Diagnosis of Mild Cognitive Impairment Due to Alzheimer’s Disease with Transcranial Magnetic Stimulation

Article type: Research Article

Authors: Padovani, Alessandro^a | Benussi, Alberto^a | Cantoni, Valentina^{a; b} | Dell’Era, Valentina^a | Cotelli, Maria Sofia^c | Caratozzolo, Salvatore^a | Turrone, Rosanna^a | Rozzini, Luca^a | Alberici, Antonella^a | Altomare, Daniele^{d; e} | Depari, Alessandro^f | Flammini, Alessandra^f | Frisoni, Giovanni B.^{d; g; h} | Borroni, Barbara^{a; *}

Affiliations: [a] Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy | [b] Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy | [c] Neurology Unit, Valle Camonica Hospital, Brescia, Italy | [d] Laboratory of Alzheimer’s Neuroimaging and Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [e] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy | [f] Dipartimento di Ingegneria dell’Informazione, University of Brescia, Brescia, Italy | [g] LANVIE–Laboratory of Neuroimaging of Aging, University of Geneva, Geneva, Switzerland | [h] Memory Clinic, University Hospital of Geneva, Geneva, Switzerland

Correspondence: [*] Correspondence to: Barbara Borroni, MD, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy. Tel.: +39 0303995632; E-mail: [email protected].

Abstract: Background:Considering the increasing evidence that disease-modifying treatments for Alzheimer’s disease (AD) must be administered early in the disease course, the development of diagnostic tools capable of accurately identifying AD at early disease stages has become a crucial target. In this view, transcranial magnetic stimulation (TMS) has become an effective tool to discriminate between different forms of neurodegenerative dementia. Objective:To determine whether a TMS multi-paradigm approach can be used to correctly identify mild cognitive impairment (MCI) due to AD (AD MCI). Methods:A sample of 69 subjects with MCI were included and classified as AD MCI or MCI unlikely due to AD (non-AD MCI) based on 1) extensive neurological and neuropsychological evaluation, 2) MRI imaging, and 3) cerebrospinal fluid analysis or/and amyloid PET imaging. A paired-pulse TMS multi-paradigm approach assessing short interval intracortical inhibition-facilitation (SICI-ICF), dependent on GABAergic and glutamatergic intracortical circuits, respectively, and short latency afferent inhibition (SAI), dependent on cholinergic circuits, was performed. Results:We observed a significant impairment of SAI and unimpaired SICI and ICF in AD MCI as compared to non-AD MCI. According to ROC curve analysis, the SICI-ICF / SAI index differentiated AD MCI from non-AD MCI with a specificity of 87.9% and a sensitivity of 94.4%. Conclusions:The assessment of intracortical connectivity with TMS could aid in the characterization of MCI subtypes, correctly identifying AD pathophysiology. TMS can be proposed as an adjunctive, non-invasive, inexpensive, and time-saving screening tool in MCI differential diagnosis.

Keywords: Alzheimer’s disease, dementia, mild cognitive impairment, short interval intracortical inhibition, short latency afferent inhibition, transcranial magnetic stimulation

DOI: 10.3233/JAD-180293

Journal: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 221-230, 2018