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, V. D.
AU - Doraiswamy, P. M.
N1 - Funding Information:
Dr. Petrella has served on a scientific advisory board for Janssen; has received research support from Avid Radiopharmaceuticals, Inc., Pfizer Inc, Eisai Inc., and the NIH/NIA; and has served as an expert witness in a medico-legal case. Mr. Sheldon has received salary support from Avid Radiopharmaceuticals, Inc. Dr. Prince has received research support from Pfizer Inc. Dr. Calhoun has received research support from the NIH, the National Science Foundation, and the US Department of Energy; has served as a consultant in medico-legal cases; has performed grant reviews for the NIH; has received support for fMRI training courses; and has generated books or book chapters for publishers of various texts. Dr. Doraiswamy has served on scientific advisory boards for AARP, Dana Foundation, Forest Laboratories, Inc., Medivation, Inc., Bristol-Myers Squibb, Accera, Inc., Avid Radiopharmaceuticals, Inc., Sonexa Therapeutics, Inc., Bayer Schering Pharma, the Alzheimer's Foundation, and the Alzheimer's Association; has received funding for travel or speaker honoraria from Otsuka Pharmaceutical Co., Ltd., Bristol-Myers Squibb, the Alzheimer's Association, the NIH, Accera, Inc., Neuroptix Corporation, Neuronetrix, Inc., Medivation, Inc., GE Healthcare, TauRx Pharmaceuticals, Lundbeck Inc., and Forest Laboratories, Inc.; serves on the editorial board of Pharmacotherapy ; is coinventor on a patent assigned to Duke University re: cholinesterase inhibitors for treating disorders in children; receives publishing royalties for The Alzheimer's Action Plan (St. Martin's Press, 2008) and from AARP Magazine; has served as a consultant for Bayer Schering Pharma, Rutgers University, and the NIH (grant reviews); serves on speakers' bureaus for Forest Laboratories, Inc. and Merck Serono; owns stock in Sonexa Therapeutics, Inc.; and receives research support (to Duke University) from Avid Radiopharmaceuticals, Inc., Elan Corporation, Eli Lilly and Company, Neuronetrix, Inc., Medivation, Inc., Bristol-Myers Squibb, Ono Pharmaceutical Co. Ltd., sanofi-aventis, Novartis, GlaxoSmithKline, Forest Laboratories, Inc. Eisai Inc., the NIH (NIA/NIMH/NINDS), NARSAD, American Federation for Aging Research, and the Alzheimer's Drug Discovery Foundation.
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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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 -