Symptomatic treatment of memory decline in Alzheimer's disease by deep brain stimulation: a feasibility study

Recent studies have suggested that memory circuits can be modulated by deep brain stimulation (DBS). This propriety might be used to slow down cognitive decline in patients suffering from Alzheimer's disease (AD). We conducted a prospective study to evaluate the feasibility and safety of DBS in AD patients with mild cognitive decline. Inclusion criteria were: patients (<70 years old) with AD diagnosed for less than 2 years, predominant impairment of episodic memory, and Mini-Mental Status Exam (MMSE) score between 20 and 24. The fornix was stimulated bilaterally by electrodes implanted stereotactically in the hypothalamus. Clinical, biological, neuropsychological, and imaging evaluations were conducted 3 months before surgery and 3, 6, and 12 months thereafter. During the one year-period of inclusion, 110 patients with recently diagnosed AD and predominant impairment of episodic memory were screened. Only 9 patients (8.2%) fulfilled all the inclusion criteria. Finally, just one patient accepted to be operated (acceptance rate 11.1%) and completed the study. No complications occurred and the stimulation was perfectly tolerated. After one year of stimulation, the memory scores (MMSE, ADAS-Cog, Free and Cued Selective Reminding Test) were stabilized compared to baseline, and mesial temporal lobes metabolism increased. This pilot study provides new data about the safety of fornix DBS in the hypothalamus. However, it suggests that only a small proportion of AD patients might be interested in this approach and that the acceptance of DBS by AD patients was low, raising questions about the relevance of this approach to meet the expectations of these patients.