Early indications of future cognitive decline: stable versus declining controls

Angela Rizk-Jackson, Philip Insel, Ronald Petersen, Paul Aisen, Clifford Jack, Michael Weiner, Angela Rizk-Jackson, Philip Insel, Ronald Petersen, Paul Aisen, Clifford Jack, Michael Weiner

Abstract

This study aimed to identify baseline features of normal subjects that are associated with subsequent cognitive decline. Publicly available data from the Alzheimer's Disease Neuroimaging Initiative was used to find differences in baseline clinical assessments (ADAScog, AVLT, FAQ) between cognitively healthy individuals who will suffer cognitive decline within 48 months and those who will remain stable for that period. Linear regression models indicated an individual's conversion status was significantly associated with certain baseline neuroimaging measures, including posterior cingulate glucose metabolism. Linear Discriminant Analysis models built with baseline features derived from MRI and FDG-PET measures were capable of successfully predicting whether an individual will convert to MCI within 48 months or remain cognitively stable. The findings from this study support the idea that there exist informative differences between normal people who will later develop cognitive impairments and those who will remain cognitively stable for up to four years. Further, the feasibility of developing predictive models that can detect early states of cognitive decline in seemingly normal individuals was demonstrated.

Conflict of interest statement

Competing Interests: The authors have the following interests. Dr. Weiner has served on scientific advisory boards for Eli Lilly, Araclon, Biogen Idec and Pfizer; has served as a consultant to Astra Zeneca, Araclon, Medivation/Pfizer, Ipsen, TauRx Therapeutics Ltd, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, Servier, Synarc, Janssen, and KLJ Associates; has received funding for travel from NeuroVigil Inc, Siemens, AstraZeneca, Eli Lilly, Ipsen, Novartis, and Travel eDreams, Inc; has received honoraria from NeuroVigil, Inc, has received research support from Merck and Avid; and has stock options for Synarc and Elan. This does not alter their adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Distribution of scores on clinical…
Figure 1. Distribution of scores on clinical assessments for converters and non-converters at baseline visit.
A) Boxplot and mean with 95% CIs showing scores on the ADAS-cognitive test. B) Boxplot and mean with 95% CIs showing scores on the AVLT test. C) Bar graph showing scores on the FAQ assessment.
Figure 2. ROC curve displaying performance of…
Figure 2. ROC curve displaying performance of predictive models built using subsets of data including clinical measures, MRI-derived features, PET-derived features, and MRI-PET combined feature sets.

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