A Multicenter national prospective cohort study including at least 2300 individuals consecutively recruited from French Research Memory Centers and followed-up over 5 years.

The increasing incidence of Alzheimer's disease (AD) and related disorders with the change in the world age demographic is a source of major public health concern. Early and accurate identification of individuals at high risk of Alzheimer's Disease has become a priority. Over the last years, research has focused on the concept of "Mild Cognitive Impairment" which happens to be a heterogeneous condition as, depending on the studies, Mild Cognitive Impairment patients' conversion rates to dementia range from 2 to 15 percent per year. A study of the full range of stages of evolution, from preclinical stage, to clinical expression of dementia or death is therefore of utmost importance to improve our knowledge on AD and trigger the development of new treatments, especially if between stages transition can be related to neuroimaging (either structural or molecular), biological (Cerebro-Spinal Fluid, serum or plasma) or vascular damages markers. However, if all the above markers have been shown to be individually associated with worsening of cognitive status, no prior study has simultaneously explored the association of a large panel of risk factors and biomarkers with the progression through early signs of cognitive impairment until AD in a large sample of study participants. In parallel to improving the knowledge on AD, it is also important to better estimate the social and economic burden of AD and their consequences on the individuals and their circle and how they evolve from early phase (pre-clinical) of the disease to the most severe stages.

This cohort, solution to the item 29 of the Plan Alzheimer 2008-2012, has been developed according to the initial memorandum of understanding prepared by the "Comité Plan Cohortes" of the Fondation Plan Alzheimer, and taking on board comments provided by the Scientific Advisory Board (July 2010) of the Fondation Plan Alzheimer and the whole working groups constituted for the preparation of the pilot phase: clinicians, neuro-imaging specialists, biologists, social sciences researchers (from June 2010). The cohort is built to fulfil the guiding principles as follows:

• It should be scientifically original and identify hypothesis-driven research, allowing a corpus of new or confirmatory knowledge of a high-level of evidence to be acquired. In addition, the infrastructure (standardised collection of socio-demographic, clinical, imaging, biological data) may allow to respond, in a timely manner, to additional questions that may emerge over time;
• An interdisciplinary approach is set up as the condition of individuals affected by neurodegenerative dementias involves clinical and biological aspects but also environmental, social and economic components;
• While pursuing its own original scientific objectives, the cohort should have the potential for a comparison with other equivalent cohorts around the world.

This cohort will be including individuals at high risk of developing a neurodegenerative dementia. As such, the cohort is aiming at providing results with an expected impact for those individuals of the same profile, as well as their caregivers and their case management.

One expected impact is to increase knowledge on the progression from early signs of cognitive impairment to AD and estimate associations between these signs and level of biomarkers assessed through imaging or blood or CSF samples. Another major expected impact is to standardise and harmonise protocols in terms of clinical and neuro-psychological examinations, biological markers, neuroimaging markers, diagnosis of dementia, support to caregivers and informants.

Inclusion Criteria:

• Aged 18 years and above
• Having at least a light cognitive deficit defined as performing worse than one standard deviation to the mean (compared to age and educational norms) in one or more cognitive domains (assessed from a neuropsychological tests battery exploring memory, language, praxis, vision, executive functions); this deviation being identified for the first time by tests performed less than 6 months preceding date of inclusion
• Or having isolated cognitive complaint regardless of its duration while being 60 years and older
• Clinical Dementia Rating scale <=0.5 and not demented
• Visual and auditory acuity adequate for neuropsychological testing
• Having signed an informed consent
• Being affiliated to health insurance

Exclusion Criteria:

• Being under guardianship
• Residence in skilled nursing facility
• Pregnant or breast feeding women
• Alzheimer's disease caused by gene mutations
• Meeting brain MRI exclusion criteria (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body) or refusing MRI
• Having a neurological disease such as: treated epilepsy, treated Parkinson's disease, Huntington disease, brain tumour, subdural haematoma, progressive supranuclear palsy, history of head trauma followed by persistent neurological deficits
• Stroke that has occurred in the last three months
• Schizophrenia history (DSM-IV criteria)
• Illiteracy, is unable to count or to read

Outpatients from French Research Memory Centers with at least a light cognitive deficit defined as performing worse than one standard deviation to the mean in one or more cognitive domains or an isolated cognitive complaint regardless of its duration while being 60 years and older.