The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation
Abstract Background Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral...
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BMC
2025-01-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-024-01652-z |
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| author | Mark Bitsch Vestergaard Aftab Bakhtiari Merete Osler Erik Lykke Mortensen Ulrich Lindberg Ian Law Martin Lauritzen Krisztina Benedek Henrik Bo Wiberg Larsson |
| author_facet | Mark Bitsch Vestergaard Aftab Bakhtiari Merete Osler Erik Lykke Mortensen Ulrich Lindberg Ian Law Martin Lauritzen Krisztina Benedek Henrik Bo Wiberg Larsson |
| author_sort | Mark Bitsch Vestergaard |
| collection | DOAJ |
| description | Abstract Background Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (ΔCBFVis.Act.) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort. Methods 64 subjects participated in the present study. ΔCBFVis.Act. was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI. Results ΔCBFVis.Act. correlated negatively ( $$\beta$$ β = -32.1 [95% confidence interval (CI): -60.2; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. ΔCBFVis.Act. did not correlate with FDG SUVr ( $$\beta$$ β = 1.9 [CI: -23.8; 27.6], r = 0.02, p = 0.88) or cortical thickness ( $$\beta$$ β = 10.3 [CI: -8.4; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation ( $$\beta$$ β = -17.8 [CI:-71.9; 36.2], r =- 0.09, p = 0.51) nor in the remaining cortex ( $$\beta$$ β = 5.2 [CI:-3.9; 14.2], r = 0.15, p = 0.26). Conclusion We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease. |
| format | Article |
| id | doaj-art-5c25e33d833b468ea9a8ce3dd799e07e |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-5c25e33d833b468ea9a8ce3dd799e07e2025-01-05T12:10:40ZengBMCAlzheimer’s Research & Therapy1758-91932025-01-0117111210.1186/s13195-024-01652-zThe cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulationMark Bitsch Vestergaard0Aftab Bakhtiari1Merete Osler2Erik Lykke Mortensen3Ulrich Lindberg4Ian Law5Martin Lauritzen6Krisztina Benedek7Henrik Bo Wiberg Larsson8Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital RigshospitaletFunctional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital RigshospitaletCenter for Clinical Research and Prevention, Copenhagen University Hospital Bispebjerg and FrederiksbergDepartment of Public Health, University of CopenhagenFunctional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital RigshospitaletDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital RigshospitaletDepartment of Clinical Neurophysiology, Copenhagen University Hospital RigshospitaletDepartment of Clinical Neurophysiology, Copenhagen University Hospital RigshospitaletFunctional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital RigshospitaletAbstract Background Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (ΔCBFVis.Act.) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort. Methods 64 subjects participated in the present study. ΔCBFVis.Act. was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI. Results ΔCBFVis.Act. correlated negatively ( $$\beta$$ β = -32.1 [95% confidence interval (CI): -60.2; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. ΔCBFVis.Act. did not correlate with FDG SUVr ( $$\beta$$ β = 1.9 [CI: -23.8; 27.6], r = 0.02, p = 0.88) or cortical thickness ( $$\beta$$ β = 10.3 [CI: -8.4; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation ( $$\beta$$ β = -17.8 [CI:-71.9; 36.2], r =- 0.09, p = 0.51) nor in the remaining cortex ( $$\beta$$ β = 5.2 [CI:-3.9; 14.2], r = 0.15, p = 0.26). Conclusion We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease.https://doi.org/10.1186/s13195-024-01652-zβ-amyloidCerebral blood flowCerebrovascular functionCerebrovascular reactivityNeurovascular couplingAging |
| spellingShingle | Mark Bitsch Vestergaard Aftab Bakhtiari Merete Osler Erik Lykke Mortensen Ulrich Lindberg Ian Law Martin Lauritzen Krisztina Benedek Henrik Bo Wiberg Larsson The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation Alzheimer’s Research & Therapy β-amyloid Cerebral blood flow Cerebrovascular function Cerebrovascular reactivity Neurovascular coupling Aging |
| title | The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation |
| title_full | The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation |
| title_fullStr | The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation |
| title_full_unstemmed | The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation |
| title_short | The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation |
| title_sort | cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β amyloid accumulation |
| topic | β-amyloid Cerebral blood flow Cerebrovascular function Cerebrovascular reactivity Neurovascular coupling Aging |
| url | https://doi.org/10.1186/s13195-024-01652-z |
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