Evaluate efficacy and safety of Cerezen (Renew™ NCP-5) in improving cognitive function in subjects with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD) with comorbid type 2 diabetes (T2D).

Vascular impairment associated with T2D doubles the incidence of MCI and dementia. Cerebral hypoperfusion and endothelial dysfunction are found in AD and T2D. Physical activity improves cerebral vascular flow and lowers risk of dementia in comorbid T2D. Cerezen is external counterpulsation therapy used for refractory angina and heart failure that has received FDA Breakthrough Designation based on a successful pivotal trial in MCI and mild AD. Like physical activity, Cerezen increases cardiac output, shear stress, angiogenesis/arteriogenesis, and improves endothelial function.

Randomized, single-blind, sham-controlled pivotal trial with 10 US sites. Subjects 55-85 years, with clinical diagnosis of dementia due to AD or MCI due to AD, and a Montreal Cognitive Assessment score ≥11 were given Cerezen (n=95) or active sham (n=95), stratified by disease severity and CV risk score. Primary endpoint was mean change from baseline in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-Cog) at 12, 18, and 24 weeks, powered for a 2-point delta.

Primary endpoint was met in the total population (delta, -4.45 points; p<0.012). Subgroup analysis of subjects with T2D (n=36) showed the Cerezen group improved in cognition from baseline as measured by VADAS-Cog (delta, -21.04 points; p<0.0002). Every subject with T2D improved in the Cerezen group vs mixed results in the sham group at 24 weeks. Cerezen significantly improved ADLs in this population (delta, 11.22 points; p=0.0045) at 24 weeks. Trend-level improvement in pulse pressure was seen with Cerezen vs sham in this group. Cerezen was safe and well tolerated.

Cerezen improved cognitive performance, possibly mediated by improved endothelial function and cerebral perfusion, in the T2D population with MCI or mild AD dementia.