Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI

Frank J. Wolters, Hazel I. Zonneveld, Silvan Licher, Lotte G. M. Cremers, M. Kamran Ikram, Peter J. Koudstaal, Meike W. Vernooij, M. Arfan Ikram, Heart Brain Connection Collaborative Research Group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population. METHODS: Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion. RESULTS: During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%-62%) and 41% (15%-74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001). CONCLUSION: Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.
Original languageEnglish
Pages (from-to)e917-e926
JournalNeurology
Volume93
Issue number9
DOIs
Publication statusPublished - 27 Aug 2019

Cite this

Wolters, F. J., Zonneveld, H. I., Licher, S., Cremers, L. G. M., Ikram, M. K., Koudstaal, P. J., ... Heart Brain Connection Collaborative Research Group (2019). Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI. Neurology, 93(9), e917-e926. https://doi.org/10.1212/WNL.0000000000008003
Wolters, Frank J. ; Zonneveld, Hazel I. ; Licher, Silvan ; Cremers, Lotte G. M. ; Ikram, M. Kamran ; Koudstaal, Peter J. ; Vernooij, Meike W. ; Ikram, M. Arfan ; Heart Brain Connection Collaborative Research Group. / Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI. In: Neurology. 2019 ; Vol. 93, No. 9. pp. e917-e926.
@article{56d623cb710a48ffa88216f218522dac,
title = "Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI",
abstract = "OBJECTIVE: To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population. METHODS: Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7{\%} women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion. RESULTS: During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95{\%} confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1{\%}, and anemia was associated with a 34{\%} increased risk of dementia (95{\%} CI 11{\%}-62{\%}) and 41{\%} (15{\%}-74{\%}) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001). CONCLUSION: Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.",
author = "Wolters, {Frank J.} and Zonneveld, {Hazel I.} and Silvan Licher and Cremers, {Lotte G. M.} and Ikram, {M. Kamran} and Koudstaal, {Peter J.} and Vernooij, {Meike W.} and Ikram, {M. Arfan} and {Heart Brain Connection Collaborative Research Group}",
year = "2019",
month = "8",
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Wolters, FJ, Zonneveld, HI, Licher, S, Cremers, LGM, Ikram, MK, Koudstaal, PJ, Vernooij, MW, Ikram, MA & Heart Brain Connection Collaborative Research Group 2019, 'Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI' Neurology, vol. 93, no. 9, pp. e917-e926. https://doi.org/10.1212/WNL.0000000000008003

Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI. / Wolters, Frank J.; Zonneveld, Hazel I.; Licher, Silvan; Cremers, Lotte G. M.; Ikram, M. Kamran; Koudstaal, Peter J.; Vernooij, Meike W.; Ikram, M. Arfan; Heart Brain Connection Collaborative Research Group.

In: Neurology, Vol. 93, No. 9, 27.08.2019, p. e917-e926.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI

AU - Wolters, Frank J.

AU - Zonneveld, Hazel I.

AU - Licher, Silvan

AU - Cremers, Lotte G. M.

AU - Ikram, M. Kamran

AU - Koudstaal, Peter J.

AU - Vernooij, Meike W.

AU - Ikram, M. Arfan

AU - Heart Brain Connection Collaborative Research Group

PY - 2019/8/27

Y1 - 2019/8/27

N2 - OBJECTIVE: To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population. METHODS: Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion. RESULTS: During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%-62%) and 41% (15%-74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001). CONCLUSION: Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.

AB - OBJECTIVE: To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population. METHODS: Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion. RESULTS: During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%-62%) and 41% (15%-74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001). CONCLUSION: Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.

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DO - 10.1212/WNL.0000000000008003

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