Supplement - Early detection and prevention of mild cognitive impairment due to cerebrovascular disease

Abstract: We are proposing a supplement in response to PA-15-122, Administrative Supplements for Common Basic Sociobehavioral Mechanisms and Processes that Facilitate or Impede Self-Management of Chronic Conditions. This supplement is proposed to add to our existing R01, Early Detection and Prevention of Mild Cognitive Impairment (parent student). In the parent study, we are determining the feasibility of intensive cardiovascular disease (CVD) risk factor modification, using a self-management approach in 160 patients (80 randomized to intervention and 80 randomized to standard care) with mild cognitive impairment (MCI) due to CVD (MCI-CVD), as a therapeutic intervention for MCI-CVD. The purpose of this supplement is to explore genetic and pharmacologic factors that potentially interfere with the effectiveness of selfmanagement interventions in patients with MCI-CVD. Even under the best circumstances, all patients do not benefit equally from any intervention. We hypothesize that inflammation-related genes result in decreased impact of self-management interventions for CVD risk reduction. We propose to test this hypothesis by comparing outcomes of the intervention being tested in the parent study between those who do, and do not, have these inflammation-related genes. We further hypothesize that anticholinergic load related to the use of polypharmacy in patients with CVD has a negative impact on cognitive function regardless of intervention to improve MCI. There is growing evidence that many drugs used in patients with chronic conditions exert an anticholinergic effect that can be substantial, and that a major consequence is impaired cognitive function. To test this hypothesis we will carefully determine anticholinergic load and compare cognitive function before and after intervention by anticholinergic burden score. All patients enrolled in the parent study will be asked, after IRB approval is obtained, to participate in data collection (review of medical and pharmacy records, and saliva for genetic testing) for the proposed study. Our experience with similar supplemental studies involving collection of genetic material suggests a refusal rate of less than 5%. This study has the potential to illuminate important pharmacologic and genetic variables influencing the effectiveness of self-management interventions in patients with MCI-CVD, a rapidly increasing, burdensome, and expensive condition