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

Abstract

BackgroundCholinergic 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.MethodsOne 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.ResultsTMS 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).ConclusionsTMS 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.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0423-6) contains supplementary material, which is available to authorized users.

Toward a Glutamate Hypothesis of Frontotemporal Dementia

“…An impairment of ICF has also been observed in sporadic FTD (Burrell et al, 2011; Benussi et al, 2017), confirming how this biomarker may be useful not only to track disease progression, but also to distinguish FTD from other forms of dementias, even in the early disease stages (Benussi et al, 2018a; Padovani et al, 2018).…”

The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders

“…Because of this, it has been widely studied in patients with cognitive impairment . In support of this idea, SAI has been reported to be reduced in PD‐dementia, PD‐mild cognitive impairment, and MSA type C when compared with PD, whereas it is normal in CBS and PSP . Nevertheless, some further comments are needed in this context.…”

“…[77][78][79] In support of this idea, SAI has been reported to be reduced in PD-dementia, 80 PD-mild cognitive impairment, 81 and MSA type C when compared with PD, 82 whereas it is normal in CBS and PSP. 83 Nevertheless, some further comments are needed in this context. First, SAI is also suppressed by the γ-aminobutyric acid (GABA)ergic drugs lorazepam and zolpidem, 79 which means that abnormalities cannot immediately be ascribed to disordered cholinergic function.…”

Cortical Inhibitory Imbalance in Functional Paralysis

“…A TMS figure-of-eight coil (each loop diameter 70 mM -D70 2 coil) connected to a monophasic Magstim Bistim 2 system (Magstim Company, Oxford, United Kingdom) was employed for all TMS paradigms, as previously reported (Benussi et al, 2018a). Motor evoked potentials (MEPs) were recorded from the right and left first dorsal interosseous (FDI) muscles through surface Ag/AgCl electrodes placed in a belly-tendon montage and acquired using a Biopac MP-150 electromyograph (BIOPAC Systems Inc., Santa Barbara, CA, United States).…”