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Björnfot, C., Eklund, A., Larsson, J., Hansson, W., Birnefeld, J., Garpebring, A., . . . Wåhlin, A. (2024). Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study. Journal of Cerebral Blood Flow and Metabolism
Open this publication in new window or tab >>Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study
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2024 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Article in journal (Refereed) Epub ahead of print
Abstract [en]

White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
4D flow MRI, cerebral small vessel disease, perivascular spaces, pulse wave velocity, white matter hyperintensities
National Category
Cardiac and Cardiovascular Systems Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-221120 (URN)10.1177/0271678X241230741 (DOI)001157963000001 ()38315044 (PubMedID)2-s2.0-85184419786 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RMX18-0152Swedish Heart Lung Foundation, 20180513Swedish Heart Lung Foundation, 20210653The Swedish Brain Foundation, F2022-0216Swedish Research Council, 2017-04949Swedish Research Council, 2022-04263Region Västerbotten
Available from: 2024-02-22 Created: 2024-02-22 Last updated: 2024-02-22
Birnefeld, J., Petersson, K., Wåhlin, A., Eklund, A., Birnefeld, E., Qvarlander, S., . . . Zarrinkoob, L. (2024). Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers . Anesthesiology, 140(4), 669-678
Open this publication in new window or tab >>Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers 
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2024 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 140, no 4, p. 669-678Article in journal (Refereed) Published
Abstract [en]

Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.

Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.

Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).

Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

Place, publisher, year, edition, pages
Wolters Kluwer, 2024
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-220047 (URN)10.1097/ALN.0000000000004775 (DOI)37756527 (PubMedID)2-s2.0-85187724522 (Scopus ID)
Funder
Region Västerbotten
Available from: 2024-01-26 Created: 2024-01-26 Last updated: 2024-04-08Bibliographically approved
Zarrinkoob, L., Myrnäs, S., Wåhlin, A., Eklund, A. & Malm, J. (2024). Cerebral blood flow patterns in patients with low-flow carotid artery stenosis, a 4D-PCMRI assessment. Journal of Magnetic Resonance Imaging
Open this publication in new window or tab >>Cerebral blood flow patterns in patients with low-flow carotid artery stenosis, a 4D-PCMRI assessment
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2024 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR).

Purpose: Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries.

Study Type: Prospective.

Subjects: Thirty-eight patients, age 72 ± 6 years (11 female).

Field Strength/Sequence: 3-Tesla, four-dimensional phase-contrast magnetic resonance imaging (4D-PCMRI).

Assessment: Patients with ischemic stroke or transient ischemic attack were evaluated regarding the degree of stenosis. 4D-PCMRI was used to measure cerebral BFR in 38 patients with symptomatic carotid stenosis (≥50%). BFR in the cerebral arteries was assessed in two subgroups based on symptomatic ICA-BFR: reduced ICA-flow (<160 mL/minutes) and preserved ICA-flow (≥160 mL/minutes). BFR laterality was defined as a difference in the paired ipsilateral-contralateral arteries.

Statistical Tests: Patients were grouped based on ICA-BFR (reduced vs. preserved). Statistical tests (independent sample t-test/paired t-test) were used to compare groups and hemispheres. Significance was determined at P < 0.05.

Results: The degree of stenosis was not significantly different, 80% (95% confidence interval [CI] = 73%–87%) in the reduced ICA-flow vs. 72% (CI = 66%–76%) in the preserved ICA-flow; P = 0.09. In the reduced ICA-flow group, a significantly reduced BFR was found in the ipsilateral middle cerebral artery and anterior cerebral artery (A1), while significantly increased in the contralateral A1. Retrograde BFR was found in the posterior communicating artery and ophthalmic artery. Significant BFR laterality was present in all paired arteries in the reduced ICA-flow group, contrasting the preserved ICA-flow group (P = 0.14–0.93).

Data Conclusions: 4D-PCMRI revealed compromised cerebral BFR due to carotid stenosis, not possible to detect by solely analyzing the degree of stenosis. In patients with reduced ICA-flow, collaterals were not sufficient to maintain symmetrical BFR distribution to the two hemispheres.

Evidence Level: 2.

Technical Efficacy: Stage 3.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
4D-PCMRI, cerebral blood flow, cerebrovascular disease, Circle of Willis, MRI, symptomatic carotid stenosis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-219323 (URN)10.1002/jmri.29216 (DOI)001135005100001 ()38168876 (PubMedID)2-s2.0-85181227868 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949Region VästerbottenSwedish Heart Lung Foundation, 20140592
Available from: 2024-01-15 Created: 2024-01-15 Last updated: 2024-01-15
Karalija, N., Papenberg, G., Johansson, J., Wåhlin, A., Salami, A., Andersson, M., . . . Nyberg, L. (2024). Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline. Neurobiology of Aging, 136, 125-132
Open this publication in new window or tab >>Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
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2024 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 136, p. 125-132Article in journal (Refereed) Published
Abstract [en]

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64–68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

Keywords
11C-raclopride, Aging, Dopamine D2-like receptor, Longitudinal, Magnetic resonance imaging, Positron emission tomography, Working memory
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-221540 (URN)10.1016/j.neurobiolaging.2024.02.001 (DOI)38359585 (PubMedID)2-s2.0-85185304249 (Scopus ID)
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Swedish Research Council, 2022-01804Umeå UniversityKnut and Alice Wallenberg Foundation, 2015.0277Jonas and Christina af Jochnick FoundationAlzheimerfonden, AF-967710Riksbankens Jubileumsfond, P20-0779Region Västerbotten
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
Holmgren, M., Henze, A., Wåhlin, A., Eklund, A., Fox, A. J. & Johansson, E. (2024). Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion. Neuroradiology, 66(4), 589-599
Open this publication in new window or tab >>Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion
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2024 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 66, no 4, p. 589-599Article in journal (Refereed) Published
Abstract [en]

Purpose: Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional ≥ 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion.

Methods: We included patients with ≥ 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI.

Results: We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional ≥ 50% stenoses (203 ml/min, P <.001). Definite use of ≥ 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P <.001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P =.78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P =.52), between near-occlusions and conventional ≥ 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions.

Conclusion: Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional ≥ 50% carotid stenosis.

Place, publisher, year, edition, pages
Springer Nature, 2024
Keywords
Carotid near-occlusion, Carotid stenosis, Collaterals, CT angiography, Intracerebral flow, Phase-contrast MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging Neurology
Identifiers
urn:nbn:se:umu:diva-221786 (URN)10.1007/s00234-024-03309-y (DOI)001169859900002 ()38400954 (PubMedID)2-s2.0-85185963642 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationRegion VästerbottenSwedish Heart Lung FoundationThe Swedish Stroke AssociationHarald Jeanssons stiftelseSwedish Society of Medicine
Available from: 2024-03-19 Created: 2024-03-19 Last updated: 2024-03-19Bibliographically approved
Holmgren, M., Henze, A., Wåhlin, A., Eklund, A., Fox, A. J. & Johansson, E. (2023). Diagnostic separation of conventional ⩾50% carotid stenosis and near-occlusion with phase-contrast MRI. European Stroke Journal
Open this publication in new window or tab >>Diagnostic separation of conventional ⩾50% carotid stenosis and near-occlusion with phase-contrast MRI
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2023 (English)In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881Article in journal (Refereed) Epub ahead of print
Abstract [en]

Introduction: The aim of this study was to assess sensitivity, specificity and interrater reliability of phase-contrast MRI (PC-MRI) for diagnosing carotid near-occlusion.

Patients and methods: Prospective cross-sectional study conducted between 2018 and 2021. We included participants with suspected 50%–100% carotid stenosis on at least one side, all were examined with CT angiography (CTA) and PC-MRI and both ICAs were analyzed. Degree of stenosis on CTA was the reference test. PC-MRI-based blood flow rates in extracranial ICA and intracranial cerebral arteries were assessed. ICA-cerebral blood flow (CBF) ratio was defined as ICA divided by sum of both ICAs and Basilar artery.

Results: We included 136 participants. The ICAs were 102 < 50% stenosis, 88 conventional ⩾50% stenosis (31 with ⩾70%), 49 near-occlusion, 12 occlusions, 20 unclear cause of small distal ICA on CTA and one excluded. For separation of near-occlusion and conventional stenoses, ICA flow rate and ICA-CBF ratio had the highest area under the curve (AUC; 0.98–0.99) for near-occlusion. ICA-CBF ratio ⩽0.225 was 90% (45/49) sensitive and 99% (188/190) specific for near-occlusion. Inter-rater reliability for this threshold was excellent (kappa 0.98). Specificity was 94% (29/31) for cases with ⩾70% stenosis. PC-MRI had modest performance for separating <50% and conventional ⩾50% stenosis (highest AUC 0.74), and eight (16%) of near-occlusions were not distinguishable from occlusion (no visible flow).

Conclusion: ICA-CBF ratio ⩽0.225 on PC-MRI is an accurate and reliable method to separate conventional ⩾50% stenosis and near-occlusion that is feasible for routine use. PC-MRI should be considered further as a potential standard method for near-occlusion detection, to be used side-by-side with established modalities as PC-MRI cannot separate other degrees of stenosis.

Place, publisher, year, edition, pages
Sage Publications, 2023
Keywords
Carotid stenosis, CT angiography, near-occlusion, phase-contrast MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-217715 (URN)10.1177/23969873231215634 (DOI)001112325800001 ()38032058 (PubMedID)2-s2.0-85178479481 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationRegion VästerbottenSwedish Heart Lung FoundationThe Swedish Stroke AssociationHarald and Greta Jeansson FoundationThe Swedish Medical AssociationUmeå University
Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2023-12-14
Wåhlin, A., Eklund, A. & Malm, J. (2022). 4D flow MRI hemodynamic biomarkers for cerebrovascular diseases. Journal of Internal Medicine, 291(2), 115-127
Open this publication in new window or tab >>4D flow MRI hemodynamic biomarkers for cerebrovascular diseases
2022 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 291, no 2, p. 115-127Article, review/survey (Refereed) Published
Abstract [en]

Alterations in cerebral blood flow are common in several neurological diseases among the elderly including stroke, cerebral small vessel disease, vascular dementia, and Alzheimer's disease. 4D flow magnetic resonance imaging (MRI) is a relatively new technique to investigate cerebrovascular disease, and makes it possible to obtain time-resolved blood flow measurements of the entire cerebral arterial venous vasculature and can be used to derive a repertoire of hemodynamic biomarkers indicative of cerebrovascular health.

The information that can be obtained from one single 4D flow MRI scan allows both the investigation of aberrant flow patterns at a focal location in the vasculature as well as estimations of brain-wide disturbances in blood flow. Such focal and global hemodynamic biomarkers show the potential of being sensitive to impending cerebrovascular disease and disease progression and can also become useful during planning and follow-up of interventions aiming to restore a normal cerebral circulation.

Here, we describe 4D flow MRI approaches for analyzing the cerebral vasculature. We then survey key hemodynamic biomarkers that can be reliably assessed using the technique. Finally, we highlight cerebrovascular diseases where one or multiple hemodynamic biomarkers are of central interest.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
Alzheimer's disease, atherosclerosis, carotid stenosis, cerebral blood flow, collateral circulation, phase-contrast MRI, small-vessel disease, stroke
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-190012 (URN)10.1111/joim.13392 (DOI)000722268700001 ()34813112 (PubMedID)2-s2.0-85119704251 (Scopus ID)
Available from: 2021-12-01 Created: 2021-12-01 Last updated: 2022-07-06Bibliographically approved
Vikner, T., Karalija, N., Eklund, A., Malm, J., Lundquist, A., Gallewicz, N., . . . Wåhlin, A. (2022). 5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions. Annals of Neurology, 92(5), 871-881
Open this publication in new window or tab >>5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions
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2022 (English)In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 92, no 5, p. 871-881Article in journal (Refereed) Published
Abstract [en]

Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD.

Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously.

Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI.

Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD. 

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-199208 (URN)10.1002/ana.26475 (DOI)000843724700001 ()36054261 (PubMedID)2-s2.0-85136905097 (Scopus ID)
Funder
Swedish Foundation for Strategic ResearchRegion Västerbotten, 2017‐04949Knut and Alice Wallenberg Foundation, 2017‐04949Max Planck SocietySwedish Research Council, 2017‐02217Swedish Research Council, 421‐2012‐648
Available from: 2022-09-08 Created: 2022-09-08 Last updated: 2023-05-04Bibliographically approved
Farnsworth von Cederwald, B., Josefsson, M., Wåhlin, A., Nyberg, L. & Karalija, N. (2022). Association of cardiovascular risk trajectory with cognitive decline and incident dementia. Neurology, 98(20), e2013-e2022
Open this publication in new window or tab >>Association of cardiovascular risk trajectory with cognitive decline and incident dementia
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2022 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 98, no 20, p. e2013-e2022Article in journal (Refereed) Published
Abstract [en]

Background and Objectives: Cardiovascular risk factors have a recently established association with cognitive decline and dementia, yet most studies examine this association through cross-sectional data, precluding an understanding of the longitudinal dynamics of such risk. The current study aims to explore how the ongoing trajectory of cardiovascular risk affects subsequent dementia and memory decline risk. We hypothesize that an accelerated, long-term accumulation of cardiovascular risk, as determined by the Framingham Risk Score (FRS), will be more detrimental to cognitive and dementia state outcomes than a stable cardiovascular risk.

Methods: We assessed an initially healthy, community-dwelling sample recruited from the prospective cohort Betula study. Cardiovascular disease risk, as assessed by the FRS, episodic memory performance, and dementia status were measured at each 5-year time point (T) across 20 to 25 years. Analysis was performed with bayesian additive regression tree, a semiparametric machine-learning method, applied herein as a multistate survival analysis method.

Results: Of the 1,244 participants, cardiovascular risk increased moderately over time in 60% of sample, with observations of an accelerated increase in 18% of individuals and minimal change in 22% of individuals. An accelerated, as opposed to a stable, cardiovascular risk trajectory predicted an increased risk of developing Alzheimer disease dementia (average risk ratio [RR] 3.3–5.7, 95% CI 2.6–17.5 at T2, 1.9–6.7 at T5) or vascular dementia (average RR 3.3–4.1, 95% CI 1.1–16.6 at T2, 1.5–7.6 at T5) and was associated with an increased risk of memory decline (average RR 1.4–1.2, 95% CI 1–1.9 at T2, 1–1.5 at T5). A stable cardiovascular risk trajectory appeared to partially mitigate Alzheimer disease dementia risk for APOE ε4 carriers.

Discussion: The findings of the current study show that the longitudinal, cumulative trajectory of cardiovascular risk is predictive of dementia risk and associated with the emergence of memory decline. As a result, clinical practice may benefit from directing interventions at individuals with accelerating cardiovascular risk.

Place, publisher, year, edition, pages
Wolters Kluwer, 2022
National Category
Psychology
Identifiers
urn:nbn:se:umu:diva-202461 (URN)10.1212/wnl.0000000000200255 (DOI)000796369700021 ()35444051 (PubMedID)2-s2.0-85130635509 (Scopus ID)
Funder
The Swedish Brain FoundationKnut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P17-0196:1
Available from: 2023-01-10 Created: 2023-01-10 Last updated: 2023-05-04Bibliographically approved
Nordin, K., Gorbach, T., Pedersen, R., Panes Lundmark, V., Johansson, J., Andersson, M., . . . Salami, A. (2022). DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging. Journal of Neuroscience Research, 100(6), 1296-1320
Open this publication in new window or tab >>DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging
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2022 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 100, no 6, p. 1296-1320Article in journal (Refereed) Published
Abstract [en]

Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age-related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5-year longitudinal study spanning the adult human lifespan. DyNAMiC examines age-related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age-sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age-related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u-shaped association between D1DR and resting-state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age-related cognitive decline.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
aging, cognition, connectome, dopamine, lifespan, PET
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-193314 (URN)10.1002/jnr.25039 (DOI)000769326800001 ()35293013 (PubMedID)2-s2.0-85126323267 (Scopus ID)
Funder
Swedish Research Council, 2016– 01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2022-03-29 Created: 2022-03-29 Last updated: 2023-04-25Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6784-1945

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