Prodromal Alzheimer's Disease Treatment Trial

The LipiDiDiet study was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial done in 11 study sites in Finland, Germany, the Netherlands, and Sweden (appendix) with one to four optional, 12-month, double-blind extension periods. Participants were primarily recruited from memory clinics and had routine assessments in the year before screening. The study was completed as planned. Here we report 24-month findings; extension studies are currently ongoing and will be reported later. We enrolled participants aged 55–85 years with a Mini-Mental State Examination (MMSE) score of 24 points or higher (≥20 if education level ≤6 years) who fulfilled criteria for prodromal Alzheimer's disease³ (link) as defined by episodic memory disorder (performance below one standard deviation on two of eight cognitive tests [at least one on memory]) and evidence for underlying Alzheimer's disease pathology based on positive findings from at least one of the following diagnostic tests: CSF, MRI, and ¹⁸F fluorodeoxyglucose (¹⁸F-FDG) PET analysis (full list of inclusion criteria is in the appendix). We excluded participants with dementia according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV); historical use of donepezil, rivastigmine, galantamine, or memantine, use of omega-3 preparations, alcohol or drug abuse, major depressive disorders (DSM-IV) or other concomitant serious conditions, intake of vitamins B6, B12, folic acid, vitamin C, or vitamin E of more than 200% of the recommended daily intake, those who participated in any other clinical trial in the last 30 days, and with an MRI or CT scan consistent with a diagnosis of stroke, intracranial bleeding, mass lesion, or normal pressure hydrocephalus (minimal white matter changes and up to two lacunar infarcts judged to be clinically insignificant were allowed). Participants who progressed to dementia during the trial could remain in the trial and start approved Alzheimer's disease medication, according to the clinician's judgment. The protocol was amended to allow participants who progressed to dementia to switch to the active product after it became generally available (appendix). The study protocol and consent forms were approved by the local ethical committees of all participating sites, and all participants provided written informed consent before study participation. The study was done in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines.