Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer's disease

doi:10.1007/s11682-018-0019-6

. 2020 Jun;14(3):787-796.

doi: 10.1007/s11682-018-0019-6.

Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer's disease

Eero Vuoksimaa¹, Linda K McEvoy², Dominic Holland³, Carol E Franz^{4

5}, William S Kremen^{4

5

6}, Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, P.O. Box 20 (Tukholmankatu 8), 00014, Helsinki, Finland. [email protected].
² Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
³ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁵ Center for Behavior Genetics of Aging, University of California, San Diego, CA, USA.
⁶ Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.

PMID: 30511118
PMCID: PMC7275013
DOI: 10.1007/s11682-018-0019-6

Free PMC article

Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer's disease

Eero Vuoksimaa et al. Brain Imaging Behav. 2020 Jun.

Free PMC article

. 2020 Jun;14(3):787-796.

doi: 10.1007/s11682-018-0019-6.

Authors

Eero Vuoksimaa¹, Linda K McEvoy², Dominic Holland³, Carol E Franz^{4

5}, William S Kremen^{4

5

6}, Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, P.O. Box 20 (Tukholmankatu 8), 00014, Helsinki, Finland. [email protected].
² Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
³ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁵ Center for Behavior Genetics of Aging, University of California, San Diego, CA, USA.
⁶ Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.

PMID: 30511118
PMCID: PMC7275013
DOI: 10.1007/s11682-018-0019-6

Abstract

Mild cognitive impairment (MCI) is a heterogeneous condition with variable outcomes. Improving diagnosis to increase the likelihood that MCI reliably reflects prodromal Alzheimer's Disease (AD) would be of great benefit for clinical practice and intervention trials. In 230 cognitively normal (CN) and 394 MCI individuals from the Alzheimer's Disease Neuroimaging Initiative, we studied whether an MCI diagnostic requirement of impairment on at least two episodic memory tests improves 3-year prediction of medial temporal lobe atrophy and progression to AD. Based on external age-adjusted norms for delayed free recall on the Rey Auditory Verbal Learning Test (AVLT), MCI participants were further classified as having normal (AVLT+, above -1 SD, n = 121) or impaired (AVLT -, -1 SD or below, n = 273) AVLT performance. CN, AVLT+, and AVLT- groups differed significantly on baseline brain (hippocampus, entorhinal cortex) and cerebrospinal fluid (amyloid, tau, p-tau) biomarkers, with the AVLT- group being most abnormal. The AVLT- group had significantly more medial temporal atrophy and a substantially higher AD progression rate than the AVLT+ group (51% vs. 16%, p < 0.001). The AVLT+ group had similar medial temporal trajectories compared to CN individuals. Results were similar even when restricted to individuals with above average (based on the CN group mean) baseline medial temporal volume/thickness. Requiring impairment on at least two memory tests for MCI diagnosis can markedly improve prediction of medial temporal atrophy and conversion to AD, even in the absence of baseline medial temporal atrophy. This modification constitutes a practical and cost-effective approach for clinical and research settings.

Keywords: Alzheimer’s disease; Biomarkers; Early detection; Mild cognitive impairment; Neuropsychological testing.

Conflict of interest statement

Dr. McEvoy has stock options in CorTechs Labs, Inc.

Figures

**Fig. 1**
Baseline cerebrospinal fluid levels of β-amyloid (ABETA142), total tau (TAU) and phosphorylated tau (PTAU181). a Means with 95% confidence intervals in cognitively normal participants (CN) and in those with amnestic mild cognitive impairment either with good (aMCI AVLT+) or impaired (aMCI AVLT-) Auditory Verbal Learning Test performance. * = statistically significant (p < 0.05) difference between groups. b scatterplot of β-amyloid and total tau in CN group, c scatterplot of β-amyloid and total tau in the aMCI AVLT+ group, d scatterplot of β-amyloid and total tau in the aMCI AVLT- group, with cutoff values from Shaw et al. , 65, 403–413 Annals of Neurology

**Fig. 2**
Volume change as a proportion of baseline size from 6 to 36 months in cognitively normal participants (CN) and in those with amnestic mild cognitive impairment with normal (aMCI AVLT+) or impaired (aMCI AVLT-) Auditory Verbal Learning Test performance for hippocampus (HV; panel a) and entorhinal cortex (ECV, panel b)

**Fig. 3**
Kaplan-Meier survival estimates in individuals with amnestic mild cognitive impairment either with good (aMCI AVLT+) or impaired (aMCI AVLT-) Rey Auditory Verbal Learning Test performance

See this image and copyright information in PMC

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References

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1. Apostolova, L. G., Morra, J. H., Green, A. E., Hwang, K. S., Avedissian, C., Woo, E., .... Alzheimer’s Disease Neuroimaging Initiative. (2010). Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects. NeuroImage, 51(1), 488–499. 10.1016/j.neuroimage.2009.12.125 - PMC - PubMed
1. Bondi, M. W., Edmonds, E. C., Jak, A. J., Clark, L. R., Delano-Wood, L., McDonald, C. R., ... Salmon, D. P. (2014). Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. Journal of Alzheimer's Disease : JAD, 42(1), 275–289. 10.3233/JAD-140276. - PMC - PubMed
1. Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology and Experimental Neurology. 2011;70(11):960–969. doi: 10.1097/NEN.0b013e318232a379. - DOI - PubMed
1. Chang, Y. L., Bondi, M. W., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Jr, Jacobson, M. W., ... Alzheimer’s Disease Neuroimaging Initiative. (2010). Brain substrates of learning and retention in mild cognitive impairment diagnosis and progression to Alzheimer’s disease. Neuropsychologia, 48(5), 1237–1247. 10.1016/j.neuropsychologia.2009.12.024. - PMC - PubMed

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[1] Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., ... Phelps, C. H. (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. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 7(3), 270–279. 10.1016/j.jalz.2011.03.008. - PMC - PubMed

[2] Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., ... Phelps, C. H. (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. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 7(3), 270–279. 10.1016/j.jalz.2011.03.008. - PMC - PubMed

[3] Apostolova, L. G., Morra, J. H., Green, A. E., Hwang, K. S., Avedissian, C., Woo, E., .... Alzheimer’s Disease Neuroimaging Initiative. (2010). Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects. NeuroImage, 51(1), 488–499. 10.1016/j.neuroimage.2009.12.125 - PMC - PubMed

[4] Apostolova, L. G., Morra, J. H., Green, A. E., Hwang, K. S., Avedissian, C., Woo, E., .... Alzheimer’s Disease Neuroimaging Initiative. (2010). Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects. NeuroImage, 51(1), 488–499. 10.1016/j.neuroimage.2009.12.125 - PMC - PubMed

[5] Bondi, M. W., Edmonds, E. C., Jak, A. J., Clark, L. R., Delano-Wood, L., McDonald, C. R., ... Salmon, D. P. (2014). Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. Journal of Alzheimer's Disease : JAD, 42(1), 275–289. 10.3233/JAD-140276. - PMC - PubMed

[6] Bondi, M. W., Edmonds, E. C., Jak, A. J., Clark, L. R., Delano-Wood, L., McDonald, C. R., ... Salmon, D. P. (2014). Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. Journal of Alzheimer's Disease : JAD, 42(1), 275–289. 10.3233/JAD-140276. - PMC - PubMed

[7] Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology and Experimental Neurology. 2011;70(11):960–969. doi: 10.1097/NEN.0b013e318232a379. - DOI - PubMed

[8] Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology and Experimental Neurology. 2011;70(11):960–969. doi: 10.1097/NEN.0b013e318232a379. - DOI - PubMed

[9] Chang, Y. L., Bondi, M. W., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Jr, Jacobson, M. W., ... Alzheimer’s Disease Neuroimaging Initiative. (2010). Brain substrates of learning and retention in mild cognitive impairment diagnosis and progression to Alzheimer’s disease. Neuropsychologia, 48(5), 1237–1247. 10.1016/j.neuropsychologia.2009.12.024. - PMC - PubMed

[10] Chang, Y. L., Bondi, M. W., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Jr, Jacobson, M. W., ... Alzheimer’s Disease Neuroimaging Initiative. (2010). Brain substrates of learning and retention in mild cognitive impairment diagnosis and progression to Alzheimer’s disease. Neuropsychologia, 48(5), 1237–1247. 10.1016/j.neuropsychologia.2009.12.024. - PMC - PubMed

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