Evaluation of brain iron content in Egyptian Patients with Sickle cell disease and its impact on Neurocognitive functions

Abstract Background Sickle cell disease (SCD) is considered the most prevalent monogenic diseases worldwide. Iron overload is one of the major complications in those patients, especially who in need for frequent transfusion, affecting many organs including the brain. MRI is a valuable, reliable and non-invasive method for quantifying iron concentration in many organs as the liver and heart and it is now used for monitoring of the chelation therapy in SCD patients. Several studies began reporting differences in global cognitive function, particularly for children with SCD, they are at a high risk for neurocognitive impairment they often scored lower on general IQ measures than healthy children which is due to iron overload in brain tissue from the chronic transfusions which can lead to strokes and may be a silent stroke. Objective The current study assessed brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI study in SCD patients in comparison to age and sex-matched healthy controls. Methods A case-control study recruited 32 patients with SCD and 11 healthy controls. Brain MRI study using multi-echo fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated for only 15 SCD patients and the 11 controls. All recruited SCD patients and controls were examined for the neurocognitive functions by these tests: Wechsler IV Intelligence Scale for Adult shows (Verbal, Perceptual, Memory, Processing and Total IQ), their all normal values between 90 – 110. Benton Visual Retention Test have cut of point at (> 4 or = 4). Those values are the same for the difference between the obtained correct and the expected correct, and the difference between the obtained error and expected error. Results The fifteen patient with SCD who underwent brain MRI were age and sex matched with the eleven healthy control (15 SCD patients: mean-age: 16.93 ± 3.41 years, 40.6% females and 11healthy controls: mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. As regards the brain MRI, there was no statistically significant differences between SCD and control group in all regions of interests (p > 0.05). Our study showed that 72.7% of our SCD patients had under threshold TIQ scores. Also18% of the patients showed moderate anxiety, 9% mild anxiety and 9% showed severe anxiety. Conclusion The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur.

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Non-invasive Quantitative MRI assessment of brain iron overload in patients with BThalassemia and Sickle cell disease

QJM ◽

10.1093/qjmed/hcab106.023 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Ghada Samir Ibrahim ◽

Fatma Soliman Elsayed Ebeid ◽

Hend Galal Eldeen Mohammed Ahmed Samir Ibrahim

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Chelation Therapy ◽

Brain Mri ◽

Control Group ◽

Healthy Controls ◽

Brain Iron ◽

Cell Disease ◽

Mri Study ◽

Age And Sex

Abstract Background B-Thalassemia, sickle cell disease (SCD) and other inherited hemoglobin disorders are considered the most prevalent monogenic diseases worldwide. Secondary iron overload is one of the major complications in such groups of patients affecting many organs (e.g. liver, heart and endocrinal glands). Objective The current study will assess brain iron content ( using R2* values ) in the caudate and thalamic regions through quantitative brain MRI study in B-Thalassemia and SCD patients in comparison to age and sex-matched healthy controls. Also evaluation of the association with LIC (liver iron concentrations) and MIC (myocardial iron concentrations) was done. Methods A case control study on 30 patients (15 with B-thalassemia major and 15 with SCD) and 11 age and sex-matched healthy controls was carried out in the period between August 2018 till August 2019. Brain MRI study using multiecho fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. Also brain R2* values were correlated with the LIC and HIC in B-thalassemia and SCD groups. Results 15 transfusion dependent B-thalassemia (mean-age: 19.40 ± 4.31 years, 53.3% females), 15 SCD patients (SCD; mean-age: 16.93 ± 3.41 years, 40.6% females) and 11 age and sex matched healthy controls (HC; mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. No statistically significant differences were found between SCD and control group in all regions of interests No statistically significant differences were found between the three subgroups (p > 0.05) in right thalamus, left and right caudate regions. However, in B-thalassemia subgroup, patients had moderately significantly higher R2* values compared to the controls and SCD patients as regards the left thalamic region with mean R2* values (16.69 ± 1.34) Hz compared to (15.65 ± 1.10) Hz in the control group (p = 0.021) and (15.79 ± 0.77) Hz in the SCD group (p = 0.029). There were no significant correlations between LIC and HIC with brain R2* values of all regions of interests in both B-thalassemia and SCD subgroups. Conclusion MRI is a valuable, reliable, safe and noninvasive method for quantifying iron concentration (in cases of iron overload) in many organs as the liver and heart and it is now used internationally for regular follow up of LIC and HIC for monitoring of the chelation therapy in B-thalassemia and SCD patients. The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur. This may be explained by heavy chelation therapy regimens given to our patients due to their poor compliance so as to keep the pre-transfusion hemoglobin level above 10mg/dl to prevent detrimental cardiac affection as cardiac siderosis, arrhythmias including heart block, or even heart failure.

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Hidden Brain iron content in Sickle cell disease: Impact on Neurocognitive Functions

10.21203/rs.3.rs-399346/v1 ◽

2021 ◽

Author(s):

Mohsen Saleh ElAlfy ◽

Ahmed Samir Ibrahim ◽

Ghada Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein ◽

Hend Galal Eldeen Mohammed ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Brain Mri ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Dysfunction ◽

Neurocognitive Functions

Abstract Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30±0.12 mg/kg/day. 68.9% of SCD had under- threshold IQ, 12.5% had moderate to severe anxiety and 60.8% had depression. There was no differences between SCD, BTM and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p=0.032). Mean right caudate R2* was higher in female than male (p=0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, negative correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients. Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload.

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Brain Iron Content in Egyptian Patients with Sickle Cell Disease: Impact on Neurocognitive Functions

Blood ◽

10.1182/blood-2020-139168 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-37

Author(s):

Mohsen Saleh Elalfy ◽

Ahmed Smair ◽

Ghada Samir ◽

Hanaa Hussein ◽

Hend Mohammed ◽

...

Keyword(s):

Young Adults ◽

Sickle Cell Disease ◽

Iron Overload ◽

Negative Correlation ◽

Iron Content ◽

Brain Mri ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Functions ◽

Left Caudate

Background:Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment which may be due to iron overload in brain tissue or hemoglobin polymerization and endothelial dysfunction.Primary objectivewas measuring brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI in Egyptian adolescents and young adults with multi-transfused SCD in comparison to beta thalassemia major (BTM) and age- and sex-matched healthy controls.Secondary objectiveswere evaluating the impact of brain iron content on neurocognitive functions of SCD patients and its association with MRI assessment of liver iron concentration (LIC) and cardiac iron (myocardial T2*).Methods: 32 children and young adults with SCD (mean age: 15.3 ± 3.7, 19 males and 13 females), 15 BTM (mean age: 19.4 ± 4.3, 7 males and 8 females) and 11 healthy control age- and gender-matched were recruited. Thorough clinical assessment, hematological and serum ferritin were performed. Brain MRI study using multi-echo fast gradient echo sequence was performed only for 15 patients with SCD, 15 patients with BTM and 11 controls and brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. LIC and myocardial T2 were performed for; 15 with SCD and 15 with BTM. 32 SCD patients were examined for the neurocognitive functions; Wechsler IV Intelligence scale (verbal, perceptual, memory, processing and total IQ), Benton Visual Retention Test and Brief Psychiatric Rating Scale (BPRS).Results:For SCD patients their mean transfusion index was 174.70±63.98ml/kg/year and mean iron overload/day 0.30±0.12 mg/kg. 30 (93.8%) all SCD patients were on regular chelation therapy; 16 were on deferiprone and 16 were on combined chelation over last 5 years. Of those 32 SCD patients; 20 received concomitantly hydroxyurea therapy. Mean total IQ for SCD patients was 86.9±10.7; 68.9% had under- threshold <90 IQ and 27.5% had average (90-109) IQ. 12.5% of SCD patients had moderate to severe anxiety and 60.8% had of SCD patients had depression. No significant differences were found between SCD, BTM as regards LIC (p=0.102) No significant differences were found between SCD, BTM and control group in all regions of interests in brain MRI except that left thalamus R2* higher in BTM patients than both SCD and controls (p=0.032). R2* values of different regions of brain in relation with the studied parameters of SCD patients was not significant except that mean right caudate R2* was higher in female 17.4±0.8 than male 15.6±1.7 (p=0.044). The correlation coefficients showed no significant association between brain R2* and LIC or heart R2* values of SCD patients. There were positive correlation between left caudate R2* and both age and HbS%, negative correlation between transfusion index and right thalamus R2*, negative correlation between HbA% and left caudate R2* among SCD patients.Conclusion:Brain iron content in adolescents and young adults with SCD was not significantly different from either controls or BTM; SCD had high prevalence of neurocognitive dysfunction, which could not be explained by brain iron content or distribution. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Hidden brain iron content in sickle cell disease: impact on neurocognitive functions

European Journal of Pediatrics ◽

10.1007/s00431-021-04189-7 ◽

2021 ◽

Author(s):

Mohsen Saleh Elalfy ◽

Ahmed Samir Ibrahim ◽

Ghada Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein ◽

Hend Galal Eldeen Mohammed ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Iron Content ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Functions ◽

Disease Impact

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Brain iron content in systemic iron overload: A beta-thalassemia quantitative MRI study

NeuroImage Clinical ◽

10.1016/j.nicl.2019.102058 ◽

2019 ◽

Vol 24 ◽

pp. 102058 ◽

Cited By ~ 2

Author(s):

Renzo Manara ◽

Sara Ponticorvo ◽

Immacolata Tartaglione ◽

Gianluca Femina ◽

Andrea Elefante ◽

...

Keyword(s):

Iron Overload ◽

Iron Content ◽

Quantitative Mri ◽

Beta Thalassemia ◽

Brain Iron ◽

Mri Study

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Analysis on the MRI and BAEP Results of Neonatal Brain with Different Levels of Bilirubin

10.21203/rs.3.rs-17458/v2 ◽

2020 ◽

Author(s):

LU ZHONGXING ◽

SHOULING DING ◽

FEN WANG ◽

Haitao Lv

Keyword(s):

Central Nervous System ◽

Brain Mri ◽

Full Term ◽

Normal Brain ◽

Central Nervous System Damage ◽

Severe Group ◽

The Difference ◽

The Brain ◽

Abnormal Ratio ◽

Abnormal Brain

Abstract Background：To explore whether there is abnormality of neonatal brains’ MRI and BAEP with different bilirubin levels, and to provide an objective basis for early diagnosis on the bilirubin induced subclinical damage on brains.Methods: To retrospectively analyze the clinical data of 103 neonatal patients, who had been hospitalized in Neonatology Department of Taicang First People’s Hospital from March 2013 to September 2015, to conduct routine brain MRI examination , BAEP testing and to analyze BAEP and MRI image results of the neonatal patients, who were divided into three groups based on the levels of total serum bilirubin concentration (TSB), 16 cases in mild group (TSB:0.0~229.0μmol/L), 49 cases in moderate group (TSB: 229.0~342.0μmol/L) and 38 cases in severe group (TSB≥342.0μmol/L); Results: We found as follows: A. Comparison of the bilirubin value of the different group : 1. The bilirubin value of the mild group is 171.99±33.50 μmol/L, the moderate group is293.98±32.09 μmol/L, and the severe group is 375.59±34.25 μmol /L . And the comparison of bilirubin values of the three groups of neonates (P＜0.01) indicates the difference is statistically significant (P＜0.01). 2. The bilirubin value of the pre-term group is 289.70±85.38μmol/Land the full-term group is 310.36±72.32 μmol/L, but the comparison of the bilirubin values between pre-term group and full-term group indicates that the difference is not statistically significant (P＞0.05).3. The bilirubin value of the normal brain MRI group(82) is 305.55±74.54 μmol/L and the abnormal brain MRI group is 303.56±83.04μmol/L; the comparison of bilirubin values between the two groups indicates that the difference is not statistically significant(P＞0.05). B. The weight value of the ﹤2500g group is 2.04±0.21 and the ≥2500ggroup is 3.39±0.46; the weight comparison of the two groups indicates that the difference is statistically significant (P＜0.01). C. Comparison of the abnormal MRI of the different groups: 1.The brain MRI result's abnormal ratio of the mild group is 31.25%, the moderate group is 16.33% and the severe group is 21.05%, but the comparison of brain MRI results of the three neonates groups indicates that the difference is not statistically significant (P＞0.05). 2.The brain MRI result's abnormal ratio of the pre-term is 30.77% and the full-term group is 16.88%, but the comparison of brain MRI results between prem-term group and full-term group indicates that the difference is not statistically significant (P＞0.05). 3.The brain MRI result's abnormal ratio of the ﹤2500g group is 37.50% and the ≥2500g group is 17.24%; but the comparison of brain MRI results of two neonates groups indicates that the difference is not statistically significant(P＞0.05). D. Comparison of abnormal MRI signal values of globus pallidus on T1WI in different groups: 1. The comparison of normal group signal values with that of mild group (p < 0.05), with that of moderate group and with that of severe group (p < 0.01) indicates that the difference is statistically significant; 2. The comparison of signal values between mild and moderate groups (p < 0.05) and between mild group and severe group (p < 0.01) indicates that the difference is statistically significant; 3. The comparison of signal values between moderate group and severe group indicates that the difference is statistically significant(p < 0.05). E. Comparison of BAEP testing results in groups: 1. There were 27(26.21%) cases in abnormalities of the BAEP results of all 103cases bilirubin patients. 2. There were 15(18.29%) cases in abnormalities of the BAEP result of the 82 cases normal brain MRL , 2(40%) cases in abnormalities of the BAEP result of the 5 cases abnormal MRI in mild bilirubin group, 4（50%） cases in abnormalities of the BAEP result of the 8 cases abnormal MRI in moderate bilirubin group and 6（75%）cases in abnormalities of the BAEP result of the 8 cases abnormal brain MRI in severe bilirubin group. 3. After one month review of the BAEP result, there was 0（0.00%） abnormal case in the normal MRI and the mild group; there were 1（20%） abnormal case in the moderate group and 2（25%） cases in the severe group. Conclusion: At low level of bilirubin, central nervous system damage may also occur and can be detected as abnormality by MRI and BAEP. Meanwhile, MRI and BAEP can also provide early abnormal information for the judgment of central nervous system damage of the children with NHB who have no acute bilirubin encephalopathy (ABE) clinical features, and provide clues for early treatment and early intervention.

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Prevalence of hepatitis B virus among chronic schizophrenia patients

Eastern Mediterranean Health Journal ◽

10.26719/2001.7.3.526 ◽

2001 ◽

Vol 7 (3) ◽

pp. 526-530

Author(s):

W. M. Said ◽

R. Saleh ◽

N. Jumaian

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Preventive Measures ◽

Risk Group ◽

Hepatitis B Surface Antigen ◽

Chronic Schizophrenia ◽

Healthy Controls ◽

B Virus ◽

The Difference ◽

Age And Sex

We aimed to determine the prevalence of hepatitis B surface antigen [HBsAg] among chronic schizophrenia patients in Jordan. Over a period of 12 months, 192 patients [106 male and 86 female] were tested for hepatitis B virus [HBV] by enzyme immunoassay. An equal number of age- and sex-matched healthy controls was also tested. Of the schizophrenia patients, 14 [10 male and 4 female] were positive for HBsAg while only 5 [4 male and 1 female] of the control subjects tested positive. The difference was not statistically significant but it indicates that chronic schizophrenia patients are a risk group for HBV infection and likely to benefit from preventive measures [health education and immunization against HBV].

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Cavernoma of the lateral ventricule presenting as speech arrests

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0038-1626205 ◽

2014 ◽

Vol 33 (01) ◽

pp. 82-84

Author(s):

Leonardo Conrado Silva Lima ◽

Marcelo Paglioli Ferreira ◽

Davidson Alba ◽

Alisson Roberto Teles ◽

Frederico Kliemann

Keyword(s):

Neurological Examination ◽

Brain Mri ◽

Cavernous Haemangioma ◽

Total Resection ◽

Cavernous Malformations ◽

Transcallosal Approach ◽

Vascular Channels ◽

Thin Walled ◽

Mri Study ◽

The Brain

AbstractCavernous malformations (CM) are formed by dilated thin-walled vascular channels without intervening parenchyma and intraventricular lesions are rare. We report a case of an intraventricular cavernoma in a 54-year old female patient. She presented with speech arrests daily for 10 months. Neurological examination revealed no deficits. The brain MRI study revealed an intraventricular lesion at the level of the left atrium, heterogeneously hyperintense on both T1 and T2-weighted images. It was performed an interhemispheric transcallosal approach with gross-total resection of the lesion. The histological examination was compatible with the diagnosis of cavernous haemangioma. In the postoperative period the patient presented with transient right hemiparesis with recovery in two weeks. We briefly review the literature concerning intraventricular cavernomas.

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Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001111 ◽

2021 ◽

Vol 9 (1) ◽

pp. e1111

Author(s):

Sandra Sif Gylfadottir ◽

Mustapha Itani ◽

Alexander Gramm Kristensen ◽

Hatice Tankisi ◽

Troels Staehelin Jensen ◽

...

Keyword(s):

Neuropathic Pain ◽

Diabetic Polyneuropathy ◽

Healthy Controls ◽

Cross Sectional ◽

Macrophage Density ◽

Calcitonin Gene ◽

Skin Biopsies ◽

Male Patients ◽

The Difference ◽

Age And Sex

Background and ObjectivesThe mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP).MethodsThe participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers.ResultsThere was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%, p < 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%, p < 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm−2 for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm−2 for SP and CGRP, respectively, p = 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm−2 for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes (p = 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients.DiscussionThe findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.

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Hemochromatosis mutations, dementia and brain iron deposition: a prospective cohort study

10.1101/2020.06.18.20134536 ◽

2020 ◽

Author(s):

David Melzer ◽

Janice L Atkins ◽

Luke C Pilling ◽

Christine J Heales ◽

Sharon Savage ◽

...

Keyword(s):

Iron Overload ◽

Gray Matter ◽

Brain Mri ◽

Iron Deposition ◽

European Ancestry ◽

Brain Iron ◽

Incident Dementia ◽

Gray Matter Volumes ◽

Brain Iron Deposition

ABSTRACTImportanceBrain iron deposition is common in dementia, but its causal significance is uncertain. The HFE p.C282Y homozygous mutation in European ancestry populations can lead to iron overload and hemochromatosis, mainly in males. Data on brain outcomes in homozygotes are scarce.ObjectiveTo estimate HFE variant associations with MRI features plus incident dementia diagnoses during follow-up in a large community based cohort.DesignUK Biobank cohort with follow-up in routine hospitalization records (mean 8.8 years). MRI imaging available on a participant subset scanned 2014 to 2018.SettingCommunity cohort participants across England, Wales and Scotland.ParticipantsEuropean ancestry participants (n=451,186) aged 40 to 70 years at baseline, including 2,890 p.C282Y homozygotes (predominantly without baseline haemochromatosis diagnoses). MRI scanning on 9,464 males and 10,475 females, including 40 male and 75 female p.C282Y homozygotes.ExposureHFE C282Y and H63D genetic variantsMain outcome and measuresBrain MRI site specific T2* measures (lower values associated with iron deposition) and gray matter volumes. Incident dementia diagnoses during follow-up.ResultsMale p.C282Y homozygotes had lower T2* measures in several brain areas including the thalamus (beta = -1.04 standard deviations, 95% CI -1.33 to -0.76, multiple testing adjusted p-value=4.9*10-10), putamen and hippocampus, compared to those without HFE mutations. Male homozygotes also had smaller gray matter volumes in the putamen (beta -0.80 sd, 95%CI -1.12 to - 0.47, adjusted p=2.2*10-4) and ventral striatum.Diagnoses of incident dementia (Hazard Ratio HR=2.27; 95% CI 1.36 to 3.80, p=0.002) were more common in p.C282Y homozygous men, as were delirium diagnoses (HR=2.04, CI 1.09 to 3.82, p=0.03), but there was no association with Stroke.In p.C282Y homozygote females and p.C282Y/H63D heterozygotes, MRI associations were less marked.Conclusion and RelevanceIn a community sample, men with the HFE p.C282Y homozygote genotype had more brain iron deposition, smaller specific gray matter volumes, and increased incidence of dementia. As iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.Key PointsQuestionIs the hemochromatosis HFE p.C282Y homozygous variant in men associated with brain MRI features and incident dementia?FindingsOn MRI, p.C282Y homozygote males had evidence of more iron deposition in areas including the thalamus, putamen and hippocampus, plus smaller putamen gray matter volumes, compared to men without HFE mutations. In 451,186 UK Biobank participants during the mean 8.8 year follow-up, incident dementia diagnoses were more than twice as common in the 1,294 homozygous men.MeaningAs iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.

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