Elsevier

Brain Stimulation

Volume 13, Issue 5, September–October 2020, Pages 1175-1182
Brain Stimulation

LTP-like cortical plasticity predicts conversion to dementia in patients with memory impairment

https://doi.org/10.1016/j.brs.2020.05.013Get rights and content
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Highlights

  • New biomarkers-based criteria for Alzheimer’s disease increase diagnostic accuracy.

  • LTP-like cortical plasticity impairment is a key phenomenon in AD patients.

  • MCI and prodromal AD patients show early impairment of LTP-like cortical plasticity.

  • Patients with impaired LTP have an increased risk to convert to dementia.

Abstract

Background

New diagnostic criteria consider Alzheimer’s disease (AD) as a clinico-biological entity identifiable in vivo on the presence of specific patterns of CSF biomarkers.

Objective

Here we used transcranial magnetic stimulation to investigate the mechanisms of cortical plasticity and sensory-motor integration in patients with hippocampal-type memory impairment admitted for the first time in the memory clinic stratified according to CSF biomarkers profile.

Methods

Seventy-three patients were recruited and divided in three groups according to the new diagnostic criteria: 1) Mild Cognitive Impaired (MCI) patients (n = 21); Prodromal AD (PROAD) patients (n = 24); AD with manifest dementia (ADD) patients (n = 28). At time of recruitment all patients underwent CSF sampling for diagnostic purposes. Repetitive and paired-pulse transcranial magnetic stimulation protocols were performed to investigate LTP-like and LTD-like cortical plasticity, short intracortical inhibition (SICI) and short afferent inhibition (SAI). Patients were the followed up during three years to monitor the clinical progression or the conversion to dementia.

Results

MCI patients showed a moderate but significant impairment of LTP-like cortical plasticity, while ADD and PROAD groups showed a more severe loss of LTP-like cortical plasticity. No differences were observed for LTD-like cortical plasticity, SICI and SAI protocols. Kaplan-Meyer analyses showed that PROAD and MCI patients converting to dementia had weaker LTP-like plasticity at time of first evaluation.

Conclusion

LTP-like cortical plasticity could be a novel biomarker to predict the clinical progression to dementia in patients with memory impairment at prodromal stages of AD identifiable with the new diagnostic criteria based on CSF biomarkers.

Keywords

Alzheimer’s disease
Transcranial magnetic stimulation
Mild cognitive impairment
Memory
Long term potentiation
Biomarker
TMS

Abbreviations

AD
Alzheimer’s Disease
ADD
Alzheimer’s Disease Dementia
cTBS
continuous Theta-Burst Stimulation
iTBS
intermittent Theta-Burst Stimulation
IWG
International Working Group
LTD
long-term depression
LTP
long-term potentiation
MCI
Mild Cogntive Impairment
NIA-AA
National Institute on Aging and Alzheimer’s Association
PROAD
Prodromal Alzheimer’s Disease
rTMS
repetitive Transcranial Magnetic Stimulation
CSF
cerebrospinal fluid
RAVLT
Rey Auditory Verbal Learning Test

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