Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-06-2016 | Original Article

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment

Authors: Eun Hyun Seo, IL Han Choo, For the Alzheimer’s Disease Neuroimaging Initiative

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2016

Abstract

Purpose

Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer’s disease (AD), i.e., aMCI with low beta-amyloid (Aβ) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aβ burden negative (aMCI-Aβ−) and to compare these results with aMCI with Aβ burden positive (aMCI-Aβ+).

Methods

Individuals with aMCI (n = 498) were selected from the Alzheimer’s Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aβ− or aMCI-Aβ+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model.

Results

For aMCI-Aβ−, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aβ+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate

Conclusion

Our findings indicate that memory impairment in aMCI-Aβ− is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aβ+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aβ burden level.

Patricio CM, Gabriela C, Julieta RM, Marcos FS, Federico N, Griselda R, et al. Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen 2015;30(6):599–606. doi:10.1177/1533317515576387.CrossRefPubMed

Nettiksimmons J, DeCarli C, Landau S, Beckett L. Alzheimer’s Disease Neuroimaging Initiative. Biological heterogeneity in ADNI amnestic mild cognitive impairment. Alzheimers Dement 2014;10(5):511–21.e1. doi:10.1016/j.jalz.2013.09.003.CrossRefPubMedPubMedCentral

Vos SJ, van Rossum IA, Verhey F, Knol DL, Soininen H, Wahlund LO, et al. Prediction of Alzheimer disease in subjects with amnestic and nonamnestic MCI. Neurology 2013;80(12):1124–32. doi:10.1212/WNL.0b013e318288690c.CrossRefPubMed

Alichniewicz KK, Brunner F, Klünemann HH, Greenlee MW. Structural and functional neural correlates of visuospatial information processing in normal aging and amnestic mild cognitive impairment. Neurobiol Aging 2012;33(12):2782–97. doi:10.1016/j.neurobiolaging.2012.02.010.CrossRefPubMed

Brugnolo A, Morbelli S, Arnaldi D, De Carli F, Accardo J, Bossert I, et al. Metabolic correlates of Rey auditory verbal learning test in elderly subjects with memory complaints. J Alzheimers Dis 2014;39(1):103–13. doi:10.3233/JAD-121684.PubMed

Dos Santos V, Thomann PA, Wüstenberg T, Seidl U, Essig M, Schröder J. Morphological cerebral correlates of CERAD test performance in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 2011;23(3):411–20. doi:10.3233/JAD-2010-100156.PubMed

Leube DT, Weis S, Freymann K, Erb M, Jessen F, Heun R, et al. Neural correlates of verbal episodic memory in patients with MCI and Alzheimer’s disease--a VBM study. Int J Geriatr Psychiatry 2008;23(11):1114–8. doi:10.1002/gps.2036.CrossRefPubMed

Schönknecht OD, Hunt A, Toro P, Henze M, Haberkorn U, Schröder J. Neural correlates of delayed episodic memory in patients with mild cognitive impairment--a FDG PET study. Neurosci Lett 2009;467(2):100–4. doi:10.1016/j.neulet.2009.10.014.CrossRefPubMed

Schwindt GC, Black SE. Functional imaging studies of episodic memory in Alzheimer’s disease: a quantitative meta-analysis. Neuroimage 2009;45(1):181–90. doi:10.1016/j.neuroimage.2008.11.024.CrossRefPubMed

10.

Jueptner M, Weiller C. Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI. Neuroimage 1995;2(2):148–56. doi:S1053811985710178 [pii].CrossRefPubMed

11.

Sokoloff L. Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. Fed Proc 1981;40(8):2311–6.PubMed

12.

Della Rosa PA, Cerami C, Gallivanone F, Prestia A, Caroli A, Castiglioni I, et al. A standardized [18F]-FDG-PET template for spatial normalization in statistical parametric mapping of dementia. Neuroinformatics 2014;12(4):575–93. doi:10.1007/s12021-014-9235-4.CrossRefPubMed

13.

Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995;36(7):1238–48.PubMed

14.

Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 1997;42(1):85–94. doi:10.1002/ana.410420114.CrossRefPubMed

15.

Perani D. FDG-PET and amyloid-PET imaging: the diverging paths. Curr Opin Neurol 2014;27(4):405–13. doi:10.1097/WCO.0000000000000109.CrossRefPubMed

16.

Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 2010;74(3):201–9. doi:10.1212/WNL.0b013e3181cb3e25.CrossRefPubMedPubMedCentral

17.

Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43(11):2412–4.CrossRefPubMed

18.

Crane PK, Carle A, Gibbons LE, Insel P, Mackin RS, Gross A, et al. Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Brain Imaging Behavior 2012;6(4):502–16. doi:10.1007/s11682-012-9186-z.CrossRefPubMedPubMedCentral

19.

Pfeffer RI, Kurosaki TT, Harrah Jr CH, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37(3):323–9.CrossRefPubMed

20.

Teng E, Becker BW, Woo E, Knopman DS, Cummings JL, Lu PH. Utility of the functional activities questionnaire for distinguishing mild cognitive impairment from very mild Alzheimer disease. Alzheimer Dis Assoc Disord 2010;24(4):348–53. doi:10.1097/WAD.0b013e3181e2fc84.CrossRefPubMedPubMedCentral

21.

Landau SM, Mintun MA, Joshi AD, Koeppe RA, Petersen RC, Aisen PS, et al. Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol 2012;72(4):578–86. doi:10.1002/ana.23650.CrossRefPubMedPubMedCentral

22.

Jagust WJ, Bandy D, Chen K, Foster NL, Landau SM, Mathis CA, et al. The Alzheimer’s Disease Neuroimaging Initiative positron emission tomography core. Alzheimers Dement 2010;6(3):221–9. doi:10.1016/j.jalz.2010.03.003.CrossRefPubMedPubMedCentral

23.

Joshi A, Koeppe RA, Fessler JA. Reducing between scanner differences in multi-center PET studies. Neuroimage 2009;46(1):154–9. doi:10.1016/j.neuroimage.2009.01.057.CrossRefPubMedPubMedCentral

24.

Dukart J, Mueller K, Horstmann A, Vogt B, Frisch S, Barthel H, et al. Differential effects of global and cerebellar normalization on detection and differentiation of dementia in FDG-PET studies. Neuroimage 2010;49(2):1490–5. doi:10.1016/j.neuroimage.2009.09.017.CrossRefPubMed

25.

Park S, Tyszka JM, Allman JM. The claustrum and insula in Microcebus murinus: a high resolution diffusion imaging study. Front Neuroanat 2012;6:21. doi:10.3389/fnana.2012.00021.CrossRefPubMedPubMedCentral

26.

Torgerson CM, Irimia A, Goh SY, Van Horn JD. The DTI connectivity of the human claustrum. Hum Brain Mapp 2015;36(3):827–38. doi:10.1002/hbm.22667.CrossRefPubMedPubMedCentral

27.

Fernández-Miranda JC, Rhoton Jr AL, Kakizawa Y, Choi C, Alvarez-Linera J. The claustrum and its projection system in the human brain: a microsurgical and tractographic anatomical study. J Neurosurg 2008;108(4):764–74. doi:10.3171/JNS/2008/108/4/0764.CrossRefPubMed

28.

Naghavi HR, Eriksson J, Larsson A, Nyberg L. The claustrum/insula region integrates conceptually related sounds and pictures. Neurosci Lett 2007;422(1):77–80. doi:10.1016/j.neulet.2007.06.009.CrossRefPubMed

29.

Davis KD, Hutchison WD, Lozano AM, Tasker RR, Dostrovsky JO. Human anterior cingulate cortex neurons modulated by attention-demanding tasks. J Neurophysiol 2000;83(6):3575–7.PubMed

30.

Leech R, Sharp DJ. The role of the posterior cingulate cortex in cognition and disease. Brain 2014;137(Pt 1):12–32. doi:10.1093/brain/awt162.CrossRefPubMedPubMedCentral

31.

Posner MI, Rothbart MK. Attention, self-regulation and consciousness. Philos Trans R Soc Lond B Biol Sci 1998;353(1377):1915–27. doi:10.1098/rstb.1998.0344.CrossRefPubMedPubMedCentral

32.

Braskie MN, Small GW, Bookheimer SY. Entorhinal cortex structure and functional MRI response during an associative verbal memory task. Hum Brain Mapp 2009;30(12):3981–92. doi:10.1002/hbm.20823.CrossRefPubMedPubMedCentral

33.

Cabeza R, Nyberg L. Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 2000;12(1):1–47.CrossRefPubMed

34.

Wheeler ME, Buckner RL. Functional-anatomic correlates of remembering and knowing. Neuroimage 2004;21(4):1337–49. doi:10.1016/j.neuroimage.2003.11.001.CrossRefPubMed

35.

Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frölich L, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 2002;17(1):302–16.CrossRefPubMed

36.

Tulving E, Donaldson W, Bower GH. Research. USOoN. Organization of memory. New York: Academic Press; 1972.

37.

Cohen NJ, Squire LR. Preserved learning and retention of pattern-analyzing skill in amnesia: dissociation of knowing how and knowing that. Science 1980;210(4466):207–10.CrossRefPubMed

Title: Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment
Authors: Eun Hyun Seo
IL Han Choo
For the Alzheimer’s Disease Neuroimaging Initiative
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-015-3261-9

At a glance: The STEP trials

Springer Medicine

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2016

18F-DOPA: the versatile radiopharmaceutical

Current status of PET imaging in Huntington’s disease

Molecular imaging with 99mTc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison

In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

Imaging with 124I in differentiated thyroid carcinoma: is PET/MRI superior to PET/CT?

Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study