Study to understand factors related with the preclinical stages of Alzheimer's Disease and investigate markers that predict its progression.

Cross-sectional and single arm study performed on a subgroup of individuals recruited in the ALFA project.

Study without therapeutic interest for the research participants (440 participants of the ALFA project who have been selected for being cognitively healthy and in their vast majority are direct descendants of patients diagnosed with Alzheimer's Disease).

Each study candidate will be selected from the ALFA project (STUDY 45-65 FPM/2012) according to their clinical characteristics, their compliance to selection criteria and their desire to participate in this study.

After signing this study's specific informed consent form, the neuropsychological screening and the brain MRI acquisition will be performed. Once all inclusion criteria are checked, the PET scans with 18F-Flutemetamol and 18F-FDG will be performed

18F-Flutemetamol scans will be categorized as either positive or negative according to the standardized uptake value ratio (a quantitative measurement based on a ratio of mean target cortex activity divided by that in a cerebellar reference region). Participants with a SUVr over 1.56 will be classified as positive and, otherwise, as negative.

Inclusion Criteria:

• To sign the study informed consent form approved by the corresponding authorities.
• Men and women enrolled in the ALFA project (STUDY 45-65 FPM/2012).
• Participants with a cerebral MRI (magnetic resonance imaging) not suggestive of radiological incidental findings constituting an exclusion criterion.
• Cognition within psychometrically normal ranges: MMSE (Mini Mental State Examination ≥26 and Semantic Fluency (animals) ≥12.
• Score of 0 in the CDR scale (Clinical Dementia Rating).
• Good knowledge of the language and being literate.
• Female participants should be post-menopausal or present a negative pregnancy test at the moment of PET acquisition.

Exclusion Criteria:

• Present cognitive impairment.
• Presence of clinically relevant psychiatric disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR) criteria: major depressive disorder, generalized anxiety disorder, schizophrenia or bipolar disorder.
• Individuals with visual and/or hearing impairment.
• History of encephalitis, ictus or seizures excluding feverish convulsions during childhood.
• Severe cerebral macrovascular (i.e., multi-stroke) disease or brain tumor (metastasis/brain cancer) as verified by magnetic resonance imaging (MRI).
• Any contraindication to MRI acquisition, (i.e., metal implants) or phobia to performing the scan as determined by the onsite physician.
• Previous participation in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening and/or administration of a radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study.

A total of 440 participants enrolled in the ALFA project (STUDY 45-65 FPM/2012) will be selected and physiologically characterized with 18F-Flutemetamol and 18F-FDG PET scans.