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 language | English (US) |
|---|---|
| Pages (from-to) | 511-517 |
| Number of pages | 7 |
| Journal | Neurology |
| Volume | 76 |
| Issue number | 6 |
| DOIs | |
| State | Published - Feb 8 2011 |
| Externally published | Yes |
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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 journal › Article
}
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.
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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 -