Deep Brain Stimulation of the Nucleus Basalis of Meynert in Early Stage of Alzheimer's Dementia.

ADAS-cog 1⁄4 Alzheimer’s disease Assessment Scale, MMSE 1⁄4Mini Mental Status Examination, RWT 1⁄4 Regensburger Wortschatz Test, WAIS 1⁄4 Wechsler Adult Intelligence Scale, WMS 1⁄4 Wechsler Memory Scale, BDI II 1⁄4 Beck’s Depression Inventory (2nd edition), HAMD 1⁄4 Hamilton Depression Rating Scale, FAST 1⁄4 Florida Apraxia Screening Test. a A lower value represents a better outcome. b A higher value represents a better outcome. The clinical benefit of deep brain stimulation (DBS) has recently been investigated in Alzheimer’s disease (AD) [1]. In this context, the Nucleus basalis of Meynert (NBM) and the fornix are discussed as possible target structures [2e4]. In a recent pilot investigation six patients with AD were treated with DBS of the NBM [5] and 4 of the 6 patients showed stable or even improved cognitive functioning after 12 months indicating a possible benefit of the treatment method. In order to test the hypothesis that younger and less affected patients could benefit more from DBS than patients with advanced AD, stimulation of the NBM was performed at younger age and at an earlier stage of the disease in two patients with AD. The patients (male, 61 and 67 years) underwent the same surgical and stimulation procedure and met all other criteria, except the implementation of the cross-over design, as described in our pilot-study. Nevertheless, these case-reports differ essentially from our previous investigation [5] since both patients presented here are 5 years younger, have a higher level of functioning at baseline and a longer observation period of 26 and 28 months. Stereotactically-guided bilateral implantation of quadripolar electrodes into the NBM was conducted and low-frequency stimulation with 20 Hz was applied. The surgical procedures were well tolerated by both patients and no serious adverse events occurred. The clinical results differed in the course of the follow-up period between the two patients (see Table 1). In the ADAS-cog, patient 1 deteriorated by 7 points after 26 months (lower scores indicate an enhancement of cognitive abilities). In patient 2, results of the ADAS-cog did not change after 28 months. Regarding the memory subtest the scores of both patients remained stable over the 24 and 26 months period, respectively. In the cognitive subscale patient 1 deteriorated by 7 points after 26 months whereas patient 2 showed no changes after 28 months. Regarding the MMSE patient 1 deteriorated by 2 points after 26 months, whereas patient 2 improved by 2 points after 28 months compared to the baseline score. Notably, clock agnosia of patient 1 completely disappeared after stimulation onset. The present results indicate that NBM-DBS performed at an earlier stage of the disease and at younger agemay have a favorable impact on disease progression and cognitive functions as particularly apparent in patient 2. He remained stable in all domains of the ADAS-cog and even improved in the MMSE. An enhancement of cognitive functions throughout the disease is very unusual in patients with AD, especially after such a long follow-up period [6]. Although the results of patient 1 showed a global improvement