Before Alzheimer's disease (AD) clinical symptoms appear, there is a long period when changes in the brain occur. In this long asymptomatic period or preclinical phase, studies with populations at risk of developing AD have shown cognitive differences compared to control groups without such risk. There is a need for short, sensitive, easily administered, reproducible, non-expensive and independent of socio-demographic influences tests enabling the detection of pre-symptomatic variations in memory, when the memory decline is still within a normal range.

Study main hypothesis: When evaluated with high-demanding tests of memory and executive function, the cognitive performance of cognitive healthy people aged between 45 and 65 and, extensively, to a group of up to 75 years, will vary significantly depending on clinical, socio-demographic and genetic features

The purpose of Study 45-65 is to assess if:

• Endogenous factors (clinical history, risk factors, genetic factors APOE4, etc…), exogenous (socio-demographic, ambient and lifestyle variables) and cognitive reserve (including bilingualism) influence cognitive performance.
• New and/or updated tests translated and validated in Spanish and Catalan when needed, will provide accurate and sensitive measurements of the variability of cognitive performance in this target population, representative of the preclinical phase of Alzheimer's disease.

An optional visit is offered to study participants that includes: cerebral magnetic resonance, vascular ultrasound and olfactory testing.

Inclusion Criteria:

1. Men and women, aged between 45 and 75 years

2. Spanish and/or Catalan speakers

3. Agreement with the study procedures and tests:

   1. Clinical Interview and questionnaires associated to risk factors
   2. Cognitive tests
   3. Blood sample extraction for DNA analysis

4. Close relative involvement for functional evaluation of the volunteer

5. Signature of informed consent

Exclusion Criteria:

1. Cognitive impairment: MMSE <26, o MIS <6, or orientation subtest of the Barcelona Test II <68, o category fluency (animals) <12
2. Functional status impairment: CDR > 0
3. Severe auditory and/or visual impairment
4. Neurodevelopmental and/or psychomotor disorder
5. Significant diseases that could currently interfere with cognition: renal failure on hemodialysis, liver cirrhosis, chronic lung disease with oxygen therapy, solid organ transplantation, fibromyalgia, active cancer in treatment or any other disease the investigator considers could affect the participant cognition
6. Major psychiatric disorders (DSM-IV-TR) or diseases that could affect cognitive abilities: major depression, bipolar disorder, schizophrenia and dementia.
7. Neurological disorders: Parkinson's disease, stroke, epilepsy and treatment with frequent seizures (> 1/month) in the past year, multiple sclerosis or other serious neurological disease.
8. Brain injury interfering with cognition: history of head trauma with parenchymal lesion or extraaxial macroscopic large vessel ischemic stroke or hemorrhagic stroke, brain surgery, brain tumors and other causes that can generate acquired brain damage (cerebral chemotherapy or radiotherapy)
9. Family history of Alzheimer's disease with autosomal dominant (3 affected in two different generations) and early onset age (<60 years).

Cognitive normal men and woman aged 45-75 years