Background: The importance of developing unique, neural circuitry-based treatments for the cognitive and neuropsychiatric symptoms of Alzheimer disease (AD) was the impetus for a phase I study of deep brain stimulation (DBS) in patients with AD that targeted the fornix.
Objective: To test the hypotheses that DBS would increase cerebral glucose metabolism in cortical and hippocampal circuits and that increased metabolism would be correlated with better clinical outcomes.
Design: Open-label trial.
Setting: Academic medical center.
Patients: A total of 5 patients with mild, probable AD (1 woman and 4 men, with a mean [SD] age of 62.6 [4.2] years).
Intervention: Deep brain stimulation of the fornix.
Main outcome measures: All patients underwent clinical follow-up and high-resolution positron emission tomography studies of cerebral glucose metabolism after 1 year of DBS.
Results: Functional connectivity analyses revealed that 1 year of DBS increased cerebral glucose metabolism in 2 orthogonal networks: a frontal-temporal-parietal-striatal-thalamic network and a frontal-temporal-parietal-occipital-hippocampal network. In similar cortical regions, higher baseline metabolism prior to DBS and increased metabolism after 1 year of DBS were correlated with better outcomes in global cognition, memory, and quality of life.
Conclusions: Increased connectivity after 1 year of DBS is observed, which is in contrast to the decreased connectivity observed over the course of AD. The persistent cortical metabolic increases after 1 year of DBS were associated with better clinical outcomes in this patient sample and are greater in magnitude and more extensive in the effects on cortical circuitry compared with the effects reported for pharmacotherapy over 1 year in AD.