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LTP-like cortical plasticity predicts conversion to dementia in patients with memory impairment
Institution:1. Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy;2. Section of Human Physiology, ECampus University, Novedrate, Italy;3. Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy
Abstract:BackgroundNew diagnostic criteria consider Alzheimer’s disease (AD) as a clinico-biological entity identifiable in vivo on the presence of specific patterns of CSF biomarkers.ObjectiveHere 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.MethodsSeventy-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.ResultsMCI 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.ConclusionLTP-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  AD"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"Alzheimer’s Disease  ADD"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"Alzheimer’s Disease Dementia  cTBS"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"continuous Theta-Burst Stimulation  iTBS"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"intermittent Theta-Burst Stimulation  IWG"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"International Working Group  LTD"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"long-term depression  LTP"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"long-term potentiation  MCI"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"Mild Cogntive Impairment  NIA-AA"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"National Institute on Aging and Alzheimer’s Association  PROAD"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"Prodromal Alzheimer’s Disease  rTMS"}  {"#name":"keyword"  "$":{"id":"kwrd0150"}  "$$":[{"#name":"text"  "_":"repetitive Transcranial Magnetic Stimulation  CSF"}  {"#name":"keyword"  "$":{"id":"kwrd0160"}  "$$":[{"#name":"text"  "_":"cerebrospinal fluid  RAVLT"}  {"#name":"keyword"  "$":{"id":"kwrd0170"}  "$$":[{"#name":"text"  "_":"Rey Auditory Verbal Learning Test
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