Abstract
BackgroundThe development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments should be administered as early as possible in the disease course. Transcranial magnetic stimulation (TMS) protocols have demonstrated analytical validity in discriminating different forms of dementia; however, its value in daily clinical practice in MCI subjects is still unknown.ObjectiveTo evaluate the clinical value of TMS compared to amyloid markers on diagnostic confidence and accuracy in MCI subjects, considering clinicians’ expertise.MethodsOne hundred seven MCI subjects were included and classified as MCI-Alzheimer disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), or MCI-other in a three-step process based on (i) demographic, clinical, and neuropsychological evaluation (clinical work-up); (ii) clinical work-up PLUS amyloidosis markers or clinical work-up PLUS TMS measures; and (iii) clinical work-up PLUS both markers. Two blinded neurologists with different clinical expertise were asked to express a diagnostic confidence for each MCI subgroup, and ROC curve analyses were performed at each step.ResultsThe addition of TMS markers to clinical work-up significantly increased the diagnostic confidence for MCI-AD (p = 0.003), MCI-FTD (p = 0.044), and MCI-DLB (p = 0.033) compared to clinical work-up alone, but not for MCI-other (p > 0.05). No significant differences between the add-on effect of TMS and the add-on effect of amyloid markers to clinical work-up were observed (p > 0.732), while the diagnostic confidence further increased when both markers were available. The greater the clinical expertise, the greater the flexibility in considering alternative diagnosis, and the greater the ability to modify diagnostic confidence with TMS and amyloid markers.ConclusionsTMS in addition to routine clinical assessment in MCI subjects has a significant effect on diagnostic accuracy and confidence, comparable to well-established biomarkers of amyloidosis.
Highlights
The development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments should be administered as early as possible in the disease course
We showed that Transcranial magnetic stimulation (TMS) measures, when used on clinical grounds, increase diagnostic confidence of Alzheimer disease (AD), comparable to that reported with established amyloidosis biomarkers [20]
Diagnostic confidence: description of the four Diagnostic Confidence (DC) outcomes and association with arm and raters’ clinical expertise Descriptive statistics of the four outcomes are reported in Additional file 1: Figure S1
Summary
The development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments should be administered as early as possible in the disease course. Transcranial magnetic stimulation (TMS) protocols have demonstrated analytical validity in discriminating different forms of dementia; its value in daily clinical practice in MCI subjects is still unknown. Diagnosis of mild cognitive impairment (MCI) relies on extensive evaluation of cognitive and behavioral performances, and refers to subjects with objective cognitive impairment with only minimal impairment in instrumental activities of daily living, who do not meet the criteria for dementia [1]. Classification of MCI is complicated by the fact that it may be due either to metabolic disorders or to other neurodegenerative disorders, such as preclinical frontotemporal dementia (MCIFTD) or preclinical dementia with Lewy bodies (MCIDLB), or causes not related to progressive neurodegenerative diseases [1]. Clinical criteria state that positivity of one or more biomarkers of brain amyloidosis is associated with a high likelihood of AD in MCI subjects [4]. Decreased levels of Aβ1-42 in the cerebrospinal fluid and/or increased binding of amyloid brain imaging ligands on positron emission tomography are the most established and validated amyloid markers [5,6,7,8], being helpful in increasing the diagnostic confidence in patients with AD among clinicians [9, 10]
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