The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are ...most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18–95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3 voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3 voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 × 0.4 × 2 mm3 voxels) images were included. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.
The apolipoprotein E ε4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of ...symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD. We analyzed the effect of an APOE4 allele on cognitive measures, volumetric MRI, amyloid deposition, glucose metabolism, and on cerebrospinal fluid levels of AD biomarkers in 162 participants that did not carry the mutant gene (noncarriers). APOE4+ and APOE4− mutation noncarriers had similar performance on cognitive measures. Amyloid deposition began at an earlier age in APOE4+ participants, whereas hippocampal volume was similar between the groups. These preliminary findings are consistent with growing evidence that the APOE4 allele may exert effects in midlife years before symptom onset, promoting amyloid deposition before altering cognitive performance or brain structure.
•A single APOE4 allele does not affect cognitive measures in people aged 19–69 years.•A single APOE4 allele does not affect structural or imaging measures in people aged 19–69 years.•An APOE4 allele does affect amyloid deposition with age in people aged 19–69 years.•An APOE4 allele may accelerate amyloid deposition, possibly beginning as early as the 30–40 years of age.
Statistical effects of cortical metrics derived from standard T1‐ and T2‐weighted magnetic resonance imaging (MRI) images, such as gray–white matter contrast (GWC), boundary sharpness coefficient ...(BSC), T1‐weighted/T2‐weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between‐marker age‐related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo‐ and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18–81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression‐derived cell‐type densities, histology‐derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between‐marker age‐related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.
Cortical MRI markers and their statistical effects are often thought to be driven by intracortical myelin. We report higher spatial relations of these markers with indicators of myelin and glial cells compared to neuronal cells. Comparing markers between themselves, we show generally high spatial overlap but divergent age trajectories, highlighting that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.
•Accelerated decrease across hippocampal volumes after 60 years old•Morphometric techniques provide spatially localized information•Posterior hippocampal surface area decreased across ...lifespan•Displacement results indicated an accentuation of the hippocampal curvature with age•Sex, education and cognition involved in the age-related hippocampal shape changes
The study of the hippocampus across the healthy adult lifespan has rendered inconsistent findings. While volumetric measurements have often been a popular technique for analysis, more advanced morphometric techniques have demonstrated compelling results that highlight the importance and improved specificity of shape-based measures. Here, the MAGeT Brain algorithm was applied on 134 healthy individuals aged 18–81 years old to extract hippocampal subfield volumes and hippocampal shape measurements, namely: local surface area (SA) and displacement. We used linear-, second- or third-order natural splines to examine the relationships between hippocampal measures and age. In addition, partial least squares analyses were performed to relate volume and shape measurements with cognitive and demographic information. Volumetric results indicated a relative preservation of the right cornus ammonis 1 with age and a global volume reduction linked with older age, female sex, lower levels of education and cognitive performance. Vertex-wise analysis demonstrated an SA preservation in the anterior hippocampus with a peak during the sixth decade, while the posterior hippocampal SA gradually decreased across lifespan. Overall, SA decrease was linked to older age, female sex and, to a lesser extent lower levels of education and cognitive performance. Outward displacement in the lateral hippocampus and inward displacement in the medial hippocampus were enlarged with older age, lower levels of cognition and education, indicating an accentuation of the hippocampal “C” shape with age. Taken together, our findings suggest that vertex-wise analyses have higher spatial specifity and that sex, education, and cognition are implicated in the differential impact of age on hippocampal subregions throughout its anteroposterior and medial-lateral axes. This article is part of the Virtual Special Issue titled COGNITIVE NEU- ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.
Although brain cholinergic denervation has been largely associated with cognitive decline in patients with Parkinson's disease (PD), new evidence suggests that cholinergic upregulation occurs in the ...hippocampus of PD patients without cognitive deficits. The specific hippocampal sectors and potential mechanisms of this cholinergic compensatory process have been further studied here, using MRI volumetry and morphometry coupled with molecular imaging using the PET radiotracer
F-Fluoroethoxybenzovesamicol (
F-FEOBV). Following a thorough screening procedure, 18 participants were selected and evenly distributed in three groups, including cognitively normal PD patients (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and healthy volunteers (HV). Participants underwent a detailed neuropsychological assessment, structural MRI, and PET imaging with
F-FEOBV. Basal forebrain Ch1-Ch2 volumes were measured using stereotaxic mapping. Hippocampal subfields were automatically defined using the MAGeT-Brain segmentation algorithm. Cholinergic innervation density was quantified using
F-FEOBV uptake. Compared with HV, both PD-CN and PD-MCI displayed significantly reduced volumes in CA2-CA3 bilaterally. We found no other hippocampal subfield nor Ch1-Ch2 volume differences between the three groups. PET imaging revealed higher
F-FEOBV uptake in CA2-CA3 of the PD-CN compared with HV or PD-MCI. A positive correlation was observed between cognitive performances and
F-FEOBV uptake in the right CA2-CA3 subfield. Reduced volume, together with increased
F-FEOBV uptake, were observed specifically in the CA2-CA3 hippocampal subfields. However, while the volume change was observed in both PD-CN and PD-MCI, increased
F-FEOBV uptake was present only in the PD-CN group. This suggests that a cholinergic compensatory process takes place in the atrophied CA2-CA3 hippocampal subfields and might underlie normal cognition in PD.
Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI ...scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices (“Prisma Upgrade protocol”) and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence (“vNav protocol”). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.
Although deep networks have been shown to perform very well on a variety of medical imaging tasks, inference in the presence of pathology presents several challenges to common models. These ...challenges impede the integration of deep learning models into real clinical workflows, where the customary process of cascading deterministic outputs from a sequence of image-based inference steps (e.g. registration, segmentation) generally leads to an accumulation of errors that impacts the accuracy of downstream inference tasks. In this paper, we propose that by embedding uncertainty estimates across cascaded inference tasks, performance on the downstream inference tasks should be improved. We demonstrate the effectiveness of the proposed approach in three different clinical contexts: (i) We demonstrate that by propagating T2 weighted lesion segmentation results and their associated uncertainties, subsequent T2 lesion detection performance is improved when evaluated on a proprietary large-scale, multi-site, clinical trial dataset acquired from patients with Multiple Sclerosis. (ii) We show an improvement in brain tumour segmentation performance when the uncertainty map associated with a synthesised missing MR volume is provided as an additional input to a follow-up brain tumour segmentation network, when evaluated on the publicly available BraTS-2018 dataset. (iii) We show that by propagating uncertainties from a voxel-level hippocampus segmentation task, the subsequent regression of the Alzheimer's disease clinical score is improved.
Abstract
Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we ...investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia.
We collected MRIs from 97 (41 males) right-handed participants aged over 60. We segmented the right and left hippocampi into (i) dentate gyrus and cornu ammonis 4 (DG/CA4); (ii) CA2 and CA3 (CA2/CA3); (iii) CA1; (iv) strata radiatum, lacunosum and moleculare; and (v) subiculum. Memory was assessed with verbal free recall and recognition tasks, as well as visual free recall and recognition tasks. Amyloid-β and hippocampal tau positivity were assessed using 18FAZD4694 and 18FMK6240 PET tracers, respectively.
The verbal free recall and verbal recognition performances were positively associated with CA1 and strata radiatum, lacunosum and moleculare volumes. The verbal free recall and visual free recall were positively correlated with the right DG/CA4. The visual free recall, but not verbal free recall, was also associated with the right CA2/CA3. The visual recognition was not significantly associated with any subfield volume. Hippocampal tau positivity, but not amyloid-β positivity, was associated with reduced DG/CA4, CA2/CA3 and strata radiatum, lacunosum and moleculare volumes.
Our results suggest that memory performances are linked to specific subfields. CA1 appears to contribute to the verbal modality, irrespective of the free recall or recognition mode of retrieval. In contrast, DG/CA4 seems to be involved in the free recall mode, irrespective of verbal or visual modalities. These results are concordant with the view that DG/CA4 plays a primary role in encoding a stimulus’ distinctive attributes, and that CA2/CA3 could be instrumental in recollecting a visual memory from one of its fragments. Overall, we show that hippocampal subfield segmentation can be useful for detecting early volume changes and improve our understanding of the hippocampal subfields’ roles in memory.
In this study, Aumont et al. investigated the hippocampus, a brain region tied to memory. They found that visual memory was associated with the right hippocampus, while verbal memory was associated with both sides in older adults. Additionally, the hippocampus was smaller in the presence of local Alzheimer’s disease signature.
Graphical Abstract
Graphical Abstract
Background
Age‐related memory decline is well associated with hippocampal atrophy, although the specific role of hippocampal subfields in memory function has not been thoroughly investigated yet. In ...this study, we investigated the associations between hippocampal subfield volumes and free recall and recognition performances in verbal and visual memory tasks in older adults without dementia.
Method
We selected 97 right‐handed participants without dementia aged 60 to 85, 42 males, from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. From T2‐weighted MRIs with 0.7*0.7*1mm voxel size, the hippocampi were segmented five subfields: 1) DG (DG); 2) CA2 with CA3 (CA2/CA3); 3) CA1; 4) strata radiatum, lacunosum and moleculare (SRLM); and 5) subiculum by using the MAGeT‐Brain algorithm. Memory was assessed with Rey Auditory Learning test for verbal free recall (RAVLT7) and recognition (RAVLT‐R), and with Aggie Figure Learning test for visual free recall (AFLT7) and recognition (AFLT‐R). Linear models were used to test the association between hippocampal subfield volumes and memory performances with age, sex and total intracranial volume as covariates (p<0.05, corrected for false discovery rate)
Result
The volumes of bilateral CA1 and SRLM were significantly associated with RAVLT7 and RAVLT‐R. The right DG volume was significantly associated with AFLT7 and RAVLT7. AFLT7 was also associated with the volume of right CA2/CA3 while AFLT‐R was not associated with any hippocampal subfield (see Figures 1 & 2).
Conclusion
Our results are consistent with the view that hippocampal subfields contribute differently to memory traces: CA1 for recollection that requires contextual information; the DG for pattern separation (creating new distinct representations of each stimulus); and CA3 for pattern completion (the recollection of a stimulus from a partial memory). Contextual information is more important when recollecting known words, while distinct and efficient encoding may be especially useful for search strategies inherent to free recall. Pattern completion could be particularly useful to efficiently recollect visual figures based on visual features during free recall. Overall, this shows that hippocampal subfield segmentation offers a better understanding of their distinctive roles in cognition.
Background
Age‐related memory decline is well associated with hippocampal atrophy, although the specific role of hippocampal subfields in memory function has not been thoroughly investigated yet. In ...this study, we investigated the associations between hippocampal subfield volumes and free recall and recognition performances in verbal and visual memory tasks in older adults without dementia.
Method
We selected 97 right‐handed participants without dementia aged 60 to 85, 42 males, from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. From T2‐weighted MRIs with 0.7*0.7*1mm voxel size, the hippocampi were segmented five subfields: 1) DG (DG); 2) CA2 with CA3 (CA2/CA3); 3) CA1; 4) strata radiatum, lacunosum and moleculare (SRLM); and 5) subiculum by using the MAGeT‐Brain algorithm. Memory was assessed with Rey Auditory Learning test for verbal free recall (RAVLT7) and recognition (RAVLT‐R), and with Aggie Figure Learning test for visual free recall (AFLT7) and recognition (AFLT‐R). Linear models were used to test the association between hippocampal subfield volumes and memory performances with age, sex and total intracranial volume as covariates (p<0.05, corrected for false discovery rate).
Result
The volumes of bilateral CA1 and SRLM were significantly associated with RAVLT7 and RAVLT‐R. The right DG volume was significantly associated with AFLT7 and RAVLT7. AFLT7 was also associated with the volume of right CA2/CA3 while AFLT‐R was not associated with any hippocampal subfield (see Figures 1 & 2).
Conclusion
Our results are consistent with the view that hippocampal subfields contribute differently to memory traces: CA1 for recollection that requires contextual information; the DG for pattern separation (creating new distinct representations of each stimulus); and CA3 for pattern completion (the recollection of a stimulus from a partial memory). Contextual information is more important when recollecting known words, while distinct and efficient encoding may be especially useful for search strategies inherent to free recall. Pattern completion could be particularly useful to efficiently recollect visual figures based on visual features during free recall. Overall, this shows that hippocampal subfield segmentation offers a better understanding of their distinctive roles in cognition.
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