Prevention of Alzheimer’s by a Multimodal Lifestyle Protocol – Working‐mechanisms for Memory Gains: Mouse‐PAW

Abstract

AbstractBackgroundThe approach of changing multiple lifestyle factors simultaneously targeting different risk factors is expected to have the greatest potential in preventing or delaying the progression of dementia. Nevertheless, it is largely unidentified what are the biological working mechanism underlying the positive findings from clinical trials of multimodal lifestyle interventions.MethodWe have set up a novel protocol to study multimodal lifestyle intervention in mice. The protocol was developed to recapitulate the FINGER (NCT01041989) and MIND‐AD (NCT03249688) clinical trials. In the lifestyle Prevention of Alzheimer’s Working‐mechanisms (PAW) group, mice were given access to running wheels (voluntary exercise), Fortasyn Connect (healthy diet), and they were subjected to cognitive training in an IntelliCage (IC) environment. To separately investigate the effects of an intervention resembling vascular monitoring, a group of mice was given Atorvastatin and Enalapril mixed in the diet. Control mice were housed in normal conditions. We included 12 wild‐type female C57BL/J6 mice six‐months‐of‐age per group. The full intervention lasted for 8 weeks.ResultThe study aimed to evaluate the feasibility of this innovative housing setup that provides a lifestyle intervention for the mice. The housing setup furthermore provides diverse data for individual mice on their learning and physical activity. Definite strengths of the protocol are the minimal need for mouse handling, the possibility of group housing, and that the intervention runs fully in a homecage environment. During the intervention, the PAW group undergoes cognitive training in the form of learning the location (corner) of a bottle from which they receive water (positive reinforcement). Regardless of individual variation in learning different cognitive training paradigms, PAW mice on a group level were able to reduce the error rates (incorrect corner visits) by approximately 25% in all paradigms.ConclusionWe constructed a way of performing multimodal lifestyle intervention in mice in a homecage environment, which provides a platform for detailed mechanistic studies. Moreover, our protocol minimizes stress due to handling and provides quantitative data for both cognitive training and exercise. The future steps involve studying animal models of cognitive decline, Alzheimer’s disease and vascular/metabolic dysfunction to assess mechanisms impacted by lifestyle change.