ABSTRACT The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1-SRLM)-two monosynaptically connected structures-exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1-SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1-SRLM and episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1-SRLM share vulnerability to both age and AD-associated atrophy.
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ABSTRACT: In Alzheimer's disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmit-receive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm(3) resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p < 0.05), with average cross-sectional area reductions ranging from -29% to -49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.07/2014; 5. DOI:10.1016/j.nicl.2014.07.011
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ABSTRACT: The hippocampus is one of the most age-sensitive brain regions, yet the mechanisms of hippocampal shrinkage remain unclear. Recent studies suggest that hippocampal subfields are differentially vulnerable to aging and differentially sensitive to vascular risk. Promoters of inflammation are frequently proposed as major contributors to brain aging and vascular disease but their effects on hippocampal subfields are unknown. We examined the associations of hippocampal subfield volumes with age, a vascular risk factor (hypertension), and genetic polymorphisms associated with variation in pro-inflammatory cytokines levels (IL-1β C-511T and IL-6 C-174G) and risk for Alzheimer's disease (APOEε4) in healthy adult volunteers (N = 80; age = 22-82 years). Volumes of three hippocampal subfields, cornu ammonis (CA) 1-2, CA3-dentate gyrus, and the subiculum were manually measured on high-resolution magnetic resonance images. Advanced age was differentially associated with smaller volume of CA1-2, whereas carriers of the T allele of IL-1β C-511T polymorphism had smaller volume of all hippocampal subfields than CC homozygotes did. Neither of the other genetic variants, nor diagnosis of hypertension, was associated with any of the measured volumes. The results support the notion that volumes of age-sensitive brain regions may be affected by pro-inflammatory factors that may be targeted by therapeutic interventions.Brain Structure and Function 06/2014; DOI:10.1007/s00429-014-0817-6 · 4.57 Impact Factor
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ABSTRACT: Growing interest has developed in hippocampal subfield volumetry over the past few years and an increasing number of studies use the automatic segmentation algorithm implemented in FreeSurfer. However, this approach has not been validated on standard resolution T1-weighted magnetic resonance (MR) as used in most studies. We aimed at comparing hippocampal subfield segmentation using FreeSurfer on standard T1-weighted images versus manual delineation on dedicated high-resolution hippocampal scans. Hippocampal subfields were segmented in 133 individuals including 98 cognitively normal controls aged 19-84 years, 17 mild cognitive impairment and 18 Alzheimer's disease (AD) patients using both methods. Intraclass correlation coefficients (ICC) and Bland-Altman plots were computed to assess the consistency between both methods, and the effects of age and diagnosis were assessed from both measures. Low to moderate ICC (0.31-0.74) were found for the subiculum and other subfields as well as for the whole hippocampus, and the correlations were very low for cornu ammonis (CA)1 (<0.1). FreeSurfer CA1 volume estimates were found to be much lower than those obtained from manual segmentation, and this bias was proportional to the volume of this structure so that no effect of age or AD could be detected on FreeSurfer CA1 volumes. This study points to the differences in the anatomic definition of the subfields between FreeSurfer and manual delineation, especially for CA1, and provides clue for improvement of this automatic technique for potential clinical application on standard T1-weighted MR. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.Human Brain Mapping 07/2014; 36(2). DOI:10.1002/hbm.22640 · 6.92 Impact Factor