Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis

Mimura, Yu; Nishida, Hana; Nakajima, Shinichiro; Tsugawa, Sakiko; Morita, Shinji; Yoshida, Kazunari; Tarumi, Ryosuke; Ogyu, Kamiyu; Wada, Masataka; Kurose, Shin; Miyazaki, Takahiro; Blumberger, Daniel M.; Daskalakis, Zafiris J.; Chen, Robert; Mimura, Masaru; Noda, Yoshihiro

doi:10.1016/j.neubiorev.2020.12.003

Cited by 60 publications

(35 citation statements)

References 104 publications

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“…We suggest implementing sham or time control conditions in all such studies and measuring reliability statistics of smallest detectable change (SDC) and ICC [ 23 , 24 , 29 ]. Also, in studies where SAI or LAI measurements are compared between different populations (e.g., [ 10 , 11 , 30 , 31 ]), we recommend that multiple assessments be performed on different days to increase precision and thereby improve the sensitivity.…”

Section: Discussionmentioning

confidence: 99%

The distribution and reliability of TMS-evoked short- and long-latency afferent interactions

et al. 2021

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Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) occur when the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) is reduced by the delivery of a preceding peripheral nerve stimulus. The intra-individual variability in SAI and LAI is considerable, and the influence of sample demographics (e.g., age and biological sex) and testing context (e.g., time of day) is not clear. There are also no established normative values for these measures, and their reliability varies from study-to-study. To address these issues and facilitate the interpretation of SAI and LAI research, we pooled data from studies published by our lab between 2014 and 2020 and performed several retrospective analyses. Patterns in the depth of inhibition with respect to age, biological sex and time of testing were investigated, and the relative reliability of measurements from studies with repeated baseline SAI and LAI assessments was examined. Normative SAI and LAI values with respect to the mean and standard deviation were also calculated. Our data show no relationship between the depth of inhibition for SAI and LAI with either time of day or age. Further, there was no significant difference in SAI or LAI between males and females. Intra-class correlation coefficients (ICC) for repeated measurements of SAI and LAI ranged from moderate (ICC = 0.526) to strong (ICC = 0.881). The mean value of SAI was 0.71 ± 0.27 and the mean value of LAI was 0.61 ± 0.34. This retrospective study provides normative values, reliability estimates, and an exploration of demographic and testing influences on these measures as assessed in our lab. To further facilitate the interpretation of SAI and LAI data, similar studies should be performed by other labs that use these measures.

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Section: Discussionmentioning

confidence: 99%

The distribution and reliability of TMS-evoked short- and long-latency afferent interactions

et al. 2021

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“…In particular, the so-called “gluten encephalopathy” seems to be mediated by a vascular inflammation with an aetiology different from that of the cholinergic dysfunction [ 55 ]. This might be a relevant factor to consider for explaining the lack of difference we observed between the two groups regarding SAI, which is known to be reduced in AD (including the early stage) and in amnestic MCI [ 56 ], but not in most patients with VaD [ 57 ] or in those mild vascular cognitive impairment [ 58 ]. Additionally, the fact that central cholinergic fibers do not seem to be affected at this stage does not prevent from the involvement of other neurotransmission pathways, such as glutamate or GABA, that may be implicated in the occurrence of cognitive and mood disorders in CD patients, as observed by previous studies both before and after GFD [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

Lanza

Fisicaro

D’Agate³

et al. 2021

PLoS ONE

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Background Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. Methods Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. Results The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. Conclusions Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called “gluten encephalopathy”, which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

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“…This might open new venues for therapeutic intervention, in this instance, based on anti-inflammatory strategies, as it has been proposed for mood disorders and other neurodegenerative diseases [ 106 – 108 ]. Neurophysiological biomarkers that can be assessed with noninvasive brain stimulation techniques also used for therapeutics should be explored in relation to apathy, its dimensions, and other neuropsychiatric symptoms in AD [ 109 ]. Finally, as a transdiagnostic neurobehavioral syndrome, the understanding of apathy in AD might benefit from the study of apathy in other neurodegenerative diseases and psychiatric conditions and vice-versa.…”

Section: Future Directionsmentioning

confidence: 99%

Revisiting Apathy in Alzheimer’s Disease: From Conceptualization to Therapeutic Approaches

Teixeira

Gonzales

Souza

et al. 2021

Behavioural Neurology

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Apathy is a neurobehavioral syndrome characterized by impaired motivation for goal-directed behaviors and cognitive activity, alongside blunted affect. Apathy is a common neuropsychiatric syndrome in Alzheimer’s disease (AD), with a 5-year prevalence over 70%. Apathy also serves as a prognostic indicator, correlating with the progression of AD. Despite advances in its conceptualization and understanding of its neural basis, there is very limited empirical evidence to support the available strategies for the treatment of apathy in AD. Given its complex pathophysiology, including distinct substrates for different apathy dimensions (affective, cognitive, and behavioral), it is unlikely that a single pharmacological or nonpharmacological strategy will be effective for all cases of apathy in AD. High-quality evidence research is needed to better understand the role of specific strategies aiming at a personalized approach.

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Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis

Cited by 60 publications

References 104 publications

The distribution and reliability of TMS-evoked short- and long-latency afferent interactions

The distribution and reliability of TMS-evoked short- and long-latency afferent interactions

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

Revisiting Apathy in Alzheimer’s Disease: From Conceptualization to Therapeutic Approaches

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