Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report
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 brai...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.809972/full |
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| author | Juan A. Barcia María Aurora Viloria Raquel Yubero Raquel Yubero Leyre Sanchez-Sanchez-Rojas Leyre Sanchez-Sanchez-Rojas Amanda López Amanda López Bryan Andrew Strange María Cabrera Leonides Canuet Pedro Gil Cristina Nombela Cristina Nombela |
| author_facet | Juan A. Barcia María Aurora Viloria Raquel Yubero Raquel Yubero Leyre Sanchez-Sanchez-Rojas Leyre Sanchez-Sanchez-Rojas Amanda López Amanda López Bryan Andrew Strange María Cabrera Leonides Canuet Pedro Gil Cristina Nombela Cristina Nombela |
| author_sort | Juan A. Barcia |
| collection | DOAJ |
| description | 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]. |
| first_indexed | 2024-04-12T22:42:58Z |
| format | Article |
| id | doaj.art-c65d0f6fd71443a2bd291c019cbd8330 |
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| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-12T22:42:58Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-c65d0f6fd71443a2bd291c019cbd83302022-12-22T03:13:38ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-04-011410.3389/fnagi.2022.809972809972Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case ReportJuan A. Barcia0María Aurora Viloria1Raquel Yubero2Raquel Yubero3Leyre Sanchez-Sanchez-Rojas4Leyre Sanchez-Sanchez-Rojas5Amanda López6Amanda López7Bryan Andrew Strange8María Cabrera9Leonides Canuet10Pedro Gil11Cristina Nombela12Cristina Nombela13Departamento de Cirugía, Facultad de Medicina, Servicio de Neurocirugía, Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Servicio de Geriatría, Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, SpainDepartamento de Neurología, Hospital Quirón Salud, Madrid, SpainUniversidad Pontificia de Comillas, Madrid, SpainGrupo de Investigación en Neurociencias Aplicadas, Hospital Clínico San Carlos, IdISSC, Madrid, SpainDepartamento de Medicamentos Veterinarios, Agencia Española del Medicamento y Producto Sanitario, Madrid, SpainUnidad de Investigación y Ensayos Clínicos, Instituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, SpainFacultad de Salud, Universidad Internacional de la Rioja, Logroño, SpainLaboratory for Clinical Neuroscience, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid, Spain0Servicio de Medicina Nuclear, Hospital Clínico San Carlos, IdISSC, Madrid, Spain1Departamento de Neurología, Hospital Nuestra Señora del Rosario, Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Servicio de Geriatría, Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, SpainGrupo de Investigación en Neurociencias Aplicadas, Hospital Clínico San Carlos, IdISSC, Madrid, Spain2Departamento de Psicología Biológica y de la Salud, Facultad de Psicología, Universidad Autónoma de Madrid, Madrid, SpainBackgroundCurrent 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].https://www.frontiersin.org/articles/10.3389/fnagi.2022.809972/fullAlzheimer’s diseasedirectional deep brain stimulationfornix (brain)clinical trialneuropsychology |
| spellingShingle | Juan A. Barcia María Aurora Viloria Raquel Yubero Raquel Yubero Leyre Sanchez-Sanchez-Rojas Leyre Sanchez-Sanchez-Rojas Amanda López Amanda López Bryan Andrew Strange María Cabrera Leonides Canuet Pedro Gil Cristina Nombela Cristina Nombela Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report Frontiers in Aging Neuroscience Alzheimer’s disease directional deep brain stimulation fornix (brain) clinical trial neuropsychology |
| title | Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report |
| title_full | Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report |
| title_fullStr | Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report |
| title_full_unstemmed | Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report |
| title_short | Directional DBS of the Fornix in Alzheimer’s Disease Achieves Long-Term Benefits: A Case Report |
| title_sort | directional dbs of the fornix in alzheimer s disease achieves long term benefits a case report |
| topic | Alzheimer’s disease directional deep brain stimulation fornix (brain) clinical trial neuropsychology |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.809972/full |
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