Effect of CAFfeine on Cognition in Alzheimer's Disease

Sporadic Alzheimer's disease is a multifactorial illness arising a major medico-economic stakes for our aging societies. There is currently no curative treatment available. Coffee is a complex beverage with psychostimulant properties whose main effective element, caffeine, has a pleiotropic effect on the central nervous system. Caffeine pharmacological properties enable its use like an Alzheimer's disease symptomatic treatment. Its supposed benefits mustn't obscure anxiety and insomnia caffeine effect at large dose, which Alzheimer's patients might be more vulnerable. The main study objective is to evaluate placebo-controlled caffeine efficacy (30 treatments weeks) on cognitive decline in Alzheimer's disease dementia at beginning to moderate stage (MMSE 16-24).

Inclusion Criteria: * Age ≥ 50 at screening * Probable Alzheimer dementia according to the criteria of the National Institute on Aging-Alzheimer's Association; diagnosis must be supported by brain imaging (CT or MRI) and blood test (including ionogram, kidney and liver function, calcemia, CRP, TSH, B12 vitamins and folates) performed in routine care * MMSE score ≥16 * Presence of an informant and caregiver, living with the patient * IAChE and/or Memantine treatment non-compulsory ; If implemented it must be effective and stable for 2 months before the selection visit and must remain stable for the duration of the study Exclusion Criteria: * Patients who refuse to adopt a low caffeine diet (eviction of tea, caffeinated sodas, chocolate in large quantities) * Current major depressive episode according to DSM-5 criteria * Another chronic pathology of the central nervous system * Major anxiety according to the clinician (consistent with the corresponding nPI-R items that must indicate a severity \>2 and an impact \>3) * Sleep disorders defined by severity and an impact on NPI-R; a patient fitted for OSA may be included if the device has been in use for 3 months and well tolerated (stable) * Decompensated heart disease or severe rhythm disorder (excluding slow, treated and stable chronic atrial fibrillation) * Active smoking * For childbearing women : pregnancy in progress or planned (A pregnancy test will be performed) * Patients who take forbidden treatment : * Psychotropic treatments introduced or modified \< 2 months before inclusion * Chronic use of CYP1A2 inducing or inhibiting drugs * All caffeine-containing specialties * Drugs that influence caffeine metabolism * Drugs that may interact with caffeine