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European Radiology
Published in: European Radiology 9/2017

Open Access 01-09-2017 | Neuro

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Authors: Janne M. Papma, Marion Smits, Marius de Groot, Francesco U. Mattace Raso, Aad van der Lugt, Henri A. Vrooman, Wiro J. Niessen, Peter J. Koudstaal, John C. van Swieten, Frederik M. van der Veen, Niels D. Prins

Published in: European Radiology | Issue 9/2017

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Abstract

Objectives

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI).

Method

MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus.

Results

We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors.

Conclusions

Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI.

Key Points

• PCC functioning during episodic memory relates to hippocampal functioning in MCI.
• PCC functioning during episodic memory does not relate to hippocampal structure in MCI.
• Functional network changes are an important predictor of PCC functioning in MCI.
Appendix
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Literature
1.
Albert MS, DeKosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment 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 7:270–279CrossRefPubMedPubMedCentral
2.
Bruscoli M, Lovestone S (2004) Is MCI really just early dementia? A systematic review of conversion studies. Int Psychogeriatr 16:129–140CrossRefPubMed
3.
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308CrossRefPubMed
4.
5.
Petersen RC, Doody R, Kurz A et al (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992CrossRefPubMed
6.
7.
Papez JW (1937) A proposed mechanism of emotion. Arch Neurol Psychiatr 38:9CrossRef
8.
Aggleton JP, Pralus A, Nelson AJ, Hornberger M (2016) Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit. Brain 139:1877–1890CrossRefPubMedPubMedCentral
9.
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 101:4637–4642CrossRefPubMedPubMedCentral
10.
11.
12.
Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P (2005) Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study. Hum Brain Mapp 26:231–239CrossRefPubMed
13.
Guedj E, Barbeau EJ, Didic M et al (2009) Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation? Eur J Nucl Med Mol Imaging 36:1101–1112CrossRefPubMed
14.
Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC (2003) Mild cognitive impairment Can FDG-PET predict who is to rapidly convert to Alzheimer’s disease? Neurology 60:1374–1377CrossRefPubMed
15.
Ishii K, Mori T, Hirono N, Mori E (2003) Glucose metabolic dysfunction in subjects with a clinical dementia rating of 0.5. J Neurol Sci 215:71–74CrossRefPubMed
16.
Nestor PJ, Fryer TD, Ikeda M, Hodges JR (2003) Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease). Eur J Neurosci 18:2663–2667CrossRefPubMed
17.
Frings L, Dressel K, Abel S et al (2010) Reduced precuneus deactivation during object naming in patients with mild cognitive impairment, Alzheimer’s disease, and frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 30:334–343CrossRefPubMed
18.
Jagust W, Gitcho A, Sun F, Kuczynski B, Mungas D, Haan M (2006) Brain imaging evidence of preclinical Alzheimer's disease in normal aging. Ann Neurol 59:673–681CrossRefPubMed
19.
Johnson SC, Schmitz TW, Moritz CH et al (2006) Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment. Neurobiol Aging 27:1604–1612CrossRefPubMed
20.
Huang C, Wahlund L-O, Svensson L, Winblad B, Julin P (2002) Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurol 2:9CrossRefPubMedPubMedCentral
21.
Petrella JR, Wang L, Krishnan S et al (2007) Cortical deactivation in mild cognitive impairment: high-field-strength functional MR imaging 1. Radiology 245:224–235CrossRefPubMed
22.
Aggleton JP, Brown MW (1999) Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav Brain Sci 22:425–444, discussion 444-489PubMed
23.
Chételat G, Desgranges B, de la Sayette V et al (2003) Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain 126:1955–1967CrossRefPubMed
24.
Kim J, Kim Y-H, Lee J-H (2013) Hippocampus–precuneus functional connectivity as an early sign of Alzheimer's disease: a preliminary study using structural and functional magnetic resonance imaging data. Brain Res 1495:18–29CrossRefPubMed
25.
Jobst KA, Smith AD, Barker CS et al (1992) Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease. J Neurol Neurosurg Psychiatry 55:190–194CrossRefPubMedPubMedCentral
26.
Villain N, Fouquet M, Baron J-C et al (2010) Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease. Brain 133:3301–3314CrossRefPubMedPubMedCentral
27.
Gili T, Cercignani M, Serra L et al (2011) Regional brain atrophy and functional disconnection across Alzheimer's disease evolution. J Neurol Neurosurg Psychiatry 82:58–66CrossRefPubMed
28.
Yakushev I, Schreckenberger M, Müller MJ et al (2011) Functional implications of hippocampal degeneration in early Alzheimer’s disease: a combined DTI and PET study. Eur J Nucl Med Mol Imaging 38:2219–2227CrossRefPubMed
29.
Bai F, Zhang Z, Watson DR, Yu H, Shi Y, Yuan Y (2009) Abnormal white matter independent of hippocampal atrophy in amnestic type mild cognitive impairment. Neurosci Lett 462:147–151CrossRefPubMed
30.
Zhuang L, Sachdev PS, Trollor JN et al (2013) Microstructural white matter changes, not hippocampal atrophy, detect early amnestic mild cognitive impairment. PLoS One 8:e58887CrossRefPubMedPubMedCentral
31.
Huijbers W, Pennartz CM, Cabeza R, Daselaar SM (2011) The hippocampus is coupled with the default network during memory retrieval but not during memory encoding. PLoS One 6:e17463CrossRefPubMedPubMedCentral
32.
Clement F, Belleville S, Mellah S (2010) Functional neuroanatomy of the encoding and retrieval processes of verbal episodic memory in MCI. Cortex 46:1005–1015CrossRefPubMed
33.
Hedden T, Van Dijk KRA, Becker JA et al (2009) Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci 29:12686–12694CrossRefPubMedPubMedCentral
34.
Huang H, Fan X, Weiner M et al (2012) Distinctive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization. Neurobiol Aging 33:2029–2045CrossRefPubMed
35.
Pengas G, Hodges JR, Watson P, Nestor PJ (2010) Focal posterior cingulate atrophy in incipient Alzheimer's disease. Neurobiol Aging 31:25–33CrossRefPubMed
36.
Rémy F, Vayssière N, Saint-Aubert L, Barbeau E, Pariente J (2015) White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance. NeuroImage: Clin 7:482–492CrossRef
37.
Tijms BM, Wink AM, de Haan W et al (2013) Alzheimer's disease: connecting findings from graph theoretical studies of brain networks. Neurobiol Aging 34:2023–2036CrossRefPubMed
38.
Bozzali M, Giulietti G, Basile B et al (2012) Damage to the cingulum contributes to Alzheimer's disease pathophysiology by deafferentation mechanism. Hum Brain Mapp 33:1295–1308CrossRefPubMed
39.
Delano-Wood L, Stricker NH, Sorg SF et al (2012) Posterior cingulum white matter disruption and its associations with verbal memory and stroke risk in mild cognitive impairment. J Alzheimers Dis 29:589PubMedPubMedCentral
40.
Chang Y-L, Chen T-F, Shih Y-C, Chiu M-J, Yan S-H, Tseng WY (2015) Regional cingulum disruption, not gray matter atrophy, detects cognitive changes in amnestic mild cognitive impairment subtypes. J Alzheimers Dis JAD 44:125–138PubMed
41.
Verhage F (1964) Intelligentie en leeftijd: onderzoek bij Nederlanders van twaalf tot zevenenzeventig jaar [intelligence and age: research on Dutch people aged twelve to seventy-seven years old]. Van Gorcum, Assen
42.
Papma JM, de Groot M, de Koning I et al (2014) Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment. Hum Brain Mapp 35:2836–2851CrossRefPubMed
43.
de Boer R, Vrooman HA, van der Lijn F et al (2009) White matter lesion extension to automatic brain tissue segmentation on MRI. Neuroimage 45:1151–1161CrossRefPubMed
44.
Vrooman HA, Cocosco CA, van der Lijn F et al (2007) Multi-spectral brain tissue segmentation using automatically trained k-Nearest-Neighbor classification. Neuroimage 37:71–81CrossRefPubMed
45.
den Heijer T, van der Lijn F, Koudstaal PJ et al (2010) A 10-year follow-up of hippocampal volume on magnetic resonance imaging in early dementia and cognitive decline. Brain 133:1163–1172CrossRef
46.
van der Lijn F, den Heijer T, Breteler MMB, Niessen WJ (2008) Hippocampus segmentation in MR images using atlas registration, voxel classification, and graph cuts. Neuroimage 43:708–720CrossRefPubMed
47.
Bastos Leite AJ, van Straaten EC, Scheltens P, Lycklama G, Barkhof F (2004) Thalamic lesions in vascular dementia: low sensitivity of fluid-attenuated inversion recovery (FLAIR) imaging. Stroke 35:415–419CrossRefPubMed
48.
Wakana S, Caprihan A, Panzenboeck MM et al (2007) Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage 36:630–644CrossRefPubMedPubMedCentral
49.
Wakana S, Jiang H, Nagae-Poetscher LM, Van Zijl PCM, Mori S (2004) Fiber tract–based atlas of human white matter anatomy 1. Radiology 230:77–87CrossRefPubMed
50.
de Groot M, Vernooij MW, Klein S et al (2013) Improving alignment in Tract-based spatial statistics: evaluation and optimization of image registration. Neuroimage 76:400–411CrossRefPubMed
51.
Daselaar S, Veltman DJ, Rombouts S, Raaijmakers JGW, Jonker C (2003) Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects. Brain 126:43–56CrossRefPubMed
52.
Snodgrass JG, Corwin J (1988) Pragmatics of measuring recognition memory: applications to dementia and amnesia. J Exp Psychol Gen 117:34CrossRefPubMed
53.
Price CJ, Friston KJ (1999) Scanning patients with tasks they can perform. Hum Brain Mapp 8:102–108CrossRefPubMed
54.
Mundfrom DJ, Perrett JJ, Schaffer J, Piccone A, Roozeboom M (2006) Bonferroni adjustments in tests for regression coefficients. Multiple Linear Regression Viewpoints 32:1–6
55.
Celone KA, Calhoun VD, Dickerson BC et al (2006) Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis. J Neurosci 26:10222–10231CrossRefPubMed
56.
Jin G, Li K, Hu Y et al (2011) Amnestic mild cognitive impairment: functional MR imaging study of response in posterior cingulate cortex and adjacent precuneus during problem-solving tasks. Radiology 261:525–533CrossRefPubMed
57.
Dunn CJ, Duffy SL, Hickie IB et al (2014) Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment. NeuroImage: Clin 4:473–480CrossRef
58.
Miettinen PS, Pihlajamäki M, Jauhiainen AM et al (2011) Structure and function of medial temporal and posteromedial cortices in early Alzheimer’s disease. Eur J Neurosci 34:320–330CrossRefPubMed
59.
Villain N, Desgranges B, Viader F et al (2008) Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer's disease. J Neurosci 28:6174–6181CrossRefPubMedPubMedCentral
60.
Choo ILH, Lee DY, Oh JS et al (2010) Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 31:772–779CrossRefPubMed
61.
Zhang Y, Schuff N, Jahng GH et al (2007) Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology 68:13–19CrossRefPubMedPubMedCentral
62.
Jones-Gotman M, Zatorre RJ, Olivier A et al (1997) Learning and retention of words and designs following excision from medial or lateral temporal-lobe structures. Neuropsychologia 35:963–973CrossRefPubMed
63.
Kennepohl S, Sziklas V, Garver KE, Wagner DD, Jones-Gotman M (2007) Memory and the medial temporal lobe: hemispheric specialization reconsidered. Neuroimage 36:969–978CrossRefPubMed
64.
Terry DP, Sabatinelli D, Puente AN, Lazar NA, Miller LS (2015) A meta‐analysis of fMRI activation differences during episodic memory in Alzheimer's disease and mild cognitive impairment. J Neuroimaging 25:849–860CrossRefPubMed
65.
Tomadesso C, Perrotin A, Mutlu J et al (2015) Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment. NeuroImage: Clinical
66.
Dannhauser TM, Shergill SS, Stevens T et al (2008) An fMRI study of verbal episodic memory encoding in amnestic mild cognitive impairment. Cortex 44:869–880CrossRefPubMed
67.
Trivedi MA, Murphy CM, Goetz C et al (2008) fMRI activation changes during successful episodic memory encoding and recognition in amnestic mild cognitive impairment relative to cognitively healthy older adults. Dement Geriatr Cogn Disord 26:123–137CrossRefPubMedPubMedCentral
68.
Huijbers W, Mormino EC, Schultz AP et al (2015) Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain:awv007
69.
De Souza LC, Corlier F, Habert M-O et al (2011) Similar amyloid-β burden in posterior cortical atrophy and Alzheimer's disease. Brain 134:2036–2043CrossRefPubMed
70.
Chang YT, Huang CW, Chang YH et al (2015) Amyloid burden in the hippocampus and default mode network: relationships with gray matter volume and cognitive performance in mild stage Alzheimer disease. Medicine (Baltimore) 94:e763CrossRefPubMedCentral
71.
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42:631–639CrossRefPubMed
72.
Ingelsson M, Fukumoto H, Newell KL et al (2004) Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology 62:925–931CrossRefPubMed
73.
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63:38–46CrossRefPubMed
74.
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed
75.
Delacourte A, David JP, Sergeant N et al (1999) The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology 52:1158–1158CrossRefPubMed
76.
DeCarli C, Frisoni GB, Clark CM et al (2007) Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol 64:108–115CrossRefPubMed
77.
Schmidtke K, Hermeneit S (2008) High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI patients. Int Psychogeriatr 20:96–108CrossRefPubMed
78.
Sarazin M, Berr C, De Rotrou J et al (2007) Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology 69:1859–1867CrossRefPubMed
79.
Fischer P, Jungwirth S, Zehetmayer S et al (2007) Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology 68:288–291CrossRefPubMed
Metadata
Title
The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment
Authors
Janne M. Papma
Marion Smits
Marius de Groot
Francesco U. Mattace Raso
Aad van der Lugt
Henri A. Vrooman
Wiro J. Niessen
Peter J. Koudstaal
John C. van Swieten
Frederik M. van der Veen
Niels D. Prins
Publication date
01-09-2017
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 9/2017
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-017-4768-1

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