Senolytic Therapy to Modulate Progression of Alzheimer's Disease

Up to 40 potential candidates will be pre-screened to identify eligible men and women ages 65 years and over with a clinical diagnosis of early AD on a stable dose of cholinesterase inhibitors for at least 3 months (for example, Aricept).

Eligible participants will undergo laboratory assessments of blood and urine, receive study medications over a twelve week period, and complete pre- and post-treatment testing including: an MRI for digital imaging of the brain; lumbar puncture to obtain cerebrospinal fluid; memory and thinking assessments; quality of life questionnaires; and tests of walking, balance and strength, all of which will be done for research purposes only.

Participants must be accompanied by a Legally Authorized Representative and have no travel plans for 4-5 months that would interfere with study visits.

Inclusion criteria

• Age 65 years or above.
• Clinical diagnosis of AD (MoCA 10-20 and Clinical Dementia Rating Scale/CDR = 1) on a stable dose of cholinesterase inhibitors for at least three months
• Body Mass Index (BMI) within range of 19 - 35 kg/ m2
• Labs: Normal blood cell counts without clinically significant excursions (WBCs: 4,500-10,500 cells/mcL; absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 140-450 K/uL; hemoglobin 12.0-17.5 grams/dL); liver and renal function (AST 10-40 IU/L, total bilirubin 0.1-1.4 mg/dl); cholesterol (<240 mg/dl), triglycerides (<300 mg/dl), and glucose control (HbA1c < 7%). PT/PTT/INR within normal limits
• Participants must be accompanied by a Legally Authorized Representative designated to sign informed consent and to provide study partner reported outcomes at all remaining visits
• Participants must have no plans to travel over the next 4-5 months that interfere with study visits following consent

Exclusion criteria

• Hearing, vision, or motor deficits despite corrective devices;
• Alcohol or drug abuse;
• MRI contraindications;
• Myocardial infarction, angina, stroke or transient ischemic attack in the past 6 months; QT interval >440 on ECG will not be enrolled. Chronic heart failure will be exclusionary;
• Participants with coagulation disorders;
• Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments;
• Uncontrolled diabetes (HbA1c > 7% or the current use of insulin);
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
• Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication;
• Current use of quinolone antibiotics.
• Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg).
• Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease.
• History of or MRI-positive for any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture