Safety and Feasibility of Dasatinib and Quercetin in Adults at Risk for Alzheimer's Disease

Senolytics To Alleviate Mobility Issues and Neurological Impairment in Aging

The purpose of this pilot study is to demonstrate the safety and feasibility of administering intermittent doses of Dasatinib and Quercetin (D+Q) in older adults at risk of Alzheimer's disease (AD). The study will evaluate whether giving D+Q may improve cerebral blood flow regulation, mobility, and cognition in older adults, and thus may prevent progression to Alzheimer's disease.

The investigators will conduct a 12-week single arm, open label, pre-post pilot study in 12 adults aged 65 or older with slow gait speed (<1.0 m/sec) and Mild Cognitive Impairment (MCI, defined as a Telephone Montreal Cognitive Assessment Score (MoCA) <19). Participants will be asked to take 100mg of Dasatinib and 1,250mg of Quercetin for 2 consecutive days, every two weeks over a period of 12 weeks (12 doses in total, given over 6 cycles).

At baseline, enrolled participants will undergo gait speed and neurocognitive testing, and provide blood and urine to evaluate biomarkers of senescence. At visits 3,4, 6, and 7, participants will have safety labs drawn, and the study team will assess medication adherence and adverse events. At visits 2, 5, and 8, participants will undergo cognitive assessments, gait speed testing, cerebral blood flow and neurovascular coupling testing. At the final study visit, participants will again provide blood and urine to assess biomarkers of senescence.

Inclusion Criteria:

• Men and women >/= 65 years
• Ambulatory,
• Community dwelling,
• Slow gait speed (<1 m/second),
• Mild Cognitive Impairment (Telephone MoCA score <21, which is indicative of cognitive impairment)

Exclusion Criteria, or as per clinical judgment:

• Telephone MoCA score <10 points
• Unwilling to take study medications or follow study protocol
• Inability to independently perform Katz Activities of Daily Living (ADLs),
• Allergies to Dasatinib or Quercetin,
• Hospitalization within 6 months,
• Unstable coronary artery disease (myocardial infarction within 6 months or angina),
• Stroke or transient ischemic attack in the past 6 months,
• Chronic heart failure,
• Current or chronic history of liver disease,
• Neurodegenerative disease including Parkinson's disease,
• Anemia,
• Chronic renal disease,
• Drug or alcohol abuse in the last 5 years,
• QTc prolongation,
• Thrombocytopenia,
• Neutropenia,
• Prolonged prothrombin time or INR,
• Indications of current fluid retention,
• History or current diagnosis of pulmonary hypertension,
• Inability to insonate the middle cerebral artery through a temporal bone window on at least one side using transcranial Doppler ultrasound, or
• Chronic use of any of the following medications: anti-arrhythmic medications, antipsychotics, anxiolytics, anti-platelet or anti-coagulant medications other than aspirin, quinolone antibiotics, or drugs metabolized by the same liver enzymes as Quercetin or Dasatinib.