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Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Published online by Cambridge University Press:  05 March 2020

Margaret Abraham ,
Michael Seidenberg ,
Dana A. Kelly ,
Kristy A. Nielson ,
John L. Woodard ,
J. Carson Smith ,
Sally Durgerian  and
Stephen M. Rao
Margaret Abraham
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Michael Seidenberg
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Dana A. Kelly
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Kristy A. Nielson
Affiliation:
Department of Psychology, Marquette University, Milwaukee, WI53226, USA Department of Neurology, Medical College of Wisconsin, Milwaukee, WI53226, USA
John L. Woodard
Affiliation:
Department of Psychology, Wayne State University, Detroit, MI48202, USA
J. Carson Smith
Affiliation:
Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD20740, USA
Sally Durgerian
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI53226, USA
Stephen M. Rao*
Affiliation:
Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH44195, USA
*
*Correspondence and reprint requests to: Stephen M. Rao, PhD, Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue/U10, Cleveland, OH44195, USA, E-mail: raos2@ccf.org
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Abstract

Objective:

The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.

Methods:

Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.

Results:

At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.

Conclusions:

Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

Keywords

Mild cognitive impairmentAlzheimer diseaseRisk factorsMRIHippocampusLongitudinal studies

Information

Type
Brief Communication
Information
Journal of the International Neuropsychological Society , Volume 26 , Issue 7 , August 2020 , pp. 733 - 738
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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References

Baumgart, M., Snyder, H.M., Carrillo, M.C., Fazio, S., Kim, H., & Johns, H. (2015). Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dementia, 11(6), 718–726. doi: 10.1016/j.jalz.2015.05.016CrossRefGoogle ScholarPubMed
Carlesimo, G.A., Piras, F., Orfei, M.D., Iorio, M., Caltagirone, C., & Spalletta, G. (2015). Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer’s disease. Alzheimers Dementia (Amsterdam), 1(1), 24–32. doi: 10.1016/j.dadm.2014.12.001Google ScholarPubMed
Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., & Pericak-Vance, M.A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261(5123), 921–923. doi: 10.1126/science.8346443CrossRefGoogle ScholarPubMed
Evans, T.E., Adams, H.H.H., Licher, S., Wolters, F.J., van der Lugt, A., Ikram, M.K., & Ikram, M.A. (2018). Subregional volumes of the hippocampus in relation to cognitive function and risk of dementia. Neuroimage, 178, 129–135. doi: 10.1016/j.neuroimage.2018.05.041CrossRefGoogle ScholarPubMed
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. doi: 10.1016/0022-3956(75)90026-6CrossRefGoogle ScholarPubMed
Fouquet, M., Besson, F.L., Gonneaud, J., La Joie, R., & Chételat, G. (2014). Imaging brain effects of APOE4 in cognitively normal individuals across the lifespan. Neuropsychology Review, 24(3), 290–299. doi: 10.1007/s11065-014-9263-8CrossRefGoogle ScholarPubMed
Haller, S., Montandon, M.L., Rodriguez, C., Ackermann, M., Herrmann, F.R., & Giannakopoulos, P. (2017). APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline. American Journal of Neuroradiology, 38(7), 1335–1342. doi: 10.3174/ajnr.A5184CrossRefGoogle ScholarPubMed
Hanseeuw, B.J., Van Leemput, K., Kavec, M., Grandin, C., Seron, X., & Ivanoiu, A. (2011). Mild cognitive impairment: differential atrophy in the hippocampal subfields. American Journal of Neuroradiology, 32(9), 1658–1661. doi: 10.3174/ajnr.A2589CrossRefGoogle ScholarPubMed
Iglesias, J.E., Augustinack, J.C., Nguyen, K., Player, C.M., Player, A., Wright, M., Roy, N., Frosch, M.P., McKee, A.C., Wald, L.L., Fischl, B., Von Leemput, K., & The Alzheimer’s Disease Neuroimaging Initiative (2015). A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI. Neuroimage, 115, 117–137. doi: 10.1016/j.neuroimage.2015.04.042CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Knopman, D.S., Jagust, W.J., Shaw, L.M., Aisen, P.S., Weiner, M.W., Petersen, R.C., & Trojanowski, J.Q. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9(1), 119–128. doi: 10.1016/s1474-4422(09)70299-6CrossRefGoogle ScholarPubMed
Jurica, P.J., Leitten, C.L., & Mattis, S. (2001). DRS-2 Dementia Rating Scale-2: Professional Manual. Lutz, FL: Psychological Assessment Resources.Google Scholar
Lawton, M.P., & Brody, E.M. (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist, 9(3), 179–186.CrossRefGoogle ScholarPubMed
O’Donoghue, M.C., Murphy, S.E., Zamboni, G., Nobre, A.C., & Mackay, C.E. (2018). APOE genotype and cognition in healthy individuals at risk of Alzheimer’s disease: a review. Cortex, 104, 103–123. doi: 10.1016/j.cortex.2018.03.025CrossRefGoogle ScholarPubMed
Price, J.L., & Morris, J.C. (1999). Tangles and plaques in non-demented aging and “preclinical” Alzheimer’s disease. Annals of Neurology, 45, 358–368. doi: 10.1002/1531-8249(199903)45:3<358:AID-ANA12>3.0.CO;2-X3.0.CO;2-X>CrossRefGoogle Scholar
Qian, J., Wolters, F.J., Beiser, A., Haan, M., Ikram, M.A., Karlawish, J., & Blacker, D. (2017). APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts. PLoS Medicine, 14(3), e1002254. doi: 10.1371/journal.pmed.1002254CrossRefGoogle ScholarPubMed
Rao, S.M., Bonner-Jackson, A., Nielson, K.A., Seidenberg, M., Smith, J.C., Woodard, J.L., & Durgerian, S. (2015). Genetic risk for Alzheimer’s disease alters the 5-year trajectory of semantic memory activation in cognitively intact elders. Neuroimage, 111, 136–146.CrossRefGoogle ScholarPubMed
Rey, A. (1958). L’examen clinique en psychologie. Paris: Presses Universitaires de France.Google Scholar
Schmidt, M. (1996). Rey Auditory And Verbal Learning Test: A Handbook. Los Angeles: Western Psychological Services.Google Scholar
Schmidt, K.S. (2004). Dementia Rating Scale-2 Alternate Form: Manual Supplement. Lutz, FL: Psychological Assessment Resources.Google Scholar
Seidenberg, M., Guidotti, L., Nielson, K.A., Woodard, J.L., Durgerian, S., Antuono, P., & Rao, S.M. (2009). Semantic memory activation in individuals at risk for developing Alzheimer disease. Neurology, 73(8), 612–620. doi: 10.1212/WNL.0b013e3181b389adCrossRefGoogle ScholarPubMed
Stonnington, C.M., Chen, Y., Savage, C.R., Lee, W., Bauer, R.J. III, Sharieff, S., Thiyyagura, P., Alexander, G.E., Caselli, R.J., Locke, D.E.C., Reiman, E.M., & Chen, K. (2018). Predicting imminent progression to clinically significant memory decline using volumetric MRI and FDG PET. Journal of Alzheimer's Disease, 63(2), 603–615. doi: 10.3233/JAD-170852CrossRefGoogle ScholarPubMed
Sundermann, E.E., Maki, P., Biegon, A., Lipton, R.B., Mielke, M.M., Machulda, M., Bondi, M.W., & Alzheimer’s Disease Neuroimaging Initiative (2019). Sex-specific norms for verbal memory tests may improve diagnostic accuracy of amnestic MCI. Neurology, 93(20), e1881–e1889.Google ScholarPubMed
Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M., & Leirer, V.O. (1982). Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research, 17(1), 37–49. doi: 10.1016/0022-3956(82)90033-4CrossRefGoogle ScholarPubMed