Project 4: Cognitive Declines in Elderly Patients who Survive Sepsis

Sepsis is known to produce cognitive declines in elderly patients, especially those predisposed to Alzheimer’s Disease and related dementias (ADRD). Such patients also have a higher risk of developing sepsis. Studies are aimed at better understanding how systemic inflammation influences neuroinflammation and cognitive declines.

CCI patients with PICS often develop severe diaphragm and skeletal muscle atrophy and weakness. PICS patients also demonstrate diminished muscle mitochondrial function and accelerated protein catabolism. Muscle dysfunction in PICS is due to many factors including sarcopenia, sepsis, inflammation, proteolysis, apoptosis and inactivity.

Diaphragm weakness can delay patients weaning from mechanical ventilation and increase inflammation and the risk of nosocomial infection. Limb muscle weakness prevents patients from reaching functional activity milestones, delaying rehabilitation and return to normal function.

Despite the seriousness of diaphragm weakness in CCI patients receiving mechanical ventilation, little is known about exercise strategies to treat this dysfunction. We also have limited knowledge about how strength training impacts inflammation, immunosuppression and catabolism in CCI patients. We are conducting a phase I/II randomized trial of specific inspiratory muscle strength training for up to 28 days in 24 ventilated CCI patients to determine if they can respond to a training program previously shown to improve weaning outcome in chronically ventilated patients.

CCI patients also develop profound lower extremity muscle weakness, but little is known about the effectiveness of strength training in these patients. We are also conducting a phase I/II randomized trial of lower extremity strength training in an additional 24 ventilated CCI patients for 28 days.

Following training, muscle biopsies will be obtained from the quadriceps and contrasted between strength-trained and sham groups examining mitochondrial dysfunction, markers of anabolic and catabolic activity and apoptosis.

Both trials also assess the effect of exercise on markers of inflammation, immunosuppression and protein catabolism.

This project will further our understanding of how treating CCI-related muscle weakness with strength training can not only improve muscle function, but can also potentially blunt the inflammation, immunosuppression and catabolism of PICS.

Project 4 Principle Investigators: