One-year Follow-up Study of Hippocampal Subfield Atrophy in Alzheimer's Disease and Normal Aging

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: Our findings show that hippocampal subfield atrophy varies among the three study groups.

Low Subicular Volume as an Indicator of Dementia-Risk Susceptibility in Old Age

“…Moreover, subicular volume was found to be the single most predictive hippocampal subfield measure for AD diagnosis (Izzo et al, 2020). The findings of hippocampal subfield atrophy in AD could widely be replicated in patients with MCI, who generally had a more focal pattern of atrophy than AD patients (Chetelat et al, 2008;Mueller and Weiner, 2009;La Joie et al, 2013;de Flores et al, 2015b;Tang et al, 2015;Madusanka et al, 2019;Zhang et al, 2020). Between persons with MCI who converted to AD and non-converters most significant volume differences were reported for the subiculum and presubiculum in the Alzheimer's Disease Neuroimaging Initiative cohort (Vasta et al, 2016).…”

“…Numerous in vivo MRI hippocampal subfield studies reported a significant volume loss of either almost all subfields with most pronounced effects or focal volume loss of CA1 or CA1 and subiculum in clinical manifest AD ( Wang et al, 2006 ; Frisoni et al, 2008 ; Mueller and Weiner, 2009 ; Mueller et al, 2010 ; Apostolova et al, 2012 ; Lindberg et al, 2012 ; Wisse et al, 2014b ; de Flores et al, 2015b ; Perrotin et al, 2015 ; Tang et al, 2015 ; Madusanka et al, 2019 ). Moreover, subicular volume was found to be the single most predictive hippocampal subfield measure for AD diagnosis ( Izzo et al, 2020 ).…”

“…Episodic memory dysfunction in old-aged persons is closely linked to hippocampal volume loss ( Jack et al, 2000 ; Barnes et al, 2009 ; Dickerson and Eichenbaum, 2010 ; Gorbach et al, 2017 ; Nyberg, 2017 ). Considering a high degree of assumed functional specialization, atrophy of distinct hippocampal subfields may even better reflect earliest pathological changes of AD trajectories ( de Flores et al, 2015a ; Perrotin et al, 2015 ; Lindberg et al, 2017 ; Evans et al, 2018 ; Liang et al, 2018 ; Madusanka et al, 2019 ; Parker et al, 2019 ; Zhao et al, 2019 ; Dounavi et al, 2020 ; McKeever et al, 2020 ; Wong et al, 2020 ; Zhang et al, 2020 ).…”

SRXN1 blood levels negatively correlate with hippocampal atrophy and cognitive decline

“…A recent study conducted on subjects selected from Alzheimer’s Disease Neuroimaging Initiative (ADNI), investigating hippocampal subfield volumes, identified that atrophy of the bilateral CA1, CA2-CA4 and subiculum subfields was higher in AD patients compared to mild cognitive impairment (MCI) individuals and controls, and registered a high atrophy rate in whole hippocampus, CA1 and subiculum subfields of MCI. 4 Despite its high diagnostic potential, MRI displays discomforts and feasibility issues, occurring mostly in elderly individuals. 5 , 6…”

Involvement of the Hypothalamic Nuclei in Forming Object–Place Associations in Neurons of Hippocampal Field CA2 (a hypothetical mechanism)

“…In Alzheimer's disease, the hippocampus also shows cell atrophy, especially in fi elds CA2 and CA1, as well as in the basolateral nucleus of the amygdala, which is connected with it [Tang et al, 2016]. In Alzheimer's disease, atrophy in fi elds CA1, CA2, and CA4 was greater than in a control group of elderly people [Madusanka et al, 2019]. As the target cells of fi eld CA2 PN are neurons in fi eld CA1, it was suggested that impairments to contextual memory in Parkinson's cesses, they may be useful for the targeted search for drugs ameliorating the symptoms of various neurodegenerative diseases associated with anomalous functioning of this structure.…”