BACKGROUND: Dementia represents one of the most challenging health problems. Despite intense research, available therapies have thus far only achieved modest results. Deep brain stimulation (DBS) is an effective treatment option for some movement disorders and is under study for psychiatric applications. Recently, diencephalic DBS revealed selective effects on memory functions, another facet of subcortical DBS. OBJECTIVE: To report a new DBS strategy for the modification of cognitive functions in a patient with severe Parkinson-dementia syndrome. DESIGN: Prospective study with double-blinded sham stimulation period. SETTING: Departments of Stereotaxy and Functional Neurosurgery and Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. PATIENT: A 71-year-old man with slowly progressive Parkinson-dementia syndrome. Intervention We inserted 2 electrodes into the nucleus basalis of Meynert in addition to electrodes in the subthalamic nucleus. Main Outcome Measure Improvement of cognitive functions. RESULTS: Turning on the subthalamic nucleus electrodes improved motor symptoms but left cognitive performance almost unchanged. Turning on electrical stimulation of the nucleus basalis of Meynert resulted in markedly improved cognitive functions. The improvement in attention, concentration, alertness, drive, and spontaneity resulted in the patient's renewed enjoyment of former interests and enhanced social communication. CONCLUSIONS: Such a broad effect on cognition is consistent with ample experimental evidence revealing that the nucleus basalis of Meynert provides cholinergic innervation to the cortical mantle, complemented by glutaminergic and gamma-aminobutyric acid-transmitting projections from the basal forebrain. These projections provide background tuning facilitating cortical operations. Furthermore, nucleus basalis of Meynert stimulation paired with sensory stimuli can accomplish persistent reorganization of specific processing modules. The improvements in cognitive and behavioral performance in our patient are likely to be related to the effects of stimulating residual cholinergic projections and cell bodies in the nucleus basalis of Meynert.
BACKGROUND:Dementia represents one of the most challenging health problems. Despite intense research, available therapies have thus far only achieved modest results. Deep brain stimulation (DBS) is an effective treatment option for some movement disorders and is under study for psychiatric applications. Recently, diencephalic DBS revealed selective effects on memory functions, another facet of subcortical DBS. OBJECTIVE: To report a new DBS strategy for the modification of cognitive functions in a patient with severe Parkinson-dementia syndrome. DESIGN: Prospective study with double-blinded sham stimulation period. SETTING: Departments of Stereotaxy and Functional Neurosurgery and Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. PATIENT: A 71-year-old man with slowly progressive Parkinson-dementia syndrome. Intervention We inserted 2 electrodes into the nucleus basalis of Meynert in addition to electrodes in the subthalamic nucleus. Main Outcome Measure Improvement of cognitive functions. RESULTS: Turning on the subthalamic nucleus electrodes improved motor symptoms but left cognitive performance almost unchanged. Turning on electrical stimulation of the nucleus basalis of Meynert resulted in markedly improved cognitive functions. The improvement in attention, concentration, alertness, drive, and spontaneity resulted in the patient's renewed enjoyment of former interests and enhanced social communication. CONCLUSIONS: Such a broad effect on cognition is consistent with ample experimental evidence revealing that the nucleus basalis of Meynert provides cholinergic innervation to the cortical mantle, complemented by glutaminergic and gamma-aminobutyric acid-transmitting projections from the basal forebrain. These projections provide background tuning facilitating cortical operations. Furthermore, nucleus basalis of Meynert stimulation paired with sensory stimuli can accomplish persistent reorganization of specific processing modules. The improvements in cognitive and behavioral performance in our patient are likely to be related to the effects of stimulating residual cholinergic projections and cell bodies in the nucleus basalis of Meynert.
Authors: J Kuhn; K Hardenacke; D Lenartz; T Gruendler; M Ullsperger; C Bartsch; J K Mai; K Zilles; A Bauer; A Matusch; R-J Schulz; M Noreik; C P Bührle; D Maintz; C Woopen; P Häussermann; M Hellmich; J Klosterkötter; J Wiltfang; M Maarouf; H-J Freund; V Sturm Journal: Mol Psychiatry Date: 2014-05-06 Impact factor: 15.992