Investigating Brain Insulin Resistance in Alzheimer Disease with IntraNasal Insulin : a Multimodal Neuroimaging Study

Prior treatment

• Current recreational drug or alcohol abuse.
• Being under corticosteroid treatment (non-topical treatment)
• Taking a hormonal therapy (e.g., post menopausal, oncological treatment…)
• Type 1 DM or Type 2 DM treated with insulin.

Other illness

• Any acute medical condition that required either hospitalization or surgery within the past 6 months.
• Current or past psychiatric illness (according to the Mini International Neuropsychiatric Interview [MINI])
• For healthy participants (groups 1 and 3), having a first degree relative with dementia onset before 65 years (Alzheimer, Lewy body disease, Parkinson)
• Dementia (Mini-Mental State Examination [MMSE] scores ≤ 20) for group 2 and 3.
• Serious systemic disease that would interfere with the conduction of the trial .
• Based on selection of Dementia from neurologic causes, Hachinski Ischemia Score > 4 (55).
• The subject has an allergy to the IMP.
• History of bleeding disorder.
• History of severe hypoglycaemia.
• Current Ears Nose Throat (ENT) infection.

Other

• Dense or tight hair braiding or scalp lesions, preventing adequate EEG cap positioning.
• Pregnancy and/or breastfeeding.
• Claustrophobia.
• Metallic component (e.g. pacemaker) incompatible with the MRI acquisition.
• Participants over 120 kg for radioprotection issues.
• The subject has participated in a clinical trial investigation within 1 month of this study.
• CDR score ≥2, witch will be evaluated before inclusion by investigator for group 2 and 3.
• Being under birth-control pill containing ethinyl estradiol.
• The use of anticoagulants warfarin (Coumadin) or dabigatran (Pradaxa)
• Participant being under any chronic Intranasal treatment.
  • Criteria susceptible to postpone study inclusion:
• Clogged or runny nose.
• Fever during the last 24 hours.
• Consumption of caffeine during the last 24 hours.
• Fasting period inferior to 12h before study visits.
• Sleep deficiency the night preceding study days as assessed by Pittsburgh Survey

• For the young subject group (group 1):
• Men and women aged 21-45 years old.
• Women under effective contraception.
• For Women, the study protocol should be performed during the follicular phase of the menstrual cycle, because of …
• Subjects must be proficient in speaking, reading and understanding French in order to be assessed with the neuropsychological tests battery.
  • For the MCI/AD group (group 2):
• Men and women aged 40-85 years old.
• Patients included on the registry of Neurodegeresence study in Hopital Erasme.
• Patients are capable of providing informed consent.
• Patients are proficient in speaking, reading and understanding French, in order to be assessed with the neuropsychological tests battery.
• Being diagnosed with amnestic MCI or probable mild AD, according to the core clinical criteria of the NIA and Alzheimer's Association guidelines.
• If the patient has a prescription medication acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) and/or memantine doses has to be stable since 1 month at least.
  • For the group 2 - matched controls (group 3):
• Men and women aged 40-85 years old.
• Participants capable of providing informed consent
• Subjects are proficient in speaking, reading and understanding French, in order to be assessed with the neuropsychological tests battery.