Dataset Information

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

ABSTRACT:

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.

SUBMITTER: Dopper EG

PROVIDER: S-EPMC5011170 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

Dopper Elise G P EG Chalos Vicky V Ghariq Eidrees E den Heijer Tom T Hafkemeijer Anne A Jiskoot Lize C LC de Koning Inge I Seelaar Harro H van Minkelen Rick R van Osch Matthias J P MJ Rombouts Serge A R B SA van Swieten John C JC

NeuroImage. Clinical 20160803

<h4>Objective</h4>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) i ...[more]

PMID: 27625986

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Project description:BackgroundInvestigating the effect of post-labeling delay (PLD) on regional cerebral blood flow (CBF) in adults and optimizing the PLD for arterial spin-labeling (ASL) magnetic resonance (MR) imaging are important.MethodsPseudo-continuous ASL imaging with a three PLDs protocol was performed in 90 healthy adult volunteers from January 2018 to February 2019. Healthy subjects were divided into youth group (mean age, 30.63 years; age range, 20-44 years), middle-aged group (mean age, 52.16 years; age range 45-59 years) and elderly group (mean age, 66.07 years; age range, 60-77 years). After preprocessing, analyses of variance (ANOVA) and volume-of-interest (VOI) were conducted to compare the CBF in each brain region. According to the trends of CBF changing with PLD and the results of ANOVA, we optimized the PLD for ASL imaging in different brain regions and age groups.ResultsThe CBF values of 87 VOIs [global gray matter (global GM) and other 86 VOIs] for each subject were obtained. Young people had less statistically significant VOIs than middle-aged and elderly people [Numbers of VOIs which had statistical significance (P < .05) in the analysis of ANOVA: 42 (youth group), 79 (middle-aged group), and 71 (elderly group)]. In youth group, the deep GM, occipital lobe and temporal lobe were more affected by PLDs than limbic system, frontal lobe and parietal lobe [VOIs with statistical significance (P < .05)/total VOIs: 8/8 (deep GM) > 8/12 (occipital lobe) > (8/14) (temporal lobe) > 5/12 (limbic system) > 11/28 (frontal lobe) > (2/12) parietal lobe]. In middle-aged group, the limbic system, deep GM and temporal lobe were more affected by PLDs than parietal lobe, frontal lobe and occipital lobe [VOIs with statistical significance (P < 0.05)/total VOIs: 12/12 (limbic system) = 8/8 (deep GM) > (13/14) (temporal lobe) > (11/12) parietal lobe > 25/28 (frontal lobe) > 9/12 (occipital lobe)]. In elderly group, the temporal lobe, parietal lobe, and frontal lobe were more affected by PLDs than occipital lobe, limbic system, and deep GM [VOIs with statistical significance (P < .05)/total VOIs: 14/14 (temporal lobe) > 12/12 (parietal lobe) > 22/28 (frontal lobe) > 9/12 (occipital lobe) > 8/12 (limbic system) > 5/8 (deep GM)]. The optimal PLD for most VOIs in youth group was 1525 ms. However, for middle-aged and elderly group, the optimal PLD for most VOIs was 2525 ms.ConclusionYoung people are less affected by PLDs than middle-aged and elderly people. The middle-aged people are most affected by PLDs. In addition, the spatial distributions of PLD effect were different among the three age groups. Optimizing the PLD for ASL imaging according to age and brain regions can obtain more accurate and reliable CBF values.

Dataset Information

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

Objective

Methods

Results

Interpretation

Publications

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

Similar Datasets

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