TMS Boosts Long-term Memory in Older Adults

Megan Brooks

April 19, 2019

High-frequency transcranial magnetic stimulation (TMS) targeting hippocampal-cortical brain networks can improve age-related decline in long-term memory, new research shows.

Age-related memory loss is due to declining function of the hippocampal brain network.

"Our study is the first to show that the function of this brain network can be improved in older adults with brain stimulation, leading to memory improvement," lead investigator Joel Voss, PhD, associate professor at Northwestern University Feinberg School of Medicine in Chicago, told Medscape Medical News.

"After receiving stimulation, older adults with normal age-related memory decline performed just as well on memory tests as younger adults in their 20s and 30s," said Voss.

The study was published online April 17 in Neurology.

Burgeoning Field

The new study comes on the heels of a study published last week in Nature Neuroscience that showed that short-term (25-minute) low-intensity transcranial alternating current stimulation (tACS) can synchronize brain rhythms and improve working memory performance in older adults.

Voss and colleagues used longer-term (consecutive daily sessions) higher-intensity TMS to improve long-term (recollection) memory.

Fifteen cognitively normal adults (mean age, 72 years; 11 women) participated in the single-blind, sham-controlled experiment. TMS targets in the parietal cortex were individually determined on the basis of fMRI connectivity with the hippocampus.

Recollection and recognition memory were assessed before and after five consecutive daily sessions (20 minutes each) of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design.

At baseline, recollection (but not recognition) was specifically impaired in the older adults compared to a control sample of young adults in their 20s.

Relative to sham, active stimulation led to "robust" improvement in recollection and "weak" improvement in recognition in older adults at the 24-hour assessment.

Relative to baseline, there was on average a 31% improvement in recollection with stimulation, compared with a nonsignificant change with sham. In contrast, there was a nonsignificant 2.8% improvement in recognition with stimulation, compared with a nonsignificant change with sham.

Stimulation-induced improvements in recollection were "highly consistent" among the older adults in the study, and following stimulation, their recollection no longer differed significantly from that of the younger control perticipants.

Recollection remained significantly elevated at roughly 1-week follow-up testing relative to baseline, but there was no significant difference from sham, "indicating that significant gains measured at 24 hours did not persist relative to sham," the authors write.

The investigators note that the findings "demonstrate a causal link between recollection and the hippocampal-cortical network in older adults, thereby supporting the hypothesis that dysfunction of this network with age may lead to memory impairment."

The researchers note that the study was intended to test for selective neural and behavioral target engagement, not to evaluate clinical efficacy.

"This is not ready for clinical treatments," said Voss, "but it is very promising, and our follow-up experiments are testing whether we can achieve more robust and longer-lasting memory improvement, which would then motivate clinical application."

Not Ready for Prime Time

Commenting on the findings for Medscape Medical News, Praveen K. Pilly, PhD, HRL Laboratories Center for Human Machine Collaboration, Malibu, California, said this study adds to a "growing literature on using noninvasive brain stimulation to boost memory function in older adults.

"As the authors themselves mention," added Pilly, "their results are based on a relatively small pool of subjects. For clinical applications, these results will need to replicated with a much bigger sample of subjects.

"Also, in my opinion, we would need to directly compare the neural and behavioral effects of low-intensity tACS and higher-intensity TMS in older adults on the same battery of memory tasks, as the side effects and long-term consequences of sustained higher-intensity noninvasive brain stimulation are not well understood."

There is also a need for animal studies to investigate the in vivo effects of TMS on single neurons in memory regions such as the hippocampus to better understand the underlying mechanisms, as has been done for tACS (Krause et al., Proc Natl Acad Sci. 2019 Mar 19;116:5747-5755).

The study was supported by grants from the National Institute on Aging and the National Institutes of Health and by the Northwestern University Cognitive Neurology and Alzheimer's Disease Center. The authors have disclosed no relevant financial relationships. Pilly is an employee of HRL Laboratories.

Neurology. Published online April 17, 2019. Abstract

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