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Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI.

Lunau L, Mouridsen K, Rodell A, Ostergaard L, Nielsen JE, Isaacs A, Johannsen P, FReJA Consorti - BMJ Open (2012)

Bottom Line: For SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus.For GRE, there were no significant differences between carriers and non-carriers.Significantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes.

View Article: PubMed Central - PubMed

Affiliation: Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT

Objectives: To assess functional changes measured by cerebral blood flow (CBF) in the presymptomatic stage of frontotemporal dementia linked to chromosome 3 (FTD-3) caused by a truncating mutation in CHMP2B.

Design: Case-control study.

Setting: A memory clinic and tertiary referrals centre for dementia and inherited neurodegenerative disorders.

Participants: The authors included 11 presymptomatic CHMP2B mutation carriers and seven first-degree-related family non-carriers. Participants were MRI scanned twice with an interval of 15 months.

Primary and secondary outcome measures: Local functional changes in brain tissue perfusion were measured as CBF with two different MR techniques, gradient echo (GRE) and spin echo (SE), focusing on CBF in all cerebral vessels (GRE) and cerebral capillaries (SE), respectively. As planned, data analysis included co-registration of perfusion images to structural T1 images. Perfusion data were then extracted from seven regions-of-interest, normalised to white matter and statistically compared between carriers and non-carriers.

Results: For SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus. There was no evidence of changes from baseline to follow-up. For GRE, there were no significant differences between carriers and non-carriers.

Conclusions: Significantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes. Comparing SE with GRE, data indicate that FTD-3 vascular pathology might primarily affect brain capillaries.

No MeSH data available.


Related in: MedlinePlus

Boxplots showing capillary (spin echo) regional cerebral blood flow differences at follow-up between presymptomatic mutation carriers and non-carriers (‘dots’ = outliers; *p<0.05 on the likelihood ratio test). CBF, cerebral blood flow.
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fig3: Boxplots showing capillary (spin echo) regional cerebral blood flow differences at follow-up between presymptomatic mutation carriers and non-carriers (‘dots’ = outliers; *p<0.05 on the likelihood ratio test). CBF, cerebral blood flow.

Mentions: On boxplots (figures 2 and 3), there is a trend towards more pronounced group differences on follow-up compared with baseline, though this could not be confirmed through the statistical analysis. One of the non-carriers had a significantly lower CBF than all other subjects in the basal ganglia but not in other regions. There is no explanation for this result. In the non-carriers, there was a tendency to higher estimates of CBF in the second scan for both SE and GRE data. The outlier among mutation carriers in figure 2 is the same subject in all four indicated ROIs. An analysis of the data without this subject did not change the consistency of the results in all regions; although with the relative small group sizes, this subject contributes significantly to the statistical p value.


Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI.

Lunau L, Mouridsen K, Rodell A, Ostergaard L, Nielsen JE, Isaacs A, Johannsen P, FReJA Consorti - BMJ Open (2012)

Boxplots showing capillary (spin echo) regional cerebral blood flow differences at follow-up between presymptomatic mutation carriers and non-carriers (‘dots’ = outliers; *p<0.05 on the likelihood ratio test). CBF, cerebral blood flow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3307039&req=5

fig3: Boxplots showing capillary (spin echo) regional cerebral blood flow differences at follow-up between presymptomatic mutation carriers and non-carriers (‘dots’ = outliers; *p<0.05 on the likelihood ratio test). CBF, cerebral blood flow.
Mentions: On boxplots (figures 2 and 3), there is a trend towards more pronounced group differences on follow-up compared with baseline, though this could not be confirmed through the statistical analysis. One of the non-carriers had a significantly lower CBF than all other subjects in the basal ganglia but not in other regions. There is no explanation for this result. In the non-carriers, there was a tendency to higher estimates of CBF in the second scan for both SE and GRE data. The outlier among mutation carriers in figure 2 is the same subject in all four indicated ROIs. An analysis of the data without this subject did not change the consistency of the results in all regions; although with the relative small group sizes, this subject contributes significantly to the statistical p value.

Bottom Line: For SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus.For GRE, there were no significant differences between carriers and non-carriers.Significantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes.

View Article: PubMed Central - PubMed

Affiliation: Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT

Objectives: To assess functional changes measured by cerebral blood flow (CBF) in the presymptomatic stage of frontotemporal dementia linked to chromosome 3 (FTD-3) caused by a truncating mutation in CHMP2B.

Design: Case-control study.

Setting: A memory clinic and tertiary referrals centre for dementia and inherited neurodegenerative disorders.

Participants: The authors included 11 presymptomatic CHMP2B mutation carriers and seven first-degree-related family non-carriers. Participants were MRI scanned twice with an interval of 15 months.

Primary and secondary outcome measures: Local functional changes in brain tissue perfusion were measured as CBF with two different MR techniques, gradient echo (GRE) and spin echo (SE), focusing on CBF in all cerebral vessels (GRE) and cerebral capillaries (SE), respectively. As planned, data analysis included co-registration of perfusion images to structural T1 images. Perfusion data were then extracted from seven regions-of-interest, normalised to white matter and statistically compared between carriers and non-carriers.

Results: For SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus. There was no evidence of changes from baseline to follow-up. For GRE, there were no significant differences between carriers and non-carriers.

Conclusions: Significantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes. Comparing SE with GRE, data indicate that FTD-3 vascular pathology might primarily affect brain capillaries.

No MeSH data available.


Related in: MedlinePlus