Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report

Frontiers in Aging Neuroscience

María Cabrera¹  Leonides Canuet²  Cristina Nombela³  Juan A. Barcia⁴  Leyre Sanchez-Sanchez-Rojas⁵  María Aurora Viloria⁶  Pedro Gil⁶  Amanda López⁸  Bryan Andrew Strange^1,10  Raquel Yubero^1,12 

[1] 0Servicio de Medicina Nuclear, Hospital Clínico San Carlos, IdISSC, Madrid, Spain;1Departamento de Neurología, Hospital Nuestra Señora del Rosario, Madrid, Spain;2Departamento de Psicología Biológica y de la Salud, Facultad de Psicología, Universidad Autónoma de Madrid, Madrid, Spain;Departamento de Cirugía, Facultad de Medicina, Servicio de Neurocirugía, Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, Spain;Departamento de Medicamentos Veterinarios, Agencia Española del Medicamento y Producto Sanitario, Madrid, Spain;Departamento de Medicina, Facultad de Medicina, Servicio de Geriatría, Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, Spain;Departamento de Neurología, Hospital Quirón Salud, Madrid, Spain;Facultad de Salud, Universidad Internacional de la Rioja, Logroño, Spain;Grupo de Investigación en Neurociencias Aplicadas, Hospital Clínico San Carlos, IdISSC, Madrid, Spain;Laboratory for Clinical Neuroscience, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid, Spain;Unidad de Investigación y Ensayos Clínicos, Instituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, Spain;Universidad Pontificia de Comillas, Madrid, Spain;

关键词: Alzheimer’s disease;    directional deep brain stimulation;    fornix (brain);    clinical trial;    neuropsychology;   

DOI  :  10.3389/fnagi.2022.809972

来源: DOAJ

【 摘 要 】

BackgroundCurrent treatments for Alzheimer’s disease (AD) modulate global neurotransmission but are neither specific nor anatomically directed. Tailored stimulation of target nuclei will increase treatment efficacy while reducing side effects. We report the results of the first directional deep brain stimulation (dDBS) surgery and treatment of a patient with AD in an attempt to slow the progression of the disease in a woman with multi-domain, amnestic cognitive status.MethodsWe aimed to assess the safety of dDBS in patients with AD using the fornix as stimulation target (primary objective) and the clinical impact of the stimulation (secondary objective). In a registered clinical trial, a female patient aged 81 years with a 2-year history of cognitive decline and diagnoses of AD underwent a bilateral dDBS surgery targeting the fornix. Stimulation parameters were set between 3.9 and 7.5 mA, 90 μs, 130 Hz for 24 months, controlling stimulation effects by 18F-fluoro-2-deoxy-D-glucose (18F-FDG) scans (baseline, 12 and 24 months), magnetoencephalography (MEG) and clinical/neuropsychological assessment (baseline, 6, 12, 18, and 24 months).ResultsThere were no important complications related to the procedure. In general terms, the patient showed cognitive fluctuations over the period, related to attention and executive function patterns, with no meaningful changes in any other cognitive functions, as is shown in the clinical dementia rating scale (CDR = 1) scores over the 24 months. Such stability in neuropsychological scores corresponds to the stability of the brain metabolic function, seen in PET scans. The MEG studies described low functional connectivity at baseline and a subsequent increase in the number of significant connections, mainly in the theta band, at 12 months.ConclusionThe dDBS stimulation in the fornix seems to be a safe treatment for patients in the first stage of AD. Effects on cognition seem to be mild to moderate during the first months of stimulation and return to baseline levels after 24 months, except for verbal fluency.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT03290274], identifier [NCT03290274].

【 授权许可】

Unknown