Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease

Mario Parra Rodriguez, Ezequiel P. Mikulan, Natalia Trujillo, Sergio Della Sala, Francisco Lopera, Facundo Manes, John M. Starr, Agustín M. Ibáñez

Abstract

Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression.
Original languageEnglish
JournalCurrent Alzheimer Research
StateAccepted/In press - 19 May 2017

Fingerprint

Information Dissemination
Short-Term Memory
Alzheimer Disease
Biological Markers
Brain
brain
connectivity
memory
information flow
patient
Prodromal Symptoms
Electroencephalography
deficit
region
test
method
biomarker
Memory Disorders
objective
assessment

Keywords

  • Alzheimer’s disease
  • Memory binding
  • Brain connectivity
  • Mutual Information
  • EEG
  • Biomarkers
  • PSEN1

Cite this

Parra Rodriguez, Mario; Mikulan, Ezequiel P.; Trujillo, Natalia; Della Sala, Sergio; Lopera, Francisco; Manes, Facundo; Starr, John M.; Ibáñez, Agustín M. / Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease.

In: Current Alzheimer Research, 19.05.2017.

Research output: Contribution to journalArticle

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title = "Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease",
keywords = "Alzheimer’s disease, Memory binding, Brain connectivity, Mutual Information, EEG, Biomarkers, PSEN1",
author = "{Parra Rodriguez}, Mario and Mikulan, {Ezequiel P.} and Natalia Trujillo and {Della Sala}, Sergio and Francisco Lopera and Facundo Manes and Starr, {John M.} and Ibáñez, {Agustín M.}",
year = "2017",
month = "5",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers",

}

Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease. / Parra Rodriguez, Mario; Mikulan, Ezequiel P.; Trujillo, Natalia; Della Sala, Sergio; Lopera, Francisco; Manes, Facundo; Starr, John M.; Ibáñez, Agustín M.

In: Current Alzheimer Research, 19.05.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease

AU - Parra Rodriguez,Mario

AU - Mikulan,Ezequiel P.

AU - Trujillo,Natalia

AU - Della Sala,Sergio

AU - Lopera,Francisco

AU - Manes,Facundo

AU - Starr,John M.

AU - Ibáñez,Agustín M.

PY - 2017/5/19

Y1 - 2017/5/19

N2 - Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression.

AB - Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression.

KW - Alzheimer’s disease

KW - Memory binding

KW - Brain connectivity

KW - Mutual Information

KW - EEG

KW - Biomarkers

KW - PSEN1

M3 - Article

JO - Current Alzheimer Research

T2 - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

ER -