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Cortical plasticity assessment predicts decline in patients with mild cognitive impairment
Author(s) -
Lorenzo Francesco Di,
Motta Caterina,
Bonnì Sonia,
Caltagirone Carlo,
Martorana Alessandro,
Koch Giacomo
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044077
Subject(s) - long term potentiation , dementia , neuroscience , neuropsychology , neuroplasticity , medicine , transcranial magnetic stimulation , synaptic plasticity , cognitive decline , memory clinic , neurophysiology , psychology , hippocampal formation , disease , cognition , stimulation , receptor
Background Alzheimer`s disease (AD) is characterized by loss of synaptic connections, cell death and disruption of structural and functional networks. One of the most consistent findings is the impairment of cortical plasticity, especially Long Term Potentiation (LTP) mechanisms. Recently, the use of new diagnostic criteria allowed to considered AD as a clinico‐biological entity identifiable in vivo on the presence of biomarkers. In light of these new criteria, aim of the current work is to investigate cortical plasticity in patients with hippocampal type memory impairment admitted for the first time in the memory clinic and stratified according to CSF biomarkers profile; moreover we followed patients up to a period of three years to explore the relationship between neurophysiological, neuropsychological and CSF biomarkers and clinical progression. Method Seventy‐three patients were recruited and followed up for 36 months. They underwent CSF sampling and Transcranial Magnetic Stimulation to investigate LTP and intracortical circuits. According to the new AD criteria we divided patients in three groups: 1) Mild Cognitive Impaired (MCI) patients (n=21); Prodromal AD (PROAD) patients (n=24); AD Dementia (ADD) patients (n=28). Result In neurophysiological evaluations only iTBS protocol was different among the different groups showing a paradoxical reversal of LTP for ADD and PROAD and a poor response for MCI patients. ProAD worsened faster than MCI. Regression analyses showed that LTP impairment was related to clinical progression. Kaplan‐Meyer analyses showed that patients expressing the worst LTP values were the ones to progress faster in a 3 year time. Conclusion The new criteria based on the presence of biomarkers and dementia allow us to identify patients at a prodromal stage that will develop dementia due to AD. LTP impairment drives the clinical progression in patients at prodromal stages confirming its pivotal role in determining cognitive decline. These results pave the way for the identification of new therapeutic targets such as synaptic plasticity modulators.