P2‐028: The Effect of Statins on Rate of Cognitive Decline in Mild Cognitive Impairment

Abstract

Introduction: This study's aims are to identify whether a relationship between statin use and rate of cognitive decline exists. The relationship between statins and mild cognitive impairment (MCI) has been investigated in the past with the evidence showing mixed results. Methods: Seven hundred sixty-eight subjects were identified with MCI. Subjects were stratified into six possible groups according to apolipoprotein E (APOE) ε4 allele status and statin use and assessed for decline in cognitive function.Results: All cognitive assessments trended toward less decline with statin use. Alzheimer's Disease Assessment Scale 11 (ADAS 11) showed the biggest difference in mean change between statin users and nonusers (20.82 vs. 21.22, respectively). Change reached marginal significance on the ADAS 11 when stratified by APOE ε4-negative subjects. Discussion: All cognitive assessments trended toward less decline when subjects were concurrently treated with a statin, supporting the position that statins do not have a net negative effect on cognitive assessment and suggesting a potential treatment benefit.

Quantitative Systems Pharmacology Model for Alzheimer Disease Indicates Targeting Sphingolipid Dysregulation as Potential Treatment Option

“…Altered lipid metabolism is also associated with several key genetic risk factors for AD, such as APOE, ABCA1, and ABCA7 . Several attempts have been made at targeting lipid metabolism and/or synthesis as treatments for AD, but most have focused on cholesterol as the entry point and have proven unsuccessful either due to severe side effects hindering further development (i.e., liver X receptor agonists) or due to lack of sufficient brain penetration and/or achieved effect size on cholesterol lowering (i.e., simvastatin) …”

“…15,16 Several attempts have been made at targeting lipid metabolism and/or synthesis as treatments for AD, but most have focused on cholesterol as the entry point and have proven unsuccessful either due to severe side effects hindering further development (i.e., liver X receptor agonists 17 ) or due to lack of sufficient brain penetration and/or achieved effect size on cholesterol lowering (i.e., simvastatin). 18,19 A potential alternative targeting mechanism is through sphingolipid modulation. At AbbVie, we developed several compounds, including A-971432, 20 which specifically activate sphingosine-1-phosphate 5 receptor (S1PR5).…”