Altered functional connectivity in asymptomatic MAPT subjects A comparison to bvFTD

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Abstract

Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods: In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results: The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions: Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.

Original languageEnglish (US)
Pages (from-to)866-874
Number of pages9
JournalNeurology
Volume77
Issue number9
DOIs
StatePublished - Aug 30 2011

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Frontotemporal Dementia
Microtubule-Associated Proteins
Parietal Lobe
Temporal Lobe
Cerebral Cortex
Mutation
Seeds
Atlases
Gyrus Cinguli
Prefrontal Cortex
Atrophy
Dementia
Connectivity
Microtubules
Protein
Case-Control Studies
Magnetic Resonance Imaging
Brain
Genes

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

@article{ab52678175f3488bb28cd64ce884a6d6,
title = "Altered functional connectivity in asymptomatic MAPT subjects A comparison to bvFTD",
abstract = "Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods: In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results: The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions: Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.",
author = "Whitwell, {Jennifer Lynn} and Josephs, {Keith Anthony} and R. Avula and N. Tosakulwong and Weigand, {S. D.} and Senjem, {M. L.} and Vemuri, {Prashanthi D} and Jones, {David T} and Gunter, {J. L.} and M. Baker and Wszolek, {Zbigniew K} and Knopman, {David S} and Rademakers, {Rosa V} and Petersen, {Ronald Carl} and Boeve, {Bradley F} and Jack, {Clifford R Jr.}",
year = "2011",
month = "8",
day = "30",
doi = "10.1212/WNL.0b013e31822c61f2",
language = "English (US)",
volume = "77",
pages = "866--874",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - Altered functional connectivity in asymptomatic MAPT subjects A comparison to bvFTD

AU - Whitwell, Jennifer Lynn

AU - Josephs, Keith Anthony

AU - Avula, R.

AU - Tosakulwong, N.

AU - Weigand, S. D.

AU - Senjem, M. L.

AU - Vemuri, Prashanthi D

AU - Jones, David T

AU - Gunter, J. L.

AU - Baker, M.

AU - Wszolek, Zbigniew K

AU - Knopman, David S

AU - Rademakers, Rosa V

AU - Petersen, Ronald Carl

AU - Boeve, Bradley F

AU - Jack, Clifford R Jr.

PY - 2011/8/30

Y1 - 2011/8/30

N2 - Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods: In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results: The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions: Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.

AB - Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods: In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results: The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions: Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.

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U2 - 10.1212/WNL.0b013e31822c61f2

DO - 10.1212/WNL.0b013e31822c61f2

M3 - Article

C2 - 21849646

AN - SCOPUS:80055088252

VL - 77

SP - 866

EP - 874

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 9

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