Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study
Objective: Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modify...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | NeuroImage: Clinical |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158216301371 |
| _version_ | 1819015195147632640 |
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| author | Elise G.P. Dopper, PhD Vicky Chalos Eidrees Ghariq Tom den Heijer, MD PhD Anne Hafkemeijer, MSc Lize C. Jiskoot, MSc Inge de Koning, PhD Harro Seelaar, MD PhD Rick van Minkelen, PhD Matthias J.P. van Osch, PhD Serge A.R.B. Rombouts, PhD John C. van Swieten, MD PhD |
| author_facet | Elise G.P. Dopper, PhD Vicky Chalos Eidrees Ghariq Tom den Heijer, MD PhD Anne Hafkemeijer, MSc Lize C. Jiskoot, MSc Inge de Koning, PhD Harro Seelaar, MD PhD Rick van Minkelen, PhD Matthias J.P. van Osch, PhD Serge A.R.B. Rombouts, PhD John C. van Swieten, MD PhD |
| author_sort | Elise G.P. Dopper, PhD |
| collection | DOAJ |
| description | Objective: Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF).
Methods: Healthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31).
Results: GRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up.
Interpretation: We demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials. |
| first_indexed | 2024-12-21T02:27:52Z |
| format | Article |
| id | doaj.art-abf522c4ab6b4c6cb0b0804f8f6fcf90 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-21T02:27:52Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-abf522c4ab6b4c6cb0b0804f8f6fcf902022-12-21T19:19:00ZengElsevierNeuroImage: Clinical2213-15822016-01-0112C46046510.1016/j.nicl.2016.08.001Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling studyElise G.P. Dopper, PhD0Vicky Chalos1Eidrees Ghariq2Tom den Heijer, MD PhD3Anne Hafkemeijer, MSc4Lize C. Jiskoot, MSc5Inge de Koning, PhD6Harro Seelaar, MD PhD7Rick van Minkelen, PhD8Matthias J.P. van Osch, PhD9Serge A.R.B. Rombouts, PhD10John C. van Swieten, MD PhD11Department of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsC.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Neuropsychology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam, The NetherlandsC.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neurology, Erasmus Medical Center, Rotterdam, The NetherlandsObjective: Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF). Methods: Healthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31). Results: GRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up. Interpretation: We demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials.http://www.sciencedirect.com/science/article/pii/S2213158216301371Frontotemporal dementiaArterial spin labelingCerebral blood flowPresymptomatic |
| spellingShingle | Elise G.P. Dopper, PhD Vicky Chalos Eidrees Ghariq Tom den Heijer, MD PhD Anne Hafkemeijer, MSc Lize C. Jiskoot, MSc Inge de Koning, PhD Harro Seelaar, MD PhD Rick van Minkelen, PhD Matthias J.P. van Osch, PhD Serge A.R.B. Rombouts, PhD John C. van Swieten, MD PhD Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study NeuroImage: Clinical Frontotemporal dementia Arterial spin labeling Cerebral blood flow Presymptomatic |
| title | Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study |
| title_full | Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study |
| title_fullStr | Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study |
| title_full_unstemmed | Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study |
| title_short | Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study |
| title_sort | cerebral blood flow in presymptomatic mapt and grn mutation carriers a longitudinal arterial spin labeling study |
| topic | Frontotemporal dementia Arterial spin labeling Cerebral blood flow Presymptomatic |
| url | http://www.sciencedirect.com/science/article/pii/S2213158216301371 |
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