Published online Jun 15, 2017. doi: 10.4239/wjd.v8.i6.286
Peer-review started: November 6, 2016
First decision: November 30, 2016
Revised: February 17, 2017
Accepted: May 3, 2017
Article in press: May 5, 2017
Published online: June 15, 2017
To test associations between statin use and cognitive impairment in adults with childhood-onset type 1 diabetes (T1D).
In 2010-13, n = 108 middle-aged participants from ongoing observational Pittsburgh Epidemiology of Diabetes Complications Study underwent neurocognitive assessment (mean age and T1D duration of 49 and 41 years, respectively). All were diagnosed with childhood-onset (i.e., prior to age 18) T1D between 1950 and 1980 and were seen within one year of diagnosis at Children’s Hospital of Pittsburgh. Self-reported statin use (yes/no and if yes, name of statin) was collected biennially from parent study baseline (1986-1988) to time of neurocognitive testing. Logistic regression models tested associations between statin use groups and cognitive impairment (defined as having two or more cognitive test scores 1.5SD or worse than published norms) while linear regression models tested associations between statin use groups and cognitive domain z-scores (domains: Verbal IQ, memory, executive function, psychomotor speed, and visuo-construction). All models controlled for education and age. To address confounding by indication, models were repeated using a propensity score for statin use.
Of the 108 participants, 51 reported never using statins. Median duration of statin use among the 57 ever users was 6 years. These 57 ever statin users were split to create two groups (≤ or > median years of statin use): 1-6 years (n = 25), and 7-12 years (n = 32). Compared with never users, using statins 1-6 years tripled the odds of cognitive impairment (OR = 3.16; 95%CI: 0.93-10.72; P = 0.06) and using statins 7-12 years almost quintupled the odds of cognitive impairment (OR = 4.84; 95%CI: 1.63-14.44; P = 0.005). Compared with never users, using statins 1-6 or 7-12 years was related to worse performance in the memory domain (β = -0.52; P = 0.003, and -0.39; P = 0.014, respectively). Adjusting for coronary artery disease, low density lipoprotein cholesterol, and Apo E4 status did not substantially alter results, and none of these covariates were significantly related to cognitive outcomes (all P > 0.05). Propensity score analyses support that associations between poor cognitive outcomes and statin use were not due merely to confounding by indication.
Statin use was associated with cognitive impairment, particularly affecting memory, in these middle-aged adults with childhood-onset T1D, whom at this age, should not yet manifest age-related memory deficits.
Core tip: Animal and cell culture studies show that statins can damage cerebral gray and white matter, thereby affecting cognitive function. Findings from human studies remain controversial; early observational studies reported that statin use negatively affected cognition, especially memory, while more recent studies have not replicated these findings. Even though statins are widely prescribed for people with type 1 diabetes (T1D), only one study to date has examined whether statin use is related to cognitive impairment in this patient population. We propose that deleterious effects statins may exert on cognition may be more pronounced in people with T1D, as these individuals are already at an increased risk of cognitive impairment due to long-term exposure to metabolic dysregulation.