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A multivariate model of time to conversion from mild cognitive impairment to Alzheimer’s disease

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Abstract

The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the “progressive” MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) the “stable” MCI group (n = 75; mean time of follow-up 31.37 ± 14.58 months). Kaplan–Meier survival analyses were applied to explore each variable’s relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were “unfavorable” (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.

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Funding

This study was supported by two projects (PSI2009-14415-C03-01 and PSI2012-38375-C03-01) and by a post-doctoral fellowship to Pablo Cuesta (IJC2018-038404-I) from the Spanish Ministry of Economy and Competitiveness.

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Authors and Affiliations

  1. Department of Experimental Psychology, Cognitive Processes and Speech Therapy, Complutense University of Madrid, Madrid, Spain

    María Eugenia López, Pablo Cuesta & Fernando Maestú

  2. Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Polytechnic University of Madrid, Madrid, Spain

    María Eugenia López, Pablo Cuesta, Inmaculada Concepción Rodríguez-Rojo, Fernando Maestú & Alberto Fernández

  3. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain

    María Eugenia López & Fernando Maestú

  4. Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain

    María Eugenia López, Agustín Turrero, Ana Barabash, Alberto Marcos, Fernando Maestú & Alberto Fernández

  5. Department of Statistics and Operational Research, Complutense University of Madrid, Madrid, Spain

    Agustín Turrero

  6. Psychology Faculty, Centro Universitario Villanueva, Madrid, Spain

    Inmaculada Concepción Rodríguez-Rojo

  7. Physiotherapy and Nursing Faculty, University of Castilla-La Mancha, Toledo, Spain

    Inmaculada Concepción Rodríguez-Rojo

  8. Laboratory of Psychoneuroendocrinology and Genetics, San Carlos University Hospital, Madrid, Spain

    Ana Barabash

  9. Neurology Department, San Carlos University Hospital, Madrid, Spain

    Alberto Marcos

  10. Department of Legal Medicine, Psychiatry and Pathology, Complutense University of Madrid, Madrid, Spain

    Alberto Fernández

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  1. María Eugenia López
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  3. Pablo Cuesta
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Correspondence to María Eugenia López.

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López, M.E., Turrero, A., Cuesta, P. et al. A multivariate model of time to conversion from mild cognitive impairment to Alzheimer’s disease. GeroScience 42, 1715–1732 (2020). https://doi.org/10.1007/s11357-020-00260-7

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