Polygenic hazard score modified the relationship between hippocampal subfield atrophy and episodic memory in older adults

Xu, Jingjing; Guan, Xiaojun; Wen, Jiaqi; Zhang, Minming; Xu, Xiaojun

doi:10.3389/fnagi.2022.943702

Cited by 3 publications

(2 citation statements)

References 74 publications

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“…Damage to the hippocampal fimbria can disrupt the cholinergic system and cause spatial orientation difficulties and memory deficits in animals ( Cassel et al, 1997 ). Smaller hippocampal fimbria volume was associated with poorer cognitive function in patients with Alzheimer’s disease ( Evans et al, 2018 ; Xu et al, 2022 ). This may be related to its anatomical connections and functional pathways.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

et al. 2023

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ObjectiveThe aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ).MethodsPatients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons.ResultsSixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)].ConclusionOxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

et al. 2023

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“…The fimbria, part of the hippocampus, plays a crucial role in the input and output pathways of the hippocampus. A previous study has suggested that a smaller fimbria is associated with poorer cognitive function in patients with AD (61). This association may be related to the fimbria's anatomical connections and functional pathways.…”

Section: Subcortical Morphological Alterationmentioning

confidence: 91%

Altered cortical and subcortical morphometric features and asymmetries in the subjective cognitive decline and mild cognitive impairment

Yang,

Liang,

Wei

et al. 2023

Front. Neurol.

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IntroductionThis study aimed to evaluate morphological changes in cortical and subcortical regions and their asymmetrical differences in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). These morphological changes may provide valuable insights into the early diagnosis and treatment of Alzheimer's disease (AD).MethodsWe conducted structural MRI scans on a cohort comprising 62 SCD patients, 97 MCI patients, and 70 age-, sex-, and years of education-matched healthy controls (HC). Using Freesurfer, we quantified surface area, thickness, the local gyrification index (LGI) of cortical regions, and the volume of subcortical nuclei. Asymmetry measures were also calculated. Additionally, we explored the correlation between morphological changes and clinical variables related to cognitive decline.ResultsCompared to HC, patients with MCI exhibited predominantly left-sided surface morphological changes in various brain regions, including the transverse temporal gyrus, superior temporal gyrus, insula, and pars opercularis. SCD patients showed relatively minor surface morphological changes, primarily in the insula and pars triangularis. Furthermore, MCI patients demonstrated reduced volumes in the anterior-superior region of the right hypothalamus, the fimbria of the bilateral hippocampus, and the anterior region of the left thalamus. These observed morphological changes were significantly associated with clinical ratings of cognitive decline.ConclusionThe findings of this study suggest that cortical and subcortical morphometric changes may contribute to cognitive impairment in MCI, while compensatory mechanisms may be at play in SCD to preserve cognitive function. These insights have the potential to aid in the early diagnosis and treatment of AD.

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Progression of hippocampal subfield atrophy and asymmetry in Alzheimer's disease

Xu,

Tan,

Wen

et al. 2024

Eur J of Neuroscience

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Alzheimer's disease (AD) affects the hippocampus during its progression, but the specific observable changes of hippocampal subfields during disease progression remain poorly understood. In this study, we employed an event‐based model (EBM) to determine the sequence of occurrence of hippocampal subfield atrophy in mild cognitive impairment (MCI) and AD cohorts. Subjects (207) were included: 86 MCI, 53 AD, and 68 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent structural magnetic resonance imaging (MRI) scans to analyse the hippocampal subfields. We assigned each patient to a specific EBM stage, based on the number of their abnormal subfields. A combination of 2‐year follow‐up MRI scans were applied to demonstrate the longitudinal consistency and utility of the model's staging system. The model estimated that the earliest atrophy occurs in the hippocampal fissure, then spreading to other subregions in both MCI and AD. We identified a marked divergence between the sequences of left and right hippocampal subfields atrophy, so inter‐hemispheric asymmetry pattern was further analysed. The sequence of asymmetry index (AI) increases beginning in the molecular and granule cell layers of the dentate gyrus (GC‐ML‐DG), cornus ammonis (CA) 4, and the molecular layer (ML). Longitudinal analysis confirms the efficacy of the model. In addition, the model stages were significantly correlated with patients' memory scores (p < .05). Collectively, we used a data‐driven method to provide new insight into AD hippocampal progression. The present model could aid in understanding of the disease stages, as well as tracking memory decline.

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Polygenic hazard score modified the relationship between hippocampal subfield atrophy and episodic memory in older adults

Cited by 3 publications

References 74 publications

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

Altered cortical and subcortical morphometric features and asymmetries in the subjective cognitive decline and mild cognitive impairment

Progression of hippocampal subfield atrophy and asymmetry in Alzheimer's disease

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