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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Cross-Sectional Study

The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer’s Disease Patients with Depression

Author(s): Haokai Zhu, Hong Zhu, Xiaozheng Liu, Fuquan Wei, Huichao Li and Zhongwei Guo*

Volume 19, Issue 14, 2022

Published on: 07 March, 2023

Page: [965 - 975] Pages: 11

DOI: 10.2174/1567205020666230303093112

Price: $65


Background: Depression is one of the most common neuropsychiatric symptoms of Alzheimer’s disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients.

Objective: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (DAD).

Methods: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups.

Results: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus.

Conclusion: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.

Keywords: Alzheimer’s disease, depression, resting state functional MRI, functional connectivity, entorhinal cortex, postcentral gyrus.

Alzheimer’s Association. 2022 Alzheimer’s disease facts and figures. Alzheimers Dement 2022; 18(4): 700-89.
[] [PMID: 35289055]
Zhao QF, Tan L, Wang HF, et al. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: Systematic review and meta-analysis. J Affect Disord 2016; 190: 264-71.
[] [PMID: 26540080]
Hurt C, Bhattacharyya S, Burns A, et al. Patient and caregiver perspectives of quality of life in dementia. An investigation of the relationship to behavioural and psychological symptoms in dementia. Dement Geriatr Cogn Disord 2008; 26(2): 138-46.
[] [PMID: 18679028]
Kim B, Noh GO, Kim K. Behavioural and psychological symptoms of dementia in patients with Alzheimer’s disease and family caregiver burden: a path analysis. BMC Geriatr 2021; 21(1): 160.
[] [PMID: 33663416]
He Y, Li H, Huang J, et al. Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: A systematic review and network meta-analysis. J Psychopharmacol 2021; 35(8): 901-9.
[] [PMID: 34238048]
Perini G, Cotta Ramusino M, Sinforiani E, Bernini S, Petrachi R, Costa A. Cognitive impairment in depression: Recent advances and novel treatments. Neuropsychiatr Dis Treat 2019; 15: 1249-58.
[] [PMID: 31190831]
Gerlei KZ, Brown CM, Sürmeli G, Nolan MF. Deep entorhinal cortex: From circuit organization to spatial cognition and memory. Trends Neurosci 2021; 44(11): 876-87.
[] [PMID: 34593254]
Sugar J, Moser MB. Episodic memory: Neuronal codes for what, where, and when. Hippocampus 2019; 29(12): 1190-205.
[] [PMID: 31334573]
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurol 2007; 6(8): 734-46.
[] [PMID: 17616482]
Olsen RK, Yeung LK, Noly-Gandon A, et al. Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis. Neurobiol Aging 2017; 57: 195-205.
[] [PMID: 28578804]
Gerritsen L, Comijs HC, van der Graaf Y, Knoops AJG, Penninx BWJH, Geerlings MI. Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes - the SMART Medea study. Biol Psychiatry 2011; 70(4): 373-80.
[] [PMID: 21439552]
O’Shea DM, Dotson VM, Woods AJ, et al. Depressive symptom dimensions and their association with hippocampal and entorhinal cortex volumes in community dwelling older adults. Front Aging Neurosci 2018; 10: 40.
[] [PMID: 29515435]
Chen X, Lan T, Wang Y, et al. Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression. Aging 2020; 12(3): 3042-52.
[] [PMID: 32074509]
Lu J, Zhang Z, Yin X, et al. An entorhinal-visual cortical circuit regulates depression-like behaviors. Mol Psychiatry 2022; 27(9): 3807-20.
[] [PMID: 35388184]
Jalilianhasanpour R, Beheshtian E, Sherbaf G, Sahraian S, Sair HI. Functional connectivity in neurodegenerative disorders. Top Magn Reson Imaging 2019; 28(6): 317-24.
[] [PMID: 31794504]
Li J, Chen J, Kong W, Li X, Hu B. Abnormal core functional connectivity on the pathology of MDD and antidepressant treatment: A systematic review. J Affect Disord 2022; 296: 622-34.
[] [PMID: 34688026]
Karbasforoushan H, Woodward ND. Resting-state networks in schizophrenia. Curr Top Med Chem 2012; 12(21): 2404-14.
[] [PMID: 23279179]
Carmichael O, Schwarz AJ, Chatham CH, et al. The role of fMRI in drug development. Drug Discov Today 2018; 23(2): 333-48.
[] [PMID: 29154758]
Agosta F, Pievani M, Geroldi C, Copetti M, Frisoni GB, Filippi M. Resting state fMRI in Alzheimer’s disease: Beyond the default mode network. Neurobiol Aging 2012; 33(8): 1564-78.
[] [PMID: 21813210]
Tozzi L, Zhang X, Chesnut M, Holt-Gosselin B, Ramirez CA, Williams LM. Reduced functional connectivity of default mode network subsystems in depression: Meta-analytic evidence and relationship with trait rumination. Neuroimage Clin 2021; 30: 102570.
[] [PMID: 33540370]
Guo Z, Liu X, Xu S, et al. Abnormal changes in functional connectivity between the amygdala and frontal regions are associated with depression in Alzheimer’s disease. Neuroradiology 2018; 60(12): 1315-22.
[] [PMID: 30242429]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[] [PMID: 21514250]
Gmitrowicz A, Kucharska A. Developmental disorders in the fourth edition of the American classification: diagnostic and statistical manual of mental disorders (DSM IV optional book). Psychiatria Polska 1994; 28(5): 509-21.
Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6(4): 278-96.
[] [PMID: 6080235]
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994; 44(12): 2308-14.
[] [PMID: 7991117]
Schneider LS, Tariot PN, Lyketsos CG, et al. National institute of mental health clinical antipsychotic trials of intervention effectiveness (CATIE): Alzheimer disease trial methodology. Am J Geriatr Psychiatry 2001; 9(4): 346-60.
[] [PMID: 11739062]
Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 2003; 19(3): 1233-9.
[] [PMID: 12880848]
Ledberg A, Åkerman S, Roland PE. Estimation of the probabilities of 3D clusters in functional brain images. Neuroimage 1998; 8(2): 113-28.
[] [PMID: 9740755]
Phan KL, Wager T, Taylor SF, Liberzon I. Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 2002; 16(2): 331-48.
[] [PMID: 12030820]
Krause FC, Linardatos E, Fresco DM, Moore MT. Facial emotion recognition in major depressive disorder: A meta-analytic review. J Affect Disord 2021; 293: 320-8.
[] [PMID: 34229285]
Sato W, Kochiyama T, Uono S, et al. Bidirectional electric communication between the inferior occipital gyrus and the amygdala during face processing. Hum Brain Mapp 2017; 38(9): 4511-24.
[] [PMID: 28573679]
Zaninotto L, Solmi M, Veronese N, et al. A meta-analysis of cognitive performance in melancholic versus non-melancholic unipolar depression. J Affect Disord 2016; 201: 15-24.
[] [PMID: 27156095]
Zhang Y, Cui X, Ou Y, et al. Differentiating melancholic and non-melancholic major depressive disorder using fractional amplitude of low-frequency fluctuations. Front Psychiatry 2022; 12: 763770.
[] [PMID: 35185634]
Xie Y, Yang Q, Liu C, Zhang Q, Jiang J, Han Y. Exploring the pattern associated with longitudinal changes of β-amyloid deposition during cognitively normal healthy aging. Front Med 2021; 7: 617173.
[] [PMID: 33585514]
Catricalà E, Polito C, Presotto L, et al. Neural correlates of naming errors across different neurodegenerative diseases. Neurology 2020; 95(20): e2816-30.
[] [PMID: 33004608]
McDonald CR, McEvoy LK, Gharapetian L, et al. Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology 2009; 73(6): 457-65.
[] [PMID: 19667321]
Lim TS, Iaria G, Moon SY. Topographical disorientation in mild cognitive impairment: A voxel-based morphometry study. J Clin Neurol 2010; 6(4): 204-11.
[] [PMID: 21264201]
Yu Y, Li Z, Lin Y, et al. Depression affects intrinsic brain activity in patients with mild cognitive impairment. Front Neurosci 2019; 13: 1333.
[] [PMID: 31920500]
Kropf E, Syan SK, Minuzzi L, Frey BN. From anatomy to function: The role of the somatosensory cortex in emotional regulation. Br J Psychiatry 2019; 41(3): 261-9.
[] [PMID: 30540029]
Kaas JH, Nelson RJ, Sur M, Lin CS, Merzenich MM. Multiple representations of the body within the primary somatosensory cortex of primates. Science 1979; 204(4392): 521-3.
[] [PMID: 107591]
Timmermann L, Ploner M, Haucke K, Schmitz F, Baltissen R, Schnitzler A. Differential coding of pain intensity in the human primary and secondary somatosensory cortex. J Neurophysiol 2001; 86(3): 1499-503.
[] [PMID: 11535693]
Hou Q, Wang C, Hou C, et al. Individual differences in pain sensitivity in drug-naive patients with major depressive disorder: An fMRI study. Brain Imaging Behav 2021; 15(3): 1335-43.
[] [PMID: 32712795]
Liu P, Tu H, Zhang A, et al. Brain functional alterations in MDD patients with somatic symptoms: A resting-state fMRI study. J Affect Disord 2021; 295: 788-96.
[] [PMID: 34517253]
Malejko K, Brown RC, Plener PL, Bonenberger M, Graf H, Abler B. Differential neural processing of unpleasant sensory stimulation in patients with major depression. Eur Arch Psychiatry Clin Neurosci 2021; 271(3): 557-65.
[] [PMID: 32279144]
Gasquoine PG. Localization of function in anterior cingulate cortex: From psychosurgery to functional neuroimaging. Neurosci Biobehav Rev 2013; 37(3): 340-8.
[] [PMID: 23313645]
Chen Z, Peng W, Sun H, et al. High-field magnetic resonance imaging of structural alterations in first-episode, drug-naive patients with major depressive disorder. Transl Psychiatry 2016; 6(11): e942.
[] [PMID: 27824357]
Xu D, Xu G, Zhao Z, Sublette ME, Miller JM, Mann JJ. Diffusion tensor imaging brain structural clustering patterns in major depressive disorder. Hum Brain Mapp 2021; 42(15): 5023-36.
[] [PMID: 34312935]
Lai CH, Wu YT. The patterns of fractional amplitude of low-frequency fluctuations in depression patients: The dissociation between temporal regions and fronto-parietal regions. J Affect Disord 2015; 175: 441-5.
[] [PMID: 25679198]
Mao N, Che K, Chu T, et al. Aberrant resting-state brain function in adolescent depression. Front Psychol 2020; 11: 1784.
[] [PMID: 32903315]
Zhang H, Qiu M, Ding L, et al. Intrinsic gray-matter connectivity of the brain in major depressive disorder. J Affect Disord 2019; 251: 78-85.
[] [PMID: 30909161]
Guo Z, Liu X, Hou H, Wei F, Liu J, Chen X. Abnormal degree centrality in Alzheimer’s disease patients with depression: A resting-state functional magnetic resonance imaging study. Exp Gerontol 2016; 79: 61-6.
[] [PMID: 27079332]
Segura B, Baggio HC, Solana E, et al. Neuroanatomical correlates of olfactory loss in normal aged subjects. Behav Brain Res 2013; 246: 148-53.
[] [PMID: 23458742]
Soudry Y, Lemogne C, Malinvaud D, Consoli SM, Bonfils P. Olfactory system and emotion: Common substrates. Eur Ann Otorhinolaryngol Head Neck Dis 2011; 128(1): 18-23.
[] [PMID: 21227767]
Croy I, Drechsler E, Hamilton P, Hummel T, Olausson H. Olfactory modulation of affective touch processing — A neurophysiological investigation. Neuroimage 2016; 135: 135-41.
[] [PMID: 27138206]
Kim B-Y, Bae JH. Olfactory function and depression: A meta-analysis. Ear Nose Throat J 2022; 1455613211056553.
[PMID: 35360974]
Marin C, Vilas D, Langdon C, et al. Olfactory dysfunction in neurodegenerative diseases. Curr Allergy Asthma Rep 2018; 18(8): 42.
[] [PMID: 29904888]
Devanand DP, Liu X, Tabert MH, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer’s disease. Biol Psychiatry 2008; 64(10): 871-9.
[] [PMID: 18723162]
Benarroch EE. Olfactory system: Functional organization and involvement in neurodegenerative disease. Neurology 2010; 75(12): 1104-9.
[] [PMID: 20855854]
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82(4): 239-59.
[] [PMID: 1759558]
Banaszkiewicz A, Bola Ł, Matuszewski J, et al. The role of the superior parietal lobule in lexical processing of sign language: Insights from fMRI and TMS. Cortex 2021; 135: 240-54.
[] [PMID: 33401098]
Koenigs M, Barbey AK, Postle BR, Grafman J. Superior parietal cortex is critical for the manipulation of information in working memory. J Neurosci 2009; 29(47): 14980-6.
[] [PMID: 19940193]
Frisoni GB, Lorenzi M, Caroli A, Kemppainen N, Någren K, Rinne JO. In vivo mapping of amyloid toxicity in Alzheimer disease. Neurology 2009; 72(17): 1504-11.
[] [PMID: 19398705]
Kaneta T, Katsuse O, Hirano T, et al. Voxel-wise correlations between cognition and cerebral blood flow using arterial spin-labeled perfusion MRI in patients with Alzheimer’s disease: A cross-sectional study. BMC Neurol 2017; 17(1): 91.
[] [PMID: 28506213]
Wu H, Song Y, Chen S, et al. An activation likelihood estimation meta-analysis of specific functional alterations in dorsal attention network in mild cognitive impairment. Front Neurosci 2022; 16: 876568.
[] [PMID: 35557608]
Uddin LQ, Yeo BTT, Spreng RN. Towards a universal taxonomy of macro-scale functional human brain networks. Brain Topogr 2019; 32(6): 926-42.
[] [PMID: 31707621]
Kaiser RH, Andrews-Hanna JR, Wager TD, Pizzagalli DA. Large-scale network dysfunction in major depressive disorder. JAMA Psychiatry 2015; 72(6): 603-11.
[] [PMID: 25785575]
Avnioglu S, Velioglu HA, Cankaya S, Yulug B. Quantitative evaluation of brain volumes in drug-free major depressive disorder using MRI-Cloud method. Neuroreport 2021; 32(12): 1027-34.
[] [PMID: 34075004]
Bennabi D, Vandel P, Papaxanthis C, Pozzo T, Haffen E. Psychomotor retardation in depression: A systematic review of diagnostic, pathophysiologic, and therapeutic implications. BioMed Res Int 2013; 2013: 1-18.
[] [PMID: 24286073]
Wu Z, Gao Y, Potter T, et al. Interactions between aging and Alzheimer’s disease on structural brain networks. Front Aging Neurosci 2021; 13: 639795.
[] [PMID: 34177548]
Veale T, Malone IB, Poole T, et al. Loss and dispersion of superficial white matter in Alzheimer’s disease: A diffusion MRI study. Brain Commun 2021; 3(4): fcab272.
[] [PMID: 34859218]
Pan J, Zhan L, Hu C, et al. Emotion regulation and complex brain networks: Association between expressive suppression and efficiency in the fronto-parietal network and default-mode network. Front Hum Neurosci 2018; 12: 70.
[] [PMID: 29662443]
Zhang B, Lin P, Shi H, et al. Mapping anhedonia-specific dysfunction in a transdiagnostic approach: An ALE meta-analysis. Brain Imaging Behav 2016; 10(3): 920-39.
[] [PMID: 26487590]
Sendi MSE, Zendehrouh E, Fu Z, et al. Disrupted dynamic functional network connectivity among cognitive control networks in the progression of Alzheimer’s Disease. Brain Connect 2021; 2020: 0847.
[] [PMID: 34102870]
Talati A, Hirsch J. Functional specialization within the medial frontal gyrus for perceptual go/no-go decisions based on “what,” “when,” and “where” related information: An fMRI study. J Cogn Neurosci 2005; 17(7): 981-93.
[] [PMID: 16102231]
Liu X, Wang S, Zhang X, Wang Z, Tian X, He Y. Abnormal amplitude of low-frequency fluctuations of intrinsic brain activity in Alzheimer’s disease. J Alzheimers Dis 2014; 40(2): 387-97.
[] [PMID: 24473186]
Woodward MC, Rowe CC, Jones G, Villemagne VL, Varos TA. Differentiating the frontal presentation of Alzheimer’s disease with FDG-PET. J Alzheimers Dis 2015; 44(1): 233-42.
[] [PMID: 25261443]
Cajanus A, Solje E, Koikkalainen J, et al. The association between distinct frontal brain volumes and behavioral symptoms in mild cognitive impairment, Alzheimer’s disease, and frontotemporal dementia. Front Neurol 2019; 10: 1059.
[] [PMID: 31632342]
Li X, Zheng L, Zhang J, et al. Differences in functional brain activation and hippocampal volume among amnestic mild cognitive impairment subtypes. Curr Alzheimer Res 2013; 10(10): 1080-9.
[] [PMID: 24156264]
Toga AW, Thompson PM. Mapping brain asymmetry. Nat Rev Neurosci 2003; 4(1): 37-48.
[] [PMID: 12511860]
Ramirez-Carmona R, Garcia-Lazaro HG, Dominguez-Corrales B, Aguilar-Castañeda E, Roldan-Valadez E. Main effects and interactions of cerebral hemispheres, gender, and age in the calculation of volumes and asymmetries of selected structures of episodic memory. Funct Neurol 2016; 31(4): 257-64.
[PMID: 28072386]
Fu Z, Zhao M, Wang X, et al. Altered neuroanatomical asymmetries of subcortical structures in subjective cognitive decline, amnestic mild cognitive impairment, and Alzheimer’s Disease. J Alzheimers Dis 2021; 79(3): 1121-32.
[] [PMID: 33386805]
Carballedo A, Scheuerecker J, Meisenzahl E, et al. Functional connectivity of emotional processing in depression. J Affect Disord 2011; 134(1-3): 272-9.
[] [PMID: 21757239]
Jiang X, Shen Y, Yao J, et al. Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder. Transl Psychiatry 2019; 9(1): 136.
[] [PMID: 30979866]
Zuo Z, Ran S, Wang Y, et al. Asymmetry in cortical thickness and subcortical volume in treatment-naïve major depressive disorder. Neuroimage Clin 2019; 21: 101614.
[] [PMID: 30528958]
Jesulola E, Sharpley CF, Bitsika V, Agnew LL, Wilson P. Frontal alpha asymmetry as a pathway to behavioural withdrawal in depression: Research findings and issues. Behav Brain Res 2015; 292: 56-67.
[] [PMID: 26051816]
Guo Z, Liu X, Jia X, et al. Regional coherence changes in Alzheimer’s disease patients with depressive symptoms: A resting-state functional MRI study. J Alzheimers Dis 2015; 48(3): 603-11.
[] [PMID: 26445159]
Kim JH, Lee JW, Kim GH, et al. Cortical asymmetries in normal, mild cognitive impairment, and Alzheimer’s disease. Neurobiol Aging 2012; 33(9): 1959-66.
[] [PMID: 21907459]

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