Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Multivariate Follow-Up Study

Article type: Research Article

Authors: López, María Eugenia^{a; b; c; *} | Turrero, Agustín^{c; d} | Cuesta, Pablo^b | López-Sanz, David^{b; e} | Bruña, Ricardo^b | Marcos, Alberto^{c; f} | Gil, Pedro^{c; g} | Yus, Miguel^{c; h} | Barabash, Ana^{c; i} | Cabranes, José Antonio^{c; i} | Maestú, Fernando^{b; c; e} | Fernández, Alberto^{b; c; j}

Affiliations: [a] Laboratory of Neuropsychology, Universitat de les Illes Balears, Palma de Mallorca, Spain | [b] Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain | [c] Institute of Sanitary Investigation [IdISSC], San Carlos University Hospital, Madrid, Spain | [d] Department of Biostatistics and Operational Investigation, Complutense University of Madrid, Spain | [e] Department of Basic Psychology II, Complutense University of Madrid, Spain | [f] Neurology Department, San Carlos University Hospital, Madrid, Spain | [g] Geriatrics Department, San Carlos University Hospital, Madrid, Spain | [h] Radiology Department, San Carlos University Hospital, Madrid, Spain | [i] Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, San Carlos University Hospital, Madrid, Spain | [j] Department of Psychiatry, Faculty of Medicine, Complutense University of Madrid, Spain

Correspondence: [*] Correspondence to: María Eugenia López, Laboratory of Neuropsychology, Universitat de les Illes Balears, Carr. de Valldemossa, km 7,5, CP. 07122 Palma de Mallorca, Islas Baleares, Spain; Laboratory of Cognitive and Computational Neuroscience (UCM-UPM), Centre for Biomedical Technology (CTB), Campus de Montegancedo s/n, 28223 Pozuelo de Alarcón, Madrid, Spain; Institute of Sanitary Investigation [IdISSC], San Carlos University Hospital, Madrid, Spain. E-mail: [email protected].

Abstract: Recent proposals of diagnostic criteria within the healthy aging-Alzheimer’s disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The “stable” MCI group (sMCI, 21 subjects) and the “progressive” MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as “first order” predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.

Keywords: Alzheimer’s disease, APOE, cognitive reserve, hippocampal volume, magnetoencephalography; mild cognitive impairment, neuropsychological tests, predictive model

DOI: 10.3233/JAD-151034

Journal: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 133-143, 2016