Dosage and Efficacy of Probucol-induced apoE to Negate Cognitive Deterioration

- Family history of one or more parents or multiple siblings who developed Alzheimer-like dementia, as established by review of history and/or medical records, and by responses to a brief questionnaire describing characteristics of the relatives' condition

- Aged 60+. May be aged 55-59 only if at least one parent or sibling experienced onset of Alzheimer's dementia at an age no more than 15 years beyond the prospective participant's current age

- At least six years of formal education

- Sufficient fluency in spoken and written English and/or French to participate in study visits and in psychometric testing

- A collateral respondent available to provide information on the cognitive and health status of the participant, and to assist with monitoring of study interventions, if needed

- Willingness to undergo four lumbar punctures for collection of CSF

- Affirmation of prior informed consent to undergo genetic testing for APOE and other known or suspected AD risk factors

- Ability and intention to participate in study visits per protocol, in the opinion of a study physician

- Willingness to limit use of over-the-counter or prescription medicines (e.g., tricyclic antidepressants, anti-histamines) known to prolong QTc interval, or to potentiate the tendency of probucol to prolong this interval, in the opinion of a study physician

- If on a statin or other lipid lowering drug that, in the opinion of a study physician, can safely be co-administered with probucol, willingness to remain on a stable dose of this medication during the entire trial period.

- Provision of informed consent for this trial.

- Known or identified cognitive disorder diagnosed previously by a physician, psychologist, nurse-clinician, or other health care provider, or by StoP-AD staff

- Past or present use of a commercially available acetyl-cholinesterase inhibitor including tacrine, donepezil, rivastigmine, or galantamine

- Past or present use of memantine or other approved cognitive enhancement prescription agent

- History of heart disease, myocardial infarction or documented acute coronary syndrome, or arrhythmia (including atrial fibrillation)

- Corrected QT interval using Bazett's formula (QTcB) interval > 450 msec for males or 470 msec for females as detected by EKG and confirmed by consultant cardiologist

- Clinically significant hypertension, anemia, liver disease, or kidney disease, in opinion of a study physician (participants with treated hypertension who are normotensive as a result of intervention may be enrolled.)

- Concurrent use of over-the-counter or prescription medicines (e.g., tricyclic antidepressants, anti-histamines) known to prolong QTc interval, or to potentiate the tendency of probucol to prolong this interval, in the opinion of a study physician

- Any inflammatory or chronic pain condition that necessitates regular use of opiates (e.g., oxycodone, hydrocodone, tramadol, meperidine, hydromorphone), or NSAIDs (more than 4 doses / week)

- Current plasma creatinine > 132 mmol/l (1.5 mg/dl)

- Current alcohol, barbiturate or benzodiazepine abuse or dependence (in opinion of study physician)

- Any other medical condition that, in the opinion of a study physician, makes it inadvisable for the participant to be assigned to regular dosage of probucol

- Enrolment in any trial or experimental protocol that, in the opinion of a study physician, is likely to interfere with PREVENT-AD or any of its derivative protocols including this one

- Any other condition that, in the opinion of a study physician, makes it medically inappropriate for the participant to enroll in the program