Prediction of Alzheimer disease in subjects with amnestic and nonamnestic MCI

Stephanie J B Vos, Ineke A. Van Rossum, Frans Verhey, Dirk L. Knol, Hilkka Soininen, Lars Olof Wahlund, Harald Hampel, Magda Tsolaki, Lennart Minthon, Giovanni B. Frisoni, Lutz Froelich, Flavio Nobili, Wiesje Van Der Flier, Kaj Blennow, Robin Wolz, Philip Scheltens, Pieter Jelle Visser

Research output: Contribution to journalArticlepeer-review


Objective: To compare the predictive accuracy of β-amyloid (Aβ)1-42 and total tau in CSF, hippocampal volume (HCV), and APOE genotype for Alzheimer disease (AD)-type dementia in subjects with amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI). Methods: We selected 399 subjects with aMCI and 226 subjects with naMCI from a multicenter memory clinic-based cohort. We measured CSF Aβ1-42 and tau by ELISA (n = 231), HCV on MRI (n = 388), and APOE e4 (n = 523). Follow-up was performed annually up to 5 years. Outcome measures were progression to AD-type dementia and cognitive decline. Results: At least 1 follow-up was available for 538 subjects (86%). One hundred thirty-two subjects with aMCI (38%) and 39 subjects with naMCI (20%) progressed to AD-type dementia after an average follow-up of 2.5 years. CSF Aβ1-42, tau, Aβ1-42/tau ratio, HCV, and APOE e4 predicted AD-type dementia in each MCI subgroup with the same overall diagnostic accuracy. However, CSF Aβ1-42 concentration was higher and hippocampal atrophy less severe in subjects with naMCI compared with aMCI. This reduced the sensitivity but increased the specificity of these markers for AD-type dementia in subjects with naMCI. Conclusions: AD biomarkers are useful to predict AD-type dementia in subjects with aMCI and naMCI. However, biomarkers might not be as sensitive for early diagnosis of AD in naMCI compared with aMCI. This may have implications for clinical implementation of the National Institute on Aging and Alzheimer's Association criteria.

Original languageEnglish
Pages (from-to)1124-1132
Number of pages9
Issue number12
Publication statusPublished - Mar 19 2013

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)


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