Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation

Abstract

The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called "brains at risk" for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.

Figure 1

Schematic representation of some TMS measures and protocols of stimulation. Legend (in alphabetic order): ICF: intracortical facilitation; ISI: interstimulus interval; SAI: short-latency afferent inhibition; PAS: paired-associative stimulation; rTMS: repetitive transcranial magnetic stimulation; SICI: short-interval intracortical inhibition; +: facilitatory/excitatory effect; -: inhibitory/suppressive effect.

Figure 2

Flow diagram showing the search strategy, the number of records identified, and the number of included/excluded studies [106]. This figure is reproduced from Moher, David et al. preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339:b2535 (under the Creative Commons Attribution License/public domain).

Figure 3

TMS findings, proposed diagnostic algorithm, and main rTMS effects in VCI. Legend (in alphabetic order): CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; DLPFC: dorsolateral prefrontal cortex; ICF: intracortical facilitation; iSP: ipsilateral silent period; LTP: long-term potentiation; MD: mixed dementia; MEP: motor evoked potential; rMT: resting motor threshold; rTMS: repetitive transcranial magnetic stimulation; SAI: short-latency afferent inhibition; TMS: transcranial magnetic stimulation; VaD: vascular dementia; VCI: vascular cognitive impairment; VD: vascular depression.