Patient case (clinical description): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient's own account: I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Clinical trial: ADDIA Chronobiological Study

Eligibility criteria:
Inclusion Criteria for Alzheimer patient group:

          -  Signed Informed Consent.

          -  Male or female subject, between 55 and 85 years inclusive.

          -  Specific clinical phenotype of AD: Presence of an early and significant episodic
             memory impairment (isolated or associated with other cognitive or behavioural changes
             that are suggestive of a dementia syndrome) that includes the following:

               -  Gradual and progressive change in memory function reported by patient or
                  informant over more than 6 months.

               -  Objective evidence of an amnesic syndrome of hippocampal type, based on
                  significantly impaired performance on an episodic memory test with established
                  specificity for mild to moderate AD.

          -  Cognitive tests including MMSE score 12 ≤ MMSE ≤ 25 for mild to moderate AD (measured
             in the last 3 months), b) Scores of other tests routinely practiced at the hospital
             for measurement of memory and cognition shall be compatible with mild to moderate AD.

          -  Neuroimaging compatible with a diagnosis of mild to moderate AD.

          -  Cerebrospinal fluid (CSF) biomarkers showing at least 2 positive levels out of the 3
             biomarkers: CSF Aβ1-42 and tau (Phosphorylated-Tau and/or Total-Tau). CSF collection
             and data being only retrospective.

        Inclusion Criteria for healthy controls:

          -  Signed Informed Consent.

          -  Male or female subject, between 55 and 85 years inclusive.

          -  Normal clinical and cognitive scores as measured using standard neuropsychological
             tests.

          -  Normal scores in other neuropsychological tests routinely practiced at the hospital
             for measurement of memory and cognition.

          -  No abnormal neuroimaging findings in at least structural MRI.

        Exclusion Criteria:

          -  Any subject who did not sign the informed consent form.

          -  Any chronic neurodegenerative disease (vascular dementia, Parkinson's disease,
             Creutzfeldt Jacob, Huntington's disease, etc.), acute neurodegenerative disease
             (stroke), history or presence of clinically relevant psychiatric history
             (schizophrenia, psychosis), some chronic inflammatory diseases that impact blood cells
             (e.g. anemia of inflammation and chronic disease) and some cancers (that impact blood
             cells: e.g. leukemia), major sensory deficits that could interfere with cognitive
             assessment (visual and auditory), epilepsy.

          -  Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice
             a month).

          -  Blood donation, any volume, within 2 months before inclusion.

          -  Neutropenia (Neutrophils < 1500/mm3).

          -  Thrombocytopenia (platelets: < 100,000/mm3, rule out EDTA-induced
             pseudothrombocytopenia).
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 55 Years old.
Subject must be at most 85 Years

Eligibility (NLI label): Entailment