Table 1 Exclusion criteria

✗ Dementia secondary to disorders other than Alzheimer’s disease dementia.

✗ Any central nervous system disease other than AD that, according to the investigator, could be associated with worsening cognition. Patients with epileptic seizures in the last 2 years had to be excluded.

✗ A disease or condition which in the opinion of the investigator was likely to interfere with trial testing procedures or put the patient at risk when participating in this trial.

✗ Any documented active or suspected malignancy or history of malignancy with the need of concomitant treatment that interfered with the investigational product.

✗ Patients with a life expectancy of less than 2 years were also excluded.

✗ Any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.

✗ Severe renal impairment defined as a GFR < 30 mL/min/1.73 m² at screening.

✗ Hemoglobin less than 120 g/L (12 g/dL) in men or 115 g/L (11.5 g/dL) in women in the screening lab report. History of hemoglobinopathy such as thalassemia major or sickle cell anemia.

✗ Clinically significant uncompensated hearing loss in the judgment of the investigator (use of hearing aids was allowed).

✗ Any suicidal behavior in the past 2 years (i.e., actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).

✗ Any suicidal ideation of type 4 or 5 in the C-SSRS in the past 3 months (i.e., active suicidal thought with intent but without a specific plan or active suicidal thought with plan and intent).

✗ Known history of HIV infection.

✗ Significant history of drug dependence or abuse (including alcohol, as defined in the DSM-V or in the opinion of the investigator) within the last 2 years.

✗ Previous participation in investigational drug studies of dementia of Alzheimer’s type within 3 months prior to screening. Patients having received any active treatment in studies targeting disease modification of AD were excluded. Previous participation in studies with non-prescription medications, vitamins, other nutritional formulations, or non-pharmacological treatments was allowed.

✗ Treatment with restricted medication prior to visit 1 and/or during the screening period.

✗ Planned elective surgery requiring general anesthesia or hospitalization for more than 1 day (requiring an overnight stay) during the study period.

✗ Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3× upper limit of normal as determined during screening.