Imagine if Alzheimer’s disease were a road trip. Current treatments act like a GPS system, guiding neurotransmission throughout the brain but lacking precision. What if we could take a more targeted route? Well, that’s where directional deep brain stimulation (dDBS) comes in. In a groundbreaking case report, researchers implanted electrodes in the fornix of a patient’s brain, aiming to slow down the progression of Alzheimer’s. And guess what? It worked! Over 24 months of stimulation, the patient experienced cognitive fluctuations related to attention and executive function patterns. But here’s the exciting part—their brain metabolic function remained stable throughout the treatment! PET scans revealed no significant changes. The intriguing findings also showed a rise in functional connectivity after 12 months of dDBS, particularly in the theta band. Verbal fluency was the only cognition aspect that continued to improve after the stimulation ceased. This case study indicates that fornix stimulation is safe and has mild to moderate effects on cognition in early-stage AD. Intrigued? Discover more about this groundbreaking research by exploring the underlying clinical trial.

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].

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