This study aims to predict cognitive decline using a performance endophenotype of neuro-feedback based on functional magnetic resonance imaging in real time in a population at risk for Alzheimer's disease (AD).

In this research project, a longitudinal study in a healthy population that is under increased risk of developing AD will be performed. It is anticipated that some of the participating subjects will develop episodic memory decline within this longitudinal follow-up. The memory binding Test (MBT) and/or the Free and Cued Selective Reminding Test (FCSRT), the most accurate and reliable available episodic memory tests, are going to be performed by the subjects at multiple longitudinal data collection points. The project proposes to develop a real-time functional magnetic resonance imaging (rtfMRI) task, and to test whether the subjects' performance on the task can predict the apparition of cognitive decline. The impact of other relevant biomarkers by adding them to the model: age, gender, number of APOE-e4 alleles, cognitive scores, cerebrospinal fluid (CSF) biomarkers, amyloid Positron Emission Tomography (PET), lifestyle habits and clinical background will be studied.

Inclusion Criteria:

• Adult men and women (aged 45-75) that have participated in the study 45-65/FPM2012.
• Persons that accept the study's test and procedures that are as follows: magnetic resonance imaging and neuropsychological tests.
• Signature of the study's informed consent form, accepting to not receive information with regards to any research results that are not clinically relevant.

Exclusion Criteria:

• Any contraindication to MRI (e.g. pacemaker, claustrophobia, etc.)
• Any condition that according to the investigator's judgement could interfere with the proper execution of the study's procedures and/or its follow-up.

Participating subjects are healthy adults (aged 45-75 at inclusion) already recruited within the ALFA study (http://clinicaltrials.gov/ct2/show/NCT01835717; Estudi 45-65 FPM/2012).