RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β

Retinal amyloid-β is identified using optical coherence tomography (OCT)-autofluorescence imaging and measured using a composite score called the retinal amyloid index (RAI), a continuous variable incorporating number, total area, and total fluorescence intensity of retinal Aβ spots. The change in RAI scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures.

The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is used to differentiate stages of cognitive impairment. It assesses six cognitive and functional domains including memory, orientation, judgement, community affairs, home hobbies, and personal care. Each of the six CDR domains is scored 0 to 3, with the Sum of Boxes (SB) being the sum of the six domains on a 0-18 numerical scale. The CDR-SB is scored by trained physicians after interviewing both participants and their informants. Change in CDR-SB scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures.

The Mini Mental State Examination (MMSE) is an instrument used to screen for cognitive impairment. The test consists of 11-questions that evaluate five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The MMSE is scored on a numerical 0-30 scale by trained physicians after interviewing participants. Change in MMSE scores will be compared between RQC and control groups using linear mixed-effects models for repeated measures.

Superactivated platelets (SAPs) are a procoagulant sub-type of activated platelet that are increased in mild cognitive impairment (MCI) and Alzheimer's disease and are associated with disease progression [Pfahler, 2018; Prodan, 2011]. SAPs are prepared from whole blood samples and induced in vitro by dual platelet agonists thrombin and convulxin (collagen substitute). SAPs are identified by inactivated integrin αIIbβ3 and high levels of surface fibrinogen binding and measured using flow cytometry as the percentage of total platelets positive for SAP markers. Change in the percentage of SAPs will be compared between RQC and control groups using linear mixed-effects models for repeated measures.

The Pearson correlation coefficient (r) between change in retinal amyloid-β as measured using the retinal amyloid index (RAI) score and change in CDR-SB scores as measured using the 0-18 numerical scale equating to the sum of the six CDR domains, each of which is scored 0 to 3. The retinal amyloid-β RAI score is a continuous variable that incorporates number, total area, and total fluorescence intensity of retinal Aβ spots. For example, a subject may have a RAI score of 20.4 and a CDR-SB score of 1.

The Pearson correlation coefficient (r) between change in retinal amyloid-β as measured using the retinal amyloid index (RAI) score and change in MMSE scores as measured using the 0-30 numerical MMSE scale. The retinal amyloid-β RAI score is a continuous variable that incorporates number, total area, and total fluorescence intensity of retinal Aβ spots. For example, a subject may have a RAI score of 20.4 and a MMSE score of 26.

The effect of RQC on clinically significant cognitive decline (defined as a decrease of 4 or more points from baseline on MMSE) will be evaluated using Cox proportional hazards models.

The effect of RQC on clinically significant cognitive decline (defined as an increase of 0.5 or more points from baseline on CDR-SB) will be evaluated using Cox proportional hazards models.

Adverse events (AEs) and serious adverse events (SAEs) will be identified and graded according to the CTCAE v5.0 after interviewing participants and reviewing study records.