Comparing predictors of conversion and decline in mild cognitive impairment

S. M. Landau, D. Harvey, C. M. Madison, E. M. Reiman, N. L. Foster, P. S. Aisen, R. C. Petersen, L. M. Shaw, J. Q. Trojanowski, C. R. Jack, M. W. Weiner, W. J. Jagust
2010 Neurology  
Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods: APOE ⑀4 allele frequency, CSF proteins (A␤ 1-42 , total tau, hyperphosphorylated tau [p-tau 181p ]), glucose metabolism
more » ... PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n ϭ 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 Ϯ 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p Յ 0.02). In addition, the CSF ratio p-tau 181p /A␤ 1-42 (␤ ϭ 1.10 Ϯ 0.53; p ϭ 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau 181p /A␤ 1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention. Neurology ® 2010;75:230 -238 GLOSSARY AD ϭ Alzheimer disease; ADAS-Cog ϭ Alzheimer's Disease Assessment Scale-Cognitive Subscale; ADNI ϭ Alzheimer's Disease Neuroimaging Initiative; AVLT ϭ Auditory Verbal Learning Test; CDR ϭ Clinical Dementia Rating; CI ϭ confidence interval; FDG ϭ [ 18 F]fluorodeoxyglucose; MCI ϭ mild cognitive impairment; MNI ϭ Montreal Neurological Institute; p-tau 181p ϭ hyperphosphorylated tau; ROC ϭ receiver operating characteristic; t-tau ϭ total tau. e-Pub ahead of print on June 30, 2010, at From the Helen Wills Neuroscience Institute (S.M.L., C.M.M., W.J.J.),
doi:10.1212/wnl.0b013e3181e8e8b8 pmid:20592257 pmcid:PMC2906178 fatcat:tc3wtbv53bdrpkw3hgeev3knfi