Discriminative Analysis of Mild Alzheimer’s Disease and Normal Aging Using Volume of Hippocampal Subfields and Hippocampal Mean Diffusivity

Li, Ya-Di; Dong, Haibo; Xie, Guoming; Zhang, Lingjun

doi:10.1177/1533317513494452

Cited by 44 publications

(57 citation statements)

References 42 publications

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“…In some studies, abnormalities were also found in medial regions of the surface, mostly corresponding to the (pre)subiculum (Frisoni et al, , 2006Wang et al, 2006) or even in all subfields Chow et al, 2012Chow et al, , 2015. Using direct volumetry in AD patients, several studies reported significant atrophy in all, or almost all, investigated subfields (Adachi et al, 2003;Boutet et al, 2014;de Flores et al, 2015;Khan et al, 2014;La Joie et al, 2013;Li et al, 2013), the major atrophy being generally located in CA1 (La Joie et al, 2013;de Flores et al, 2015;Mueller et al, 2010). In a few studies, some subfields were (relatively) spared, namely CA3/DG (Mueller and Weiner, 2009; or CA2 (Wisse et al, 2014b).…”

Section: Subfield Imaging In Admentioning

confidence: 96%

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Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

2015

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Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. The present review provides an overview of the methodological developments that allow the assessment of hippocampal subfield morphology in vivo, and summarizes the results of studies looking at the effects of AD and normal aging on these structures. Most studies highlighted a focal atrophy of the CA1 subfield in the early (predementia or even preclinical) stages of AD, before atrophy becomes more widespread at the dementia stage, consistent with the pathological literature. Preliminary studies have indicated that looking at this focal atrophy pattern rather than standard whole hippocampus volumetry improves diagnostic accuracy at the mild cognitive impairment (MCI) stage. However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques.

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Section: Subfield Imaging In Admentioning

confidence: 96%

“…Thus, all FreeSurfer 5.3 studies have detected volume loss in the subiculum and the CA2/3 region in MCI and AD patients, while only a few articles(Khan et al, 2014;Li et al, 2013) also reported CA1 atrophy (SeeTable 1, bottom section). As mentioned above, this might be due to difference in subfield definition and boundaries used in FreeSurfer 5.3.…”

mentioning

confidence: 94%

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

2015

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“…However, none of these studies assessed the relationship between microstructural damage in the hippocampus and memory performance in aMCI. Numerous studies have also demonstrated that the hippocampal subfields are differentially affected by pathological damage, and DTI parameters may be more sensitive and quantifi able measures of early degeneration in AD than conventional MR imaging techniques [44] .…”

Section: Patientsmentioning

confidence: 99%

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Chen

Zhang

2015

Neurosci. Bull.

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Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). As a part of the medial temporal lobe memory system, the hippocampus is one of the brain regions affected earliest by AD neuropathology, and shows progressive degeneration as aMCI progresses to AD. Currently, no validated biomarkers can precisely predict the conversion from aMCI to AD. Therefore, there is a great need of sensitive tools for the early detection of AD progression. In this review, we summarize the specifi c structural and functional changes in the hippocampus from recent aMCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile, this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of aMCI to AD.

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“…The silent period, if properly detected, would permit the administration of therapies geared to curbing disease progression before the magnitude of nerve tissue damage is too extensive. One of the most commonly used markers to verify disease progression is neuroimaging examination of the hippocampal formation to detect early atrophy in this region (3,5,8,16,20,23,54,63).…”

Section: Introductionmentioning

confidence: 99%

Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome

et al. 2015

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Ribosomes and protein synthesis have been reported to be altered in the cerebral cortex at advanced stages of Alzheimer's disease (AD). Modifications in the hippocampus with disease progression have not been assessed. Sixty-seven cases including middle-aged (MA) and AD stages I-VI were analyzed. Nucleolar chaperones nucleolin, nucleophosmin and nucleoplasmin 3, and upstream binding transcription factor RNA polymerase I gene (UBTF) mRNAs are abnormally regulated and their protein levels reduced in AD. Histone modifications dimethylated histone H3K9 (H3K9me2) and acetylated histone H3K12 (H3K12ac) are decreased in CA1. Nuclear tau declines in CA1 and dentate gyrus (DG), and practically disappears in neurons with neurofibrillary tangles. Subunit 28 ribosomal RNA (28S rRNA) expression is altered in CA1 and DG in AD. Several genes encoding ribosomal proteins are abnormally regulated and protein levels of translation initiation factors eIF2α, eIF3η and eIF5, and elongation factor eEF2, are altered in the CA1 region in AD. These findings show alterations in the protein synthesis machinery in AD involving the nucleolus, nucleus and ribosomes in the hippocampus in AD some of them starting at first stages (I-II) preceding neuron loss. These changes may lie behind reduced numbers of dendritic branches and reduced synapses of CA1 and DG neurons which cause hippocampal atrophy.

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Discriminative Analysis of Mild Alzheimer’s Disease and Normal Aging Using Volume of Hippocampal Subfields and Hippocampal Mean Diffusivity

Abstract: Atrophy was present in almost all hippocampal subfields at mild AD stage. The volumes of CA1 and subiculum were of the most diagnostic significance in discrimination of mild AD, which can be improved by the combination of volume and diffusivity analysis.

Cited by 44 publications

References 42 publications

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome

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