A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline

Abstract

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.

Figure.

The effect of statin-exercise therapy on cognition in CAD patients with mild cognitive decline. (A) Box-and-whisker plot showing the effect of combined exercise and statin treatment for 5 months on the cognitive function using the MMSE test. (B) Box-and-whisker plot showing the effect of statin-exercise therapy on the MMSE score between the statin-naïve group and pre-existing statin groups. (C) Box-and-whisker plot showing the effect of combined exercise and statin therapy for 5 months on the MMSE scores between patients without DM (non-DM) and those with DM. (D) A regression analysis showing the correlation between changes in the BMI and changes in the MMSE score. (E) Box-and-whisker plot showing the effect of statin-exercise therapy on the MMSE score between the BMI-increased and BMI-decreased groups. (A, B, C, and E) In these box-and-whisker plots, the lines within the boxes represent the median values, the upper and lower lines of the boxes represent the 25th and 75th percentiles, respectively, and the upper and lower bars outside the boxes represent the 90th and 10th percentiles, respectively. MMSE: mini mental state examination, BMI: body mass index, 5 mo: 5 months, n: number of patients in each group