Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease

Abstract Background Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. Methods In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients ( n  = 25) not receiving DBS. Results We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.