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- Follin, Cecilia, et al.
(författare)
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Hypothalamic dysfunction revealed by magnetic resonance diffusion tensor imaging in childhood leukemia survivors treated with cranial radiotherapy but not in craniopharyngeoma survivors
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background: Metabolic complications with obesity are frequent in childhood acute lymphoblastic leukemia (ALL) survivors treated with cranial radiotherapy (CRT). Childhood onset Craniopharyngioma (CP) survivors without hypothalamic (HT) involvement are spared gross obesity. Magnetic resonance diffusion tensor imaging (DTI) provides information of microstructure function of the brain and quantified as fractional anisotrophy (FA), mean diffusivity (MD), axial and radial diffusivity (AD, RD). Since MD in HT is reportedly impaired (increased) in obese compared to non-obese subjects, we investigated DTI in the HT.Methods: Twenty nine ALL survivors on hormone supplementation were investigated 34 years after CRT (24 Gy). 17 CO-CP survivors with hormone supplementation but without HT damage were investigated. Comparisons were made with these two patient populations to 27 matched controls regarding DTI parameters in the HT and for BMI, fat mass, fat free mass and waist/hip measurements.Results: We recorded reduced FA (0.27 vs 0.29, P=0.04), and increased MD (1.13 vs 1.00, P<0.001), AD (1.41 vs 1.25, P<0.001), and RD (0.99 vs 0.86, P<0.001) in the right HT and increased MD (1.42 vs 1.25, P<0.001), AD (1.75 vs 1.58, P<0.001), and RD (1.25 vs 1.04, P<0.001) in left HT in ALL survivors compared to matched controls. The CPs showed no difference in the HT for these parameters compared to controls. ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with a BMI < 25 and compared to controls with BMI ≥ 25 in the right HT. This was not the case in CP survivors or in controls.Conclusions: Thirty four years after CRT for ALL, DTI measures are deranged in the HT. ALL survivors with a BMI ≥ 25 were presented with worse HT dysfunction. CP survivors were unaffected. The present data suggests changes in the microstructure of the HT in these ALL survivors.
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| 2. |
- Follin, Cecilia, et al.
(författare)
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Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study
- 2019
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Ingår i: Acta Oncologica. - 0284-186X. ; 58:7, s. 1021-1028
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p <.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p <.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p <.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p <.04). The left and right uncinate fasciculus (r = 0.6, p <.001), (r = −0.5, p <.02) as well as the right ventral cingulum (r = 0.5, p <.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.
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| 3. |
- Follin, Cecilia, et al.
(författare)
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Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage
- 2017
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 87:4, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. Design: Case-control study. Patients: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. Measurements: DTI parameters of the HT were measured and body composition. Results: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. Conclusions: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.
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| 4. |
- Jalakas, Mattis, et al.
(författare)
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A quick test of cognitive speed can predict development of dementia in Parkinson’s disease
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) patients frequently develop cognitive impairment. There is a need for brief clinical assessments identifying PD patients at high risk of progressing to dementia. In this study, we look into predicting dementia in PD and underlying structural and functional correlates to cognitive decline in PD. We included 175 patients with PD, 30 with PD dementia, 51 neurologically healthy controls and 121 patients with Alzheimer’s disease (AD) from Skane University Hospital, BIOFINDER cohorts. All underwent cognitive tests, including MMSE, 10-word list delayed recall (ADAS-cog), A Quick Test of cognitive speed (AQT), Letter S fluency, Clock Drawing Test (CDT) and pentagon copying. In non-demented patients with PD, abnormal AQT and CDT results predicted an increased risk of subsequent development of dementia (hazard ratio 2.2 for both). When comparing the cognitive profile between PD and AD, decreased performance on AQT, which measures attention and processing speed, was more typical in PD. Lastly, we investigated the underlying structural and functional correlates for the PD-specific test AQT with magnetic resonance imaging. In PD patients, decreased performance on AQT was associated with i) cortical thinning in temporoparietal regions, ii) changes in diffusion MRI, especially in the cingulum tract, and iii) decreased functional connectivity in posterior brain networks.
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| 6. |
- Svärd, Daniel, et al.
(författare)
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The effect of white matter hyperintensities on statistical analysis of diffusion tensor imaging in cognitively healthy elderly and prodromal Alzheimer’s disease
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Diffusion tensor imaging (DTI) has been used to study microstructural white matter alterations in a variety of conditions including normal aging and Alzheimer’s disease (AD). White matter hyperintensities (WMH) are common in cognitively healthy elderly as well as in AD and exhibit elevated mean diffusivity (MD) and reduced fractional anisotropy (FA). However, the effect of WMH on statistical analysis of DTI estimates has not been thoroughly studied. In the present study we address this in two ways. First, we investigate the effect of WMH on MD and FA in the dorsal and ventral cingulum, the superior longitudinal fasciculus, and the corticospinal tract, by comparing two matched groups of cognitively healthy elderly (n = 21 + 21) with unequal WMH load. Second, we assess the effects of adjusting for WMH load when comparing MD and FA in prodromal AD subjects (n = 83) to cognitively healthy elderly (n = 132) in the abovementioned white matter tracts. Results showed the WMH in cognitively healthy elderly to have a generally large effect on DTI estimates (Cohen’s d = 0.63 to 1.27 for significant differences in MD and −1.06 to −0.69 for FA). These effect sizes were comparable to those of various neurological and psychiatric diseases (Cohen’s d = 0.57 to 2.20 for differences in MD and −1.76 to −0.61 for FA). Adjusting for WMH when comparing DTI estimates in prodromal AD subjects to cognitively healthy elderly improved the explanatory power as well as the outcome of the analysis, indicating that some of the differences in MD and FA were largely driven by unequal WMH load between the groups rather than alterations in normal-appearing white matter (NAWM). Thus, our findings suggest that if the purpose of a study is to compare alterations in NAWM between two groups using DTI it may be necessary to adjust the statistical analysis for WMH.
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