DBS Shows No Benefit For Younger Patients With Early-Onset Alzheimer

Jeannie-Marie Leoutsakos, PhD, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine

Jeannie-Marie Leoutsakos, PhD

In a phase IIb trial, patients that were diagnosed with early-onset Alzheimer disease, under the age of 65 years, were not shown to benefit from deep brain stimulation (DBS).¹

The ADvance trial, an exploratory double-blind trial, assessed DBS targeting the fornix compared to sham treatment in 42 patients with mild Alzheimer. Ultimately, the therapy was shown to be safe, but there were no differences between the 2 groups after 1 year. Although, post-hoc analysis suggested a possible benefit in patients older than 65 years.

“Our results suggest that as we look at DBS as a treatment for Alzheimer disease, we should probably focus on those over 65, which is the bulk of people with Alzheimer,” study author Jeannie-Marie Leoutsakos, PhD, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, said in a statement.²

She added, “Over the years there’s been little in the pipeline that is promising for Alzheimer, so there are now plans in the works for a larger trial only including people over 65.”

All 42 patients were implanted with DBS devices, with 12 of them being under 65 years of age with early onset Alzheimer, and 20 patients over 65 years of age. Half of the participants had their devices activated right away, for 2 years (treatment group), and the other half had them activated after 1 year (sham, delayed treatment). The amount of stimulation was similar to what’s used in Parkinson disease—130 Hz between 3 volts and 3.5 volts.

Leoutsakos and colleagues tracked each group’s clinical dementia rating and disease progression with a pair of questionnaires examining word memory, cognitive ability, judgement, and personal care. PET scans were used to track changes in brain structure.

Ultimately, there was no evidence of slowing cognitive decline in those under the age of 65—a tall task, the researchers noted. There was, however, evidence that those older than 65 years may be benefitted by DBS, as they did not show as rapid a decline as those whose device was not turned on. However, the authors noted that a larger trial would be required to confirm this benefit.

The treatment did show a favorable safety profile. There were similar rates of adverse events (AEs) across both trial phases of years 1 and 2 between groups. Serious AEs were reported in 8 participants, with falls, fainting, seizures, infection, and mental agitation reported. However, this safety profile, Leoutsakos and colleagues noted, is similar to that of the currently available therapies for Alzheimer.

As DBS has been an effective therapy for treating the motor symptoms due to Parkinson disease, the research team is hopeful that it could eventually be used in Alzheimer and other neurodegenerative diseases.

However, convincing clinicians to use DBS may take some time. Notably, according to Neepa J. Patel, MD, a movement disorder specialist with the Henry Ford Health System, there has been some hesitancy from physicians with using DBS even in Parkinson, where it has become a staple.

“There is a group of movement disorder specialists and general neurologists who, maybe, came up in an era before DBS and/or in the beginnings of DBS when it was a riskier procedure and have not really embraced its utility in the treatment of Parkinson,” she told NeurologyLive. “They tend to not really encourage patients to seek it out. If anything, maybe, they’d tell them they’re not ready for it when they are entering into the time of their disease where this would be a valuable therapy. It’s not a new therapy by any means—it’s pretty common practice now.”

REFERENCES

1. Leoutsakos JMS, Haijuan Y, Anderson WS, et al. Deep brain stimulation targeting the fornix for mild Alzheimer dementia (the ADvance trial): a

t wo year

follow-up including results of delayed activation. J Alzheimers Dis. 2018;64(2):597-606.

doi

: 10.3233/JAD-180121.

2. Deep Brain Stimulation for Alzheimer’s Not for Everyone [press release]. Baltimore, MD: Johns Hopkins Medicine; Published October 17, 2018. hopkinsmedicine.org/news/newsroom/news-releases/deep-brain-stimulation-for-alzheimers-not-for-everyone. Accessed October 17, 2018.