Safety of a Strategy Combining Etanercept Administration With Repeated Contrast Ultrasound in Patients With Alzheimer's Disease

Inclusion criteria

• Positive diagnosis of Alzheimer's disease according to IWG2 criteria
• Biological profile in favour of Alzheimer's disease
• Age ≥ 50 years and ≤ 85 years
• Affiliated or beneficiary of a social insurance scheme
• Patient suffering from mild AD with little or no impact on autonomy, MMSE score ≥20 at inclusion
• Fazekas score <=1
• Presence of a family or a person at home who can monitor the occurrence of adverse events
• Sufficient command of the French language to take neuropsychological tests.
• Have undergone a full neuropsychological assessment within 6 months.
• If anticholinesterase treatment, stability of treatment for at least three months.
• Signed, free and informed consent from the patient and the trusted support person.

Exclusion criteria

• Patient previously treated with anti-TNF alpha (e.g. etanercept).
• Other cause of major neurocognitive disorder.
• Participation in another drug study
• Absolute contraindication to MRI (e.g. pacemaker, implantable stimulator, intra-orbital metallic foreign body);
• Contraindication to lumbar puncture.
• History of bleeding diathesis;
• Severe chronic respiratory disease;
• Patient on anticoagulant therapy
• Right-to-left shunt, severe pulmonary arterial hypertension;
• Known cerebral vasculopathy; (Fazekas greater than 1), sequelae of ACI.
• Treatment with Anakinra, abatacept or sulfasalazine.
• Patients who have undergone major surgery within 28 days of the first day of the study.
• Allergy to gadolinium, or any contraindication to contrast products used for brain imaging (in particular severe renal insufficiency with a glomerular filtration rate <30 ml / min / 1.73 m2).
• Allergy to xylocaine
• Epilepsy or drugs that lower the epileptogenic threshold (see Appendix 6).
• Major depressive syndrome despite appropriate treatment and/or psychotic symptoms (according to DSM IV);
• MRI characteristic of an active or acute neurological process (infection, tumour) or macro-haemorrhage.
• Non-menopausal women
• Patient benefiting from a legal protection measure other than guardianship or curatorship.
• Optic neuritis
• Manifestations of multiple sclerosis
• Live vaccinations (yellow fever, BCG) within 4 weeks of starting etanercept treatment.
• History of hepatitis B or C
• Patients with recent acute coronary syndrome or unstable ischaemic heart disease.
• History of recurrent or chronic infections, or a predisposing condition such as severe or poorly controlled diabetes.
• Patients who have undergone major surgery within 28 days of the first day of the study.

Contraindications related to etanercept :

• Hypersensitivity to etanercept or to any of the excipients of Benepali
• Sepsis or risk of sepsis
• Active infection including chronic or localised infections.

Contraindications associated with SonoVue (ultrasound contrast medium)

• Hypersensitivity to Sonovue.
• Right-to-left shunt
• Severe PAH (pulmonary arterial pressure greater than 90 mmHg)
• Uncontrolled hypertension
• Respiratory distress syndrome
• Conditions suggesting cardiovascular instability for which dobutamine is contraindicated