Evaluating the relationship between vascular endothelial growth factor (VEGF) and cognitive improvements following exercised‐primed transcranial direct current stimulation (tDCS) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD)

Abstract

AbstractBackgroundVEGF has been associated with memory decline in neurodegenerative diseases. As an angiogenesis biomarker, VEGF should be analyzed to better understand the variable treatment response from tDCS, a non‐invasive brain stimulation, and the priming effect of exercise on tDCS for memory improvements in MCI and AD. Using blinded data from an ongoing clinical trial (EXPRESS), we aimed to evaluate the ability of serum VEGF to predict improvements for recall memory in MCI and mild AD patients.MethodParticipants were enrolled in a five‐week, randomized, blinded tDCS clinical trial to receive either exercise and sham tDCS, exercise and tDCS, or exercise‐education only and tDCS intervention. Exercise groups included a three‐week ramp‐up period. Participants were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria for major or mild neurocognitive disorder due to AD or mixed AD/vascular disease (etiology). VEGF serum concentrations were measured from blood samples at screening. Recall memory was assessed using the Word Recall Task from the Alzheimer's Disease Assessment Scale‐Cog (ADAS‐Cog) at screening, baseline and endpoint (2 weeks from baseline). Analysis of variance (ANOVA) evaluated recall memory and VEGF concentrations at screening between the two etiology groups. Multiple linear regression analysis determined the association between VEGF concentrations (pg/mL) and recall memory score improvements over treatment period (Δrecall).ResultIn 17 participants (58.8% male, 70.6% MCI, mean(±SD) age 72.8±7.2, years of education 17.1±2.0, VEGF 332.4±157.5, Δrecall 0.5±0.9), six participants (35.3%) were diagnosed as AD etiology only and eleven participants (64.7%) were mixed vascular/AD etiology with no differences in recall memory [F(1,15)=0.019,p=0.893] or VEGF concentrations [F(1,15)=1.488,p=0.241] between these two groups at screening. The regression analysis found that VEGF and etiology predicted Δrecall [F(2,14)=7.103,p=0.007,R2=0.504]. Controlling for etiology, VEGF concentrations were associated with Δrecall [B(SE)=‐0.003(0.001),p=0.039]; Δrecall decreased 0.003 for each pg/mL of VEGF.ConclusionIn this pilot sample, lower serum VEGF concentrations at screening predicted greater recall memory improvements when controlling for etiology. After un‐blinding, longitudinal analysis and a larger sample size will allow further examination of VEGF’s predictive and monitoring capacity as a biomarker for recall memory and other cognitive responses to exercise‐primed tDCS.