There is no cure for dementia due to non-Alzheimer’s disease (non-AD), and current treatments are symptomatic. Noninvasive brain stimulation therapies such as transcranial magnetic stimulation (TMS) are increasingly being investigated to improve cognitive function in dementia. We conducted a systematic review to investigate the effectiveness of TMS on cognition in non-AD dementia.

Comprehensive search of databases (Medline, Embase, Cochrane, APA PsycINFO, Web of Science, and Scopus) from 2000 to February 2023 using keywords related to TMS and dementia (PROSPERO, CRD42022326423). Here we report outcomes from randomized controlled trials (RCTs) of TMS on non-AD dementia populations.

In total, 20 RCTs comprised of 660 patients, mean age 62 years (range 46-71). Diagnostic groups include stroke (n=8), Parkinson’s disease (n=6), Frontotemporal dementia (n=3), Huntington’s disease (n=2) and Progressive non-fluent aphasia (n=1). The most common site of stimulation was left (L) dorsolateral prefrontal cortex (DLPFC, n=13); other sites were primary motor cortex (n=2); Right (R) Broca's area, Brodmann area, Contralesional pars triangularis, R Inferior Frontal Gyrus (IFG) (all n=1); and multiple sites in 1 RCT (L and R IFG, L superior frontal gyrus, L DLPFC, L and R right anterior temporal lobe, supplementary motor area, anterior cingulate, and vertex). Studies used both low (1Hz, n=5) and high (50Hz, n=5) frequencies, or other high (5Hz, 10Hz, 20Hz) or combination low/high frequencies. Frequent duration of treatment was 10 days (n=7), range 1-40. Of 20 studies, 19 (95%) demonstrated improvement of global cognition (on MoCA, MMSE) and specific cognitive domains (learning and memory, language, executive function, problem-solving, attention, reaction time). The only RCT with no effect utilized a single session intermittent theta burst stimulation on the LDLPFC on PD patients. Adverse events in 7 studies included headaches (most common), dull skull pain, dizziness, insomnia, fatigue, anxiety, temporary decrease in hearing, and temporary decreased mental clarity.

There is favorable evidence that rTMS improves global and specific cognitive domains in non-AD dementia. Left DLPFC is the most common stimulation site, both low- and high-frequency are utilized, and 10 sessions is frequently used. Further studies are needed to determine optimal TMS treatments in cognitively impaired populations