Deep brain stimulation for disorders of memory and cognition

Abstract

The next several decades will see an exponential rise in the number of patients with disorders of memory and cognition, and of Alzheimer's disease in particular. Impending demographic shifts, an absence of effective treatments, and the significant burden these conditions place on patients, caregivers, and society, mean there is an urgent need to develop novel therapies. Deep brain stimulation (DBS) is a neurosurgical procedure that is a standard-of-care for many patients with treatment-refractory Parkinson's disease, dystonia, and essential tremor. DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional circuits, including for mood and anxiety disorders. The deficits in Alzheimer's disease and other disorders of memory and cognition are also beginning to be thought of as arising from dysfunction in neural circuits. Such dysfunction may be amenable to modulation using focal brain stimulation. A global experience is now emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine's most urgent priorities.

Figures

Fig. 1

Schematic illustration of the components of the Papez circuit, critical to human memory function. The fornix connects the hippocampus to the mammillary bodies and septal nuclei of the hypothalamus via its postcommissural segment. The mammillary bodies project via the mammillothalamic tract to the anterior nucleus of the thalamus, which, in turn, projects to the cingulate gyrus. Neocortical projections from the cingulate eventually feedback to the hippocampus through the entorhinal cortex, completing the circuit (reproduced with permission from [15])

Fig. 2

Sagittal magnetic resonance imaging (MRI) slice in a patient with Alzheimer’s disease, showing an implanted deep brain stimulation (DBS) lead targeting the fornix (left), and a corresponding sagittal image 3.5 mm lateral to midline showing a schematic projection of the DBS lead and its relationship to the fornix (right). The electrode contacts appear as dark artifacts on MRI. Each DBS lead has 4 contacts and leads were positioned immediately anterior and parallel to the vertical segment of the fornix bilaterally (adapted with permission from [21])