Default mode network connectivity in stable vs progressive mild cognitive impairment

J. R. Petrella, F. C. Sheldon, S. E. Prince, Vince Daniel Calhoun, P. M. Doraiswamy

Research output: Contribution to journalArticle

Abstract

Objective: Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline. Methods: fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline. Results: GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p <0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p <0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models. Conclusions: fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for "early" vs "late" MCI, which are associated with different baseline memory scores and different rates of progression and conversion.

Original languageEnglish (US)
Pages (from-to)511-517
Number of pages7
JournalNeurology
Volume76
Issue number6
DOIs
StatePublished - Feb 8 2011
Externally publishedYes

Fingerprint

Alzheimer Disease
Magnetic Resonance Imaging
Dementia
Cognitive Dysfunction
Endophenotypes
Names
Cross-Sectional Studies
Education
Brain

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Default mode network connectivity in stable vs progressive mild cognitive impairment. / Petrella, J. R.; Sheldon, F. C.; Prince, S. E.; Calhoun, Vince Daniel; Doraiswamy, P. M.

In: Neurology, Vol. 76, No. 6, 08.02.2011, p. 511-517.

Research output: Contribution to journalArticle

Petrella, J. R. ; Sheldon, F. C. ; Prince, S. E. ; Calhoun, Vince Daniel ; Doraiswamy, P. M. / Default mode network connectivity in stable vs progressive mild cognitive impairment. In: Neurology. 2011 ; Vol. 76, No. 6. pp. 511-517.
@article{5bba90b5c14e4dd58f4ea43ce8e73435,
title = "Default mode network connectivity in stable vs progressive mild cognitive impairment",
abstract = "Objective: Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline. Methods: fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline. Results: GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p <0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p <0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models. Conclusions: fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for {"}early{"} vs {"}late{"} MCI, which are associated with different baseline memory scores and different rates of progression and conversion.",
author = "Petrella, {J. R.} and Sheldon, {F. C.} and Prince, {S. E.} and Calhoun, {Vince Daniel} and Doraiswamy, {P. M.}",
year = "2011",
month = "2",
day = "8",
doi = "10.1212/WNL.0b013e31820af94e",
language = "English (US)",
volume = "76",
pages = "511--517",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Default mode network connectivity in stable vs progressive mild cognitive impairment

AU - Petrella, J. R.

AU - Sheldon, F. C.

AU - Prince, S. E.

AU - Calhoun, Vince Daniel

AU - Doraiswamy, P. M.

PY - 2011/2/8

Y1 - 2011/2/8

N2 - Objective: Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline. Methods: fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline. Results: GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p <0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p <0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models. Conclusions: fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for "early" vs "late" MCI, which are associated with different baseline memory scores and different rates of progression and conversion.

AB - Objective: Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline. Methods: fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline. Results: GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p <0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p <0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models. Conclusions: fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for "early" vs "late" MCI, which are associated with different baseline memory scores and different rates of progression and conversion.

UR - http://www.scopus.com/inward/record.url?scp=79951589032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951589032&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e31820af94e

DO - 10.1212/WNL.0b013e31820af94e

M3 - Article

C2 - 21228297

AN - SCOPUS:79951589032

VL - 76

SP - 511

EP - 517

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 6

ER -