Effects of repetitive Transcranial Magnetic Stimulation in aged rats depend on pre-treatment cognitive status: Toward individualized intervention for successful cognitive aging

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) has shown initial promise in combating age-related cognitive decline and dementia. The nature and severity of cognitive aging, however, varies markedly between individuals. Objective/hypothesis: We hypothesized that the distinct constellation of brain changes responsible for individual differences in cognitive aging might influence the response to rTMS. Methods: Cognitive effects of rTMS were evaluated using a rat model of cognitive aging in which aged rats are classified as Aged-Impaired (AI) or -Unimpaired (AU) relative to young (Y) according to their performance in the Morris water maze. Several weeks later, following presentation of a sample odor in an olfactory recognition task, rats received either sham (Y, n = 9; AU, n = 8; AI, n = 9) or intermittent Theta Burst Stimulation (Y, n = 8; AU, n = 8; AI, n = 9). Memory was tested 24 h later. Results: Recognition memory in the sham and stimulated conditions depended on pre-treatment cognitive status in the aged rats. Y and AU sham rats displayed robust odor recognition, whereas sham-treated AI rats exhibited no retention. In contrast, rTMS treated AI rats showed robust retention, comparable in magnitude to Y, whereas the AU stimulated scored at chance. Conclusion: Our results are consistent with a perspective that the unique neurobiology associated with variability in cognitive aging modulates the response to rTMS. Protocols with documented efficacy in young adults may have unexpected outcomes in aging or neurodegenerative conditions, requiring individualized approaches.