Transcranial magnetic stimulation treatment in Alzheimer's disease: a meta-analysis of its efficacy as a function of protocol characteristics and degree of personalization.

Alzheimer's disease (AD) represents the most common type of neurodegenerative disorder. Although our knowledge on the causes of AD remains limited and no curative treatments are available, several interventions have been proposed in trying to improve patients' symptomatology. Among those, transcranial magnetic stimulation (TMS) has been shown a promising, safe and noninvasive intervention to improve global cognitive functioning. Nevertheless, we currently lack agreement between research studies on the optimal stimulation protocol yielding the highest efficacy in these patients. To answer this query, we conducted a systematic literature search in PubMed, PsycINFO and Scopus databases and meta-analysis of studies published in the last 10 years (2010-2021) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differently from prior published meta-analytic work, we investigated whether protocols that considered participants-specific neuroimaging scans for the selection of individualized stimulation targets held more successful outcomes compared to those relying on a generalized targeting selection criteria. We then compared the effect sizes of subsets of studies based on additional protocol characteristics (frequency, duration of intervention, number of stimulation sites, use of concomitant cognitive training and patients' educational level). Our results confirm TMS efficacy in improving global cognitive functioning in mild-to-moderate AD patients, but also highlight the flaws of current protocols characteristics, including a possible lack of sufficient personalization in stimulation protocols.