CA4
Carbonic anhydrase 4 precursor (EC 4.2.1.1) (Carbonate dehydratase IV) (Carbonic anhydrase IV) (CA-IV)
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Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: -0.68%/year; subiculum: -0.99%/year; and CA4-DG: -1.39%/year; p < 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Atrophy
- Cohort Studies
- Cross-Sectional Studies
- Dentate Gyrus
- Female
- Hippocampus
- Humans
- Magnetic Resonance Imaging
- Male
- Neuropsychological Tests
- Risk
Keywords
- Aging
- Alzheimer's disease
- Hippocampal subfields
- MRI
In this study, we investigated the effect of hippocampal subfield atrophy on the development of Alzheimer's disease (AD) by analyzing baseline magnetic resonance images (MRI) and images collected over a one-year follow-up period. Previous studies have suggested that morphological changes to the hippocampus are involved in both normal ageing and the development of AD. The volume of the hippocampus is an authentic imaging biomarker for AD. However, the diverse relationship of anatomical and complex functional connectivity between different subfields implies that neurodegenerative disease could lead to differences between the atrophy rates of subfields. Therefore, morphometric measurements at subfield-level could provide stronger biomarkers. Hippocampal subfield atrophies are measured using MRI scans, taken at multiple time points, and shape-based normalization to a Montreal neurological institute (MNI) ICBM 152 nonlinear atlas. Ninety subjects were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI), and divided equally into Healthy Controls (HC), AD, and mild cognitive impairment (MCI) groups. These subjects underwent serial MRI studies at three time-points: baseline, 6 months and 12 months. We analyzed the subfield-level hippocampal morphometric effects of normal ageing and AD based on radial distance mapping and volume measurements. We identified a general trend and observed the largest hippocampal subfield atrophies in the AD group. Atrophy of the bilateral CA1, CA2- CA4 and subiculum subfields was higher in the case of AD than in MCI and HC. We observed the highest rate of reduction in the total volume of the hippocampus, especially in the CA1 and subiculum regions, in the case of MCI. Our findings show that hippocampal subfield atrophy varies among the three study groups.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Atrophy
- Case-Control Studies
- Cognitive Dysfunction
- Disease Progression
- Female
- Follow-Up Studies
- Hippocampus
- Humans
- Magnetic Resonance Imaging
- Male
- Neuroimaging
Keywords
- Alzheimer's disease
- biomarker
- hippocampal
- mild cognitive impairment
- neurodegenerative diseases
- normal aging
- radial distance
- subfield atrophy
The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the [i]Healthy Brain Aging (HBA) Clinic[/i] and diagnosed with aMCI ([i]n[/i] = 38), naMCI ([i]n[/i] = 84) or subjective memory complaints (SMC; [i]n[/i] = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.
Keywords
- aging
- hippocampus
- memory
- mild cognitive impairment
- neuroimaging
- subfields
The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50 . We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Female
- Hippocampus
- Humans
- Image Interpretation, Computer-Assisted
- Ireland
- Longitudinal Studies
- Magnetic Resonance Imaging
- Male
- Memory
- Middle Aged
- Neuropsychological Tests
- Organ Size
- Pattern Recognition, Automated
- Semantics
{{medline-entry |title=Aerobic exercise increases hippocampal subfield volumes in younger adults and prevents volume decline in the elderly. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30927200 |abstract=Exercise improves both physical and mental health and increases neurogenesis in the dendate gyrus (DG) of the hippocampus. The aim of this study was to examine whether exercising, as compared to no change in regular physical activity, would impact on hippocampal volume, and in particular the core hippocampal structures, DG and cornu ammonis (CA) subfields, and whether any changes would be moderated by age. Thirty nine previously sedentary healthy participants were randomized to either a standardized progressive aerobic exercise program or to "no change" for 16 weeks. Mental health including profile of mood states (POMS), was assessed before and every 4 weeks during the program. Magnetic resonance imaging to examine hippocampal subfields was carried out before and after the program. Aerobic exercise resulted in a significant improvement of the POMS item 'vigour' compared to those in the control group. Overall left hippocampal and left CA4-DG volumes increased significantly in the exercise group while no significant changes were seen in the control group. Older adults in the control group demonstrated significant reductions in CA4-DG subfields over the study, whereas older adults in the exercise group did not show volume decline. These findings reinforce the literature that exercise has a beneficial effect on mental health and can prevent age-related volume decline. Exercise to Improve Resilience, https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1