Patterns of hippocampal atrophy differ among Alzheimer's disease, amnestic mild cognitive impairment, and late‐life depression

Joko, Taisuke; Washizuka, Shinsuke; Sasayama, Daimei; Inuzuka, Shin; Ogihara, Tomomi; Yasaki, Takehiko; Hagiwara, Tetsuya; Sugiyama, Nobuhiro; Takahashi, Tohru; Kaneko, Tomoki; Hanihara, Tokiji; Amano, Naoji

doi:10.1111/psyg.12176

Cited by 24 publications

(20 citation statements)

References 35 publications

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“…28 Consistently, another study found different patterns of hippocampal atrophy among participants with AD, amnestic MCI, and late-life depression. 29 In a prior study, miR-135 was found to be lower in the brain of 11 depressed suicide human subjects by Issler and colleagues. 30 miR-135, however, was not associated with depressive symptoms in the ROS/MAP cohorts (p = 0.06).…”

Section: Discussionmentioning

confidence: 94%

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

et al. 2020

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Late-life depression is associated with an increased risk for dementia but we have limited knowledge of the molecular mechanisms underlying this association. Here we investigated whether brain microRNAs, important posttranscriptional regulators of gene expression, contribute to this association. Late-life depressive symptoms were assessed annually in 300 participants of the Religious Orders Study and Rush Memory and Aging Project for a mean of 7 years. Participants underwent annual cognitive testing, clinical assessment of cognitive status, and uniform neuropathologic examination after death. microRNAs were profiled from the prefrontal cortex using NanoString platform in the discovery cohort and small RNA sequencing in the replication cohort. A global microRNA association study of late-life depressive symptoms was performed using linear mixed model adjusting for the potential confounding factors. Four brain microRNAs were associated with late-life depressive symptoms at adjusted p < 0.05: miR-484, miR-26b-5p, miR-30d-5p, and miR-197-3p. Lower expression levels of these miRNAs were associated having greater depressive symptoms. Furthermore, lower levels of miR-484 and miR-197-3p were associated with faster decline of cognition over time. Moreover, lower miR-484 level was associated with higher probability of having Alzheimer's dementia. Importantly, the associations between miR-484 and depressive symptoms and Alzheimer's dementia, respectively, were replicated in an independent cohort. Lastly, the predicted targets of miR-484 were enriched in a brain protein co-expression module involving synaptic transmission and regulation of synaptic plasticity. This study identified four brain microRNAs associated with late-life depressive symptoms assessed longitudinally. In addition, we found a molecular connection between late-life depression and dementia through miR-484.

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Section: Discussionmentioning

confidence: 94%

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

et al. 2020

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“…β-Amyloid abnormalities and tau pathology in the preclinical stages of AD initially appear in the hippocampus (Braak and Braak, 1991; Hanseeuw et al, 2016; Serra et al, 2018). Longitudinal studies have shown significant volume loss in the hippocampus during the progression of AD, and there is a direct relationship with cognitive decline (Everitt and Dunn, 2013; Joko et al, 2016). Altered functional connectivity (FC) of the hippocampus in patients with MCI and AD has attracted increasing attention from researchers.…”

Section: Introductionmentioning

confidence: 99%

Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer’s Disease: A Resting-State fMRI Study

Xue

Guo

Gao

et al. 2019

Front. Aging Neurosci.

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The hippocampus is generally reported as one of the regions most impacted by Alzheimer’s disease (AD) and is closely associated with memory function and orientation. Undirected functional connectivity (FC) alterations occur in patients with mild cognitive impairment (MCI) and AD, and these alterations have been the subject of many studies. However, abnormal patterns of directed FC remain poorly understood. In this study, to identify changes in directed FC between the hippocampus and other brain regions, Granger causality analysis (GCA) based on voxels was applied to resting-state functional magnetic resonance imaging (rs-fMRI) data from 29 AD, 65 MCI, and 30 normal control (NC) subjects. The results showed significant differences in the patterns of directed FC among the three groups. There were fewer brain regions showing changes in directed FC with the hippocampus in the MCI group than the NC group, and these regions were mainly located in the temporal lobe, frontal lobe, and cingulate cortex. However, regarding the abnormalities in directed FC in the AD group, the number of affected voxels was greater, the size of the clusters was larger, and the distribution was wider. Most of the abnormal connections were unidirectional and showed hemispheric asymmetry. In addition, we also investigated the correlations between the abnormal directional FCs and cognitive and clinical measurement scores in the three groups and found that some of them were significantly correlated. This study revealed abnormalities in the transmission and reception of information in the hippocampus of MCI and AD patients and offer insight into the neurophysiological mechanisms underlying MCI and AD.

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“…Commonly, the patients with MCI and depression have the common cognitive dysfunction profiles [5, 6] and the similar functional alteration pattern, particularly in the medial temporal lobe [7]. These findings indicated the similar neuropathological pathway between MCI and depression [4, 6, 7]. Nevertheless, the patients with MDD and aMCI have been reported with greater neurocognitive dysfunctions, grey matter volume loss, as well as disrupted functional integration and segregation compared to the non-depressed MCI [8–11].…”

Section: Introductionmentioning

confidence: 99%

“…Amnestic mild cognitive impairment (aMCI) is defined as the pre-dementia stage with a prominent memory impairment [ 1 , 2 ]. It has shown that the major depression disorder (MDD) and aMCI have high risk for progression to Alzheimer’s disease (AD), however, the neurobiological mechanisms of this link remain unclear [ 3 , 4 ]. Commonly, the patients with MCI and depression have the common cognitive dysfunction profiles [ 5 , 6 ] and the similar functional alteration pattern, particularly in the medial temporal lobe [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Altered amygdala and hippocampus effective connectivity in mild cognitive impairment patients with depression: a resting-state functional MR imaging study with granger causality analysis

et al. 2017

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Neuroimaging studies have demonstrated that the major depression disorder would increase the risk of dementia in the older with amnestic cognitive impairment. We used granger causality analysis algorithm to explore the amygdala- and hippocampus-based directional connectivity patterns in 12 patients with major depression disorder and amnestic cognitive impairment (mean age: 69.5 ± 10.3 years), 13 amnestic cognitive impairment patients (mean age: 72.7 ± 8.5 years) and 14 healthy controls (mean age: 64.7 ± 7.0 years). Compared with amnestic cognitive impairment patients and control groups respectively, the patients with both major depression disorder and amnestic cognitive impairment displayed increased effective connectivity from the right amygdala to the right lingual and calcarine gyrus, as well as to the bilateral supplementary motor areas. Meanwhile, the patients with both major depression disorder and amnestic cognitive impairment had enhanced effective connectivity from the left superior parietal gyrus, superior and middle occipital gyrus to the left hippocampus, the z values of which was also correlated with the scores of mini-mental state examination and auditory verbal learning test-immediate recall. Our findings indicated that the directional effective connectivity of right amygdala - occipital-parietal lobe – left hippocampus might be the pathway by which major depression disorder inhibited the brain activity in patients with amnestic cognitive impairment.

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Patterns of hippocampal atrophy differ among Alzheimer's disease, amnestic mild cognitive impairment, and late‐life depression

Cited by 24 publications

References 35 publications

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer’s Disease: A Resting-State fMRI Study

Altered amygdala and hippocampus effective connectivity in mild cognitive impairment patients with depression: a resting-state functional MR imaging study with granger causality analysis

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