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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
15
Hebrew Senior Life
Boston, Massachusetts, United States
Neurovascular Coupling
Change in cerebral blood flow during an N-back cognitive task using transcranial doppler ultrasound.
Time frame: Screening, 8, and 14 weeks
Executive Function
Assess change in executive cognitive function using TRAILS test, corrected for response time. Higher scores indicate worse executive functioning.
Time frame: Baseline, 8, and 14 weeks
Gait Speed
Assess change in gait speed. Performed without a distracting cognitive task.
Time frame: Baseline, 8, and 14 weeks
Montreal Cognitive Assessment (MoCA) Score
The Montreal Cognitive Assessment evaluates global cognition. Scores range from 0-30 points, with higher scores indicating better cognition
Time frame: Baseline, 8, and 14 weeks
Physical Performance
Assessment of overall physical function using the short physical performance battery (SPPB) scored from 0-12, based on a composite of balance, strength, and walking speed. Higher scores indicate better mobility.
Time frame: Baseline, 8, and 14 weeks
Mobility
Test of mobility using timed up and go test, including standing from a chair, walking, and turning.
Time frame: Baseline, 8, and 14 weeks
Grip Strength
Measure of grip strength using a hand dynamometer.
Time frame: Baseline, 8, and 14 weeks
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Gait Speed During Cognitive Task
Measure of gait speed during a cognitive task.
Time frame: Baseline, 8, and 14 weeks
P16 ink4a Expression in CD3 Positive Cells
Measure of P16 ink4a expression in senescent CD3 lymphocytes in the blood.
Time frame: Screening and 14 weeks
SASP Factors in Blood and Urine
Measure of the senescence-associated biomarkers IL-1alpha picogram/mL and IL-6 picogram/mL.
Time frame: Screening and 14 weeks
SASP Factors in Blood and Urine
Measure of the senescence-associated biomarkers MMP-9 nanograms/mL and MMP-12 nanograms/mL.
Time frame: Screening and 14 weeks