Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep 18;10(1):94.
doi: 10.1186/s13195-018-0423-6.

The impact of transcranial magnetic stimulation on diagnostic confidence in patients with Alzheimer disease

Alberto Benussi  1 , Antonella Alberici  1 , Clarissa Ferrari  2 , Valentina Cantoni  1   3 , Valentina Dell'Era  1 , Rosanna Turrone  1 , Maria Sofia Cotelli  4 , Giuliano Binetti  2 , Barbara Paghera  5 , Giacomo Koch  6   7 , Alessandro Padovani  1 , Barbara Borroni  8
Affiliations

The impact of transcranial magnetic stimulation on diagnostic confidence in patients with Alzheimer disease

Alberto Benussi et al. Alzheimers Res Ther. .

Abstract

Background: Cholinergic dysfunction is a key abnormality in Alzheimer disease (AD) that can be detected in vivo with transcranial magnetic stimulation (TMS) protocols. Although TMS has clearly demonstrated analytical validity, its clinical utility is still debated. In the present study, we evaluated the incremental diagnostic value, expressed in terms of diagnostic confidence of Alzheimer disease (DCAD; range 0-100), of TMS measures in addition to the routine clinical diagnostic assessment in patients evaluated for cognitive impairment as compared with validated biomarkers of amyloidosis.

Methods: One hundred twenty patients with dementia were included and scored in terms of DCAD in a three-step assessment based on (1) demographic, clinical, and neuropsychological evaluations (clinical work-up); (2) clinical work-up plus amyloid markers (cerebrospinal fluid or amyloid positron emission tomographic imaging); and (3) clinical work-up plus TMS intracortical connectivity measures. Two blinded neurologists were asked to review the diagnosis and diagnostic confidence at each step.

Results: TMS measures increased the discrimination of DCAD in two clusters (AD-like vs FTD-like) when added to the clinical and neuropsychological evaluations with levels comparable to established biomarkers of brain amyloidosis (cluster distance of 55.1 for clinical work-up alone, 76.0 for clinical work-up plus amyloid markers, 80.0 for clinical work-up plus TMS). Classification accuracy for the "gold standard" diagnosis (dichotomous - AD vs FTD - variable) evaluated in the three-step assessment, expressed as AUC, increased from 0.82 (clinical work-up alone) to 0.98 (clinical work-up plus TMS) and to 0.99 (clinical work-up plus amyloidosis markers).

Conclusions: TMS in addition to routine assessment in patients with dementia has a significant effect on diagnosis and diagnostic confidence that is comparable to well-established amyloidosis biomarkers.

Keywords: Alzheimer disease; Confidence; Diagnosis; Frontotemporal dementia; PET amyloid; Transcranial magnetic stimulation.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the local ethics committee (NP1965; approved 19 May 2015).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design. CSF Cerebrospinal fluid, DCAD Diagnostic confidence of Alzheimer disease, MRI Magnetic resonance imaging, PET Positron emission tomography, TMS Transcranial magnetic stimulation
Fig. 2
Fig. 2
Mixture model estimation (upper panels) and classification (lower panels; red dots, Alzheimer disease group; black dots, frontotemporal dementia group). DCAD Diagnostic confidence of Alzheimer disease, TMS Transcranial magnetic stimulation
See this image and copyright information in PMC

References

    1. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9:63–75. doi: 10.1016/j.jalz.2012.11.007. - DOI - PubMed
    1. Elahi FM, Miller BL. A clinicopathological approach to the diagnosis of dementia. Nat Rev Neurol. 2017;13:457–476. doi: 10.1038/nrneurol.2017.96. - DOI - PMC - PubMed
    1. Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, Chiotis K, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol. 2017;16:661–676. doi: 10.1016/S1474-4422(17)30159-X. - DOI - PubMed
    1. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–629. doi: 10.1016/S1474-4422(14)70090-0. - DOI - PubMed
    1. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–269. doi: 10.1016/j.jalz.2011.03.005. - DOI - PMC - PubMed

Publication types