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

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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