Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls
by
, , ,
Ulf Jensen-Kondering
1,*
,
Veronique Kuhn
1,
Hannes Schacht
1,
Alexander Neumann
1,
Georg Royl
2 and
Peter Schramm
1 1
Department of Neuroradiology, UKSH Campus Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
2
Department of Neurology, UKSH Campus Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
*
Author to whom correspondence should be addressed.
Brain Sci. 2025, 15(8), 851; https://doi.org/10.3390/brainsci15080851
Submission received: 27 June 2025
/
Revised: 3 August 2025
/
Accepted: 7 August 2025
/
Published: 10 August 2025
(This article belongs to the Special Issue Cerebral Amyloid Angiopathy: Advances in the Field)
Abstract
Introduction: It has been recently demonstrated that some cerebral microbleeds (CMBs) are connected to cerebral veins in patients with cerebral small vessel disease (CSVD) including cerebral amyloid angiopathy (CAA). We sought to demonstrate the presence of CMB at 3 Tesla using susceptibility-weighted imaging and speculated that it was more prevalent in persons with Alzheimer’s disease (AD), another amyloid-related disease, than in healthy ageing controls. Material and Methods: We included persons from the publicly available OASIS3-database. Persons were included if they had a structural MRI including a susceptibility-weighted sequence (SWI) and relevant clinical data. Two raters assessed the presence and location of CMBs and CMBs with a venous connection (CMBven). Results: A total of 571 persons (AD, n = 140, healthy controls, n = 431) were included. In total, 367 CMBs were detected, encompassing 26/571 persons (4.5%) who had a total of 40/367 (10.9%) CMBs with a CMBven, though there was no difference between persons with AD and healthy controls (AD 6.6%, healthy controls 7.4%, p = 0.773). Persons with CMBven had a higher total CMB load, were more likely female, displayed an APOE ε2/2 genotype and had antithrombotic treatment more often. Logistic regression revealed a higher number of CMB (OR (95% CI) = 1.351 (1.161–1.688), p < 0.0014) and a lower MoCA score (OR (95% CI) = 0.862 (0.762–0.982), p = 0.018), indicating a statistically significant association with the presence of CMBven. Discussion: CMBven are not an uncommon finding in persons with AD and healthy ageing controls. Our results highlight the potential venous contribution to CSVD. Histopathological studies will be needed to assess these further.
1. Introduction
The contribution of small cerebral veins to cerebrovascular small vessel disease (CSVD) is known but underexplored [1]. Venous collagenosis may lead to vessel occlusion and stenosis [2]. Amyloid deposition, not only in leptomeningeal and cortical arteries but also veins [3,4], is the hallmark of cerebral amyloid angiopathy (CAA). It has been recently demonstrated that a subset of cerebral microbleeds (CMBs), a neuroimaging feature of CSVD and CAA in particular [5], has a connection to veins (CMBven) and may originate from the venous vasculature [6]. This demonstration was accomplished using high field strength (7 Tesla) and a dedicated imaging sequence and postprocessing algorithm (quantitative susceptibility mapping). The present study was conducted with two hypotheses, as follows: (1) The presence of CMBven can be demonstrated at a clinically available field strength (3 Tesla) and a widely available imaging sequence (susceptibility-weighted imaging, SWI) and (2) CMBven will be more prevalent in persons with Alzheimer’s disease (AD), another amyloid-driven pathology, than in healthy aging controls.
2. Materials and Methods
2.1. Database
Persons were included from the OASIS-3 database (https://sites.wustl.edu/oasisbrains/, last accessed 19 January 2024). The OASIS-3 database is a multimodal collection of clinical, laboratory and imaging data of >1000 participants accrued over the course of 15 years. It is managed by the Washington University Knight Alzheimer’s Disease Research Center and has been approved by the Institutional Review Board of Washington University School of Medicine. Persons gave their consent for the inclusion in the database and subsequent scientific use after anonymization [7]. Thus, the need to receive consent from individual persons was waived by the local ethics committee (Ethikkommision der Universität zu Lübeck, AZ 2024-403).
2.2. Participants
In a first instance, all persons with a diagnosis of AD according to the National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria and the presence of a 3 Tesla structural MRI including a susceptibility-weighted sequence (SWI) were included. Then, all available non-demented persons with the presence of a 3 Tesla structural MRI including a susceptibility-weighted sequence (SWI) who did not fulfill the diagnostic criteria for Alzheimer’s disease were included. Persons were excluded if an intracranial tumor, a macrohemorrhage or severe image degradation due to artifacts was present.
2.3. Image Acquisition and Interpretation
All imaging was performed on a 3 Tesla SIEMENS Trio (Siemens Medical Solutions USA, Inc., Malvern, PA, USA) with a head coil and whole brain coverage. Sequence parameters were the following: TE = 200 ms, TR = 280 ms, flip angle = 15°, and slice thickness = 2 mm.
Two raters (UJK, board certified neuroradiologist with 15 years of experience, and VK, junior doctor with 1 year of experience) rated the number and presence of CMB according to the STRIVE criteria. For the purpose of this study CMBs in the frontal, parietal, temporal, occipital and insular lobes were categorized as lobar CMBs while basal ganglia, thalami and brain stem were categorized as deep CMBs. Cerebellar CMBs were counted as a separate region [8]. Mixed CMBs were defined as the presence of at least one CMB in a lobar and a deep region each.
A venous connection was rated as present if a venous vessel was detected in the direct vicinity, with no brain parenchyma between the vessel and the CMB. If there was disagreement, the rating of the first rater was used.
2.4. Clinical Parameters
Age, sex, race, apolipoprotein ε (APOE) genotype, arterial hypertension, a history of stroke or TIA, diabetes, hypercholesterinemia, antithrombotic treatment (any thrombocyte aggregation inhibitor or anticoagulation) and Montreal Cognitive Assessment (MoCA) score was recorded.
2.5. Statistics
R (version 4.4.1, R Foundation for Statistical Computing, Vienna, Austria) was used for statistical calculations. Mean, standard deviation, median, ranges and proportions are displayed for the variables as appropriate. Comparisons between groups were made with a t-test for normally distributed continuous variables, Mann–Whitney U test for non-normally distributed or ordinal scale variables, or a Chi-square test or Fisher’s exact test as appropriate for categorical variables. Interrater agreement was calculated using the intraclass correlation coefficient (ICC) for the total number of CMBs, while, for the assessment of the presence of CMBven, Cohens’s κ was calculated. The total number of CMBs, gender, APOE genotype, MoCA score, age and antithrombotic therapy were included as variables in a logistic regression model. A Hosmer–Lemeshow test for the calculation of the goodness of fit of the model was performed. All tests were two sided and a p-value of <0.05 was considered statistically significant.
3. Results
3.1. Entire Cohort
A total of 571 persons could be included. Of these, 140 were judged to have AD, whereas 431 did not. Mean age was 69.3 ± 9.2 years, 59.4% (n = 339) were female and the majority (85.3%, n = 487) was white. Approximately half of the persons had a history of hypertension (45.5%) and hypercholesterinemia (46.1%) and were on antithrombotic treatment (50.9%). A minority of the persons had a history of TIA or stroke (4.4%) or diabetes (9.6%). Median MoCA score was 26 (interquartile range 23–28), Table 1.
3.2. Cerebral Microbleeds
A total of 367 CMBs in 116 individual persons were identified. ICC for the number of total CMBs was 0.98. The median number of CMBs per person was 0 with a range of 0 to 28. Most were located in lobar regions (75.5%), followed by deep (13.1%) and cerebellar (10.9%). A total of 15 persons had mixed CMBs.
3.3. AD vs. Healthy Controls
Persons in the AD group were significantly older (77 ± 6.7 vs. 67 ± 8.7 years, p < 0.001), less often female (49.3 vs. 62.6%, p = 0.004), displayed an APOE ε3/3 genotype more often (42.9 vs. 54.8%, p = 0.012) had a lower median MoCA score (21 vs. 27, p < 0.001), and were on antithrombotic treatment more often (64 vs. 47%, p < 0.001).
Persons in the AD group had less total CMBs per person (median 0, range 0–22 vs. 0, range 0–28, p = 0.034), more total deep CMBs (21.9 vs. 6.9%, p < 0.001), more deep CMBs per person (median 0, range 0–6 vs. 0, range 0–3, p < 0.001), a lower number of lobar CMBs (68.2 vs. 80.5%, p = 0.006), a lower number of cerebellar CMBs per person (median 0, range 0–3 vs. 0, range 0–13, p = 0.029) and a greater share of persons with mixed CMBs (6.4 vs. 1.4%, p = 0.001), Table 1.
3.4. Cerebral Microbleeds with a Venous Connection
The total number of CMBven was 40 in 26 individual persons. Cohen’s κ for the presence of CMBven was 0.77. Most were located in lobar regions (93%), followed by deep (5%) and cerebellar (2%), Figure 1, Table 2.
Persons with CMBven were less often female (35 vs. 59.4%, p < 0.001); displayed an APOE ε 2/2 more frequently, although absolute numbers were very small (3.8 vs. 0.55%, n = 1 vs. n = 2, p = 0.016); were on antithrombotic treatment more often (73 vs. 50.2%, p = 0.005); had a lower median MoCA score (24 vs. 26, p = 0.014); and had more CMBs per person (median 3.5 vs. 0, p < 0.001), as shown in Table 3.
Only a higher number of CMB (OR (95% CI) = 1.351 (1.161–1.688), p < 0.0014) and a lower MoCA score (OR (95% CI) = 0.862 (0.762–0.982), p = 0.018) showed a statistically significant association with the presence of CMBven (Table 4). Goodness-of-fit calculation indicated a good model fit with χ2 = 8.467, p = 0.389.
4. Discussion
We have demonstrated that approximately 10% of the CMB found in patients with AD and healthy aging controls have a connection to cerebral veins on 3 Tesla using SWI, i.e., at a clinically available field strength and with a routinely employed MRI sequence. This number is in agreement with the results by Rotta and coworkers who demonstrated a connection of CMBs to small cerebral veins on QSM at 7 Tesla in patients with CSVD (CAA and hypertensive arteriopathy) and healthy controls in 14% of all CMBs [6]. In contrast to their work, we could not demonstrate a difference between persons with AD and healthy controls. A connection of CMBs with small cerebral veins has been previously described by Ayaz and coworkers in SWI at 1.5 Tesla in patients with mild cognitive impairment [9] as an adjunct finding. Their frequency however was not reported. A single case report of a patient with CAA-related inflammation also found most CMBs with a venous connection using SWI, though at a clinically unusual field strength (5 Tesla) [10].
It is widely accepted that amyloid plays a key role in the development of AD. Parenchymal amyloid depositions induce tau aggregations that lead to neuronal death and the typical clinical dementia [11]. While Aβ40 is the key player in CAA, Aβ42 is preferentially deposited in AD [12]. It is increasingly recognized that CAA and AD demonstrate a pathological overlap. This is exemplified by the fact that up to 80% of patients with AD exhibit neuropathological features of CAA [13]. Further, 30% of patients have CMBs [14].
Only a few studies have been dedicated to the contribution of veins to CSVD, a topic vastly underexplored compared with arteries. Collagenosis of small veins leads to wall thickening, stenosis and occlusion of small cerebral veins which may contribute to periventricular white matter lesions in patients with AD [2,15]. It is postulated that venous collagenosis [15] and venous Aβ deposition [16] impairs venous resistance and pulsatility [17], altering cerebral blood flow autoregulation [18] and reduces efflux of interstitial fluid, in turn impeding Aβ clearance and facilitating Aβ deposition [19]. In our study, the number of total CMBs and a lower MoCA score was associated with the presence of CMBven. This could indicate that more severe tissue damage and advanced Aβ deposition could lead to more pronounced venous pathology.
In a mouse model, infarcts due to the occlusion of cortical venules were strikingly similar to infarcts due to the occlusion of arterioles [20]. However, several studies were unable to find a relationship between enlarged perivascular spaces and veins [21,22,23].
We cannot exclude the idea that these CMB constitute venous aneurysms [24] or that the assumed connection is indeed caused by mere spatial proximity and blooming artifacts [25] feigning an actual connection. Moreover, even if there is a contact point between CMB and a vein this association could still be by random and the CMB arterial. Further, additional features such as recently discovered blood-based biomarkers and other non-standard markers are not included in the OASIS-database and cannot be taken into account as a potential influence on the presence of CMBven. Histopathological studies dedicated to the question of whether these CMBs are of arterial or venous origin, a subject that has been previously neglected [26], will shed light on this question.
5. Conclusions
CMB with a venous connection are not an uncommon finding. Our results put a focus on the potential venous side of CMBs and the contribution of veins in CSVD in general and amyloid-driven disease in particular. Histopathological studies will be needed to elucidate that relationship.
Author Contributions
Conceptualization, U.J.-K. and V.K.; methodology, U.J.-K.; formal analysis, U.J.-K. and V.K.; investigation, U.J.-K. and V.K.; resources, G.R. and P.S.; data curation, U.J.-K.; writing—original draft preparation, U.J.-K.; writing—review and editing, U.J.-K., V.K., H.S., A.N., G.R., P.S.; visualization, U.J.-K.; supervision, U.J.-K., G.R. and P.S.; H.S., A.N., G.R. and U.J.-K., project administration. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The OASIS-3 database was approved by the Institutional Review Board of Washington University School of Medicine. This study was approved by the local ethics committee (Ethikkommision der Universität zu Lübeck, AZ 2024-403).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study for data acquisition and subsequent analysis of anonymized data.
Data Availability Statement
Data are contained within the article. These data were derived from the following resources available in the public domain: https://sites.wustl.edu/oasisbrains/, https://sites.wustl.edu/oasisbrains/ last accessed 19 January 2024. Further material is available from the corresponding author upon reasonable request.
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
The following abbreviations are used in this manuscript:
| AD | Alzheimer’s disease |
| APOE | Apoliptoprotein E |
| CAA | Cerebral amyloid angiopathy |
| CMB | Cerebral microbleed |
| CMBven | Cerebral microbleeds with a venous connection |
| CVSD | Cerebrovascular small vessel disease |
| MoCA | Montreal cognitive assessment |
| SWI | Susceptibility-weighted imaging |
References
- Zedde, M.; Grisendi, I.; Assenza, F.; Vandelli, G.; Napoli, M.; Moratti, C.; Lochner, P.; Seiffge, D.J.; Piazza, F.; Valzania, F.; et al. The Venular Side of Cerebral Amyloid Angiopathy: Proof of Concept of a Neglected Issue. Biomedicines 2023, 11, 2663. [Google Scholar] [CrossRef] [PubMed]
- Keith, J.; Gao, F.; Noor, R.; Kiss, A.; Balasubramaniam, G.; Au, K.; Rogaeva, E.; Masellis, M.; Black, S.E. Collagenosis of the Deep Medullary Veins: An Underrecognized Pathologic Correlate of White Matter Hyperintensities and Periventricular Infarction? J. Neuropathol. Exp. Neurol. 2017, 76, 299–312. [Google Scholar] [CrossRef]
- Charidimou, A.; Boulouis, G.; Gurol, M.E.; Ayata, C.; Bacskai, B.J.; Frosch, M.P.; Viswanathan, A.; Greenberg, S.M. Emerging Concepts in Sporadic Cerebral Amyloid Angiopathy. Brain 2017, 140, 1829–1850. [Google Scholar] [CrossRef]
- Mendel, T.; Wierzba-Bobrowicz, T.; Stępień, T.; Szpak, G.M. Original Article β-Amyloid Deposits in Veins in Patients with Cerebral Amyloid Angiopathy and Intracerebral Haemorrhage. Folia Neuropathol. 2013, 2, 120–126. [Google Scholar] [CrossRef]
- Charidimou, A.; Boulouis, G.; Frosch, M.P.; Baron, J.-C.; Pasi, M.; Albucher, J.F.; Banerjee, G.; Barbato, C.; Bonneville, F.; Brandner, S.; et al. The Boston Criteria Version 2.0 for Cerebral Amyloid Angiopathy: A Multicentre, Retrospective, MRI–Neuropathology Diagnostic Accuracy Study. Lancet Neurol. 2022, 21, 714–725. [Google Scholar] [CrossRef]
- Rotta, J.; Perosa, V.; Yakupov, R.; Kuijf, H.J.; Schreiber, F.; Dobisch, L.; Oltmer, J.; Assmann, A.; Speck, O.; Heinze, H.-J.; et al. Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI. Neurology 2021, 96, E2048–E2057. [Google Scholar] [CrossRef] [PubMed]
- LaMontagne, P.J.; Benzinger, T.L.S.; Morris, J.C.; Keefe, S.; Hornbeck, R.; Xiong, C.; Grant, E.; Hassenstab, J.; Moulder, K.; Vlassenko, A.G.; et al. OASIS-3: Longitudinal Neuroimaging, Clinical, and Cognitive Dataset for Normal Aging and Alzheimer Disease. 2019. Available online: https://www.medrxiv.org/content/10.1101/2019.12.13.19014902v1 (accessed on 6 August 2025).
- Gregoire, S.M.; Chaudhary, U.J.; Brown, M.M.; Yousry, T.A.; Kallis, C.; Jäger, H.R.; Werring, D.J. The Microbleed Anatomical Rating Scale (MARS). Neurology 2009, 73, 1759–1766. [Google Scholar] [CrossRef]
- Ayaz, M.; Boikov, A.; McAuley, G.; Schrag, M.; Kido, D.K.; Haacke, E.M.; Kirsch, W. Imaging Cerebral Microbleeds with SWI. In Susceptibility Weighted Imaging in MRI. Basic Concepts and Clinical Applications; Haacke, E.M., Reichenbach, J.R., Eds.; Wiley-Blackwell: Hoboken, NJ, USA, 2011; pp. 191–214. [Google Scholar]
- Wang, Y.; Fan, X.; Ni, J.; Feng, F. Dilated Juxtacortical Perivascular Spaces and Venous Cerebral Microbleeds in Cerebral Amyloid Angiopathy-Related Inflammation. Ann. Neurol. 2023, 94, 605–607. [Google Scholar] [CrossRef]
- Kepp, K.P.; Robakis, N.K.; Høilund-Carlsen, P.F.; Sensi, S.L.; Vissel, B. The Amyloid Cascade Hypothesis: An Updated Critical Review. Brain 2023, 146, 3969–3990. [Google Scholar] [CrossRef]
- Greenberg, S.M.; Bacskai, B.J.; Hernandez-Guillamon, M.; Pruzin, J.; Sperling, R.; van Veluw, S.J. Cerebral Amyloid Angiopathy and Alzheimer Disease—One Peptide, Two Pathways. Nat. Rev. Neurol. 2020, 16, 30–42. [Google Scholar] [CrossRef] [PubMed]
- Thal, D.R.; Griffin, W.S.T.; de Vos, R.A.I.; Ghebremedhin, E. Cerebral Amyloid Angiopathy and Its Relationship to Alzheimer’s Disease. Acta Neuropathol. 2008, 115, 599–609. [Google Scholar] [CrossRef]
- Cordonnier, C.; van der Flier, W.M. Brain Microbleeds and Alzheimer’s Disease: Innocent Observation or Key Player? Brain 2011, 134, 335–344. [Google Scholar] [CrossRef] [PubMed]
- Moody, D.M.; Brown, W.R.; Challa, V.R.; Anderson, R.L. Periventricular Venous Collagenosis: Association with Leukoaraiosis. Radiology 1995, 194, 469–476. [Google Scholar] [CrossRef] [PubMed]
- Weller, R.O.; Massey, A.; Newman, T.A.; Hutchings, M.; Kuo, Y.-M.; Roher, A.E. Cerebral Amyloid Angiopathy. Am. J. Pathol. 1998, 153, 725–733. [Google Scholar] [CrossRef]
- Black, S.; Gao, F.; Bilbao, J. Understanding White Matter Disease. Stroke 2009, 40, S48–S52. [Google Scholar] [CrossRef] [PubMed]
- Kalaria, R.N. Linking Cerebrovascular Defense Mechanisms in Brain Ageing and Alzheimer’s Disease. Neurobiol. Aging 2009, 30, 1512–1514. [Google Scholar] [CrossRef]
- Morrone, C.D.; Bishay, J.; McLaurin, J. Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis. Int. J. Mol. Sci. 2020, 21, 1985. [Google Scholar] [CrossRef]
- Shih, A.Y.; Blinder, P.; Tsai, P.S.; Friedman, B.; Stanley, G.; Lyden, P.D.; Kleinfeld, D. The Smallest Stroke: Occlusion of One Penetrating Vessel Leads to Infarction and a Cognitive Deficit. Nat. Neurosci. 2013, 16, 55–63. [Google Scholar] [CrossRef]
- Bouvy, W.H.; Kuijf, H.J.; Zwanenburg, J.J.M.; Koek, H.L.; Kappelle, L.J.; Luijten, P.R.; Ikram, M.K.; Biessels, G.J. Abnormalities of Cerebral Deep Medullary Veins on 7 Tesla MRI in Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease: A Pilot Study. J. Alzheimer’s Dis. 2017, 57, 705–710. [Google Scholar] [CrossRef]
- Jochems, A.C.C.; Blair, G.W.; Stringer, M.S.; Thrippleton, M.J.; Clancy, U.; Chappell, F.M.; Brown, R.; Jaime Garcia, D.; Hamilton, O.K.L.; Morgan, A.G.; et al. Relationship Between Venules and Perivascular Spaces in Sporadic Small Vessel Diseases. Stroke 2020, 51, 1503–1506. [Google Scholar] [CrossRef]
- Okudera, T.; Huang, Y.P.; Fukusumi, A.; Nakamura, Y.; Hatazawa, J.; Uemura, K. Micro-Angiographical Studies of the Medullary Venous System of the Cerebral Hemisphere. Neuropathology 1999, 19, 93–111. [Google Scholar] [CrossRef] [PubMed]
- van Veluw, S.J.; Charidimou, A.; van der Kouwe, A.J.; Lauer, A.; Reijmer, Y.D.; Costantino, I.; Gurol, M.E.; Biessels, G.J.; Frosch, M.P.; Viswanathan, A.; et al. Microbleed and Microinfarct Detection in Amyloid Angiopathy: A High-Resolution MRI-Histopathology Study. Brain 2016, 139, 3151–3162. [Google Scholar] [CrossRef]
- Wang, Y.; Liu, T. Quantitative Susceptibility Mapping (QSM): Decoding MRI Data for a Tissue Magnetic Biomarker. Magn. Reson. Med. 2015, 73, 82–101. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.; Wardlaw, J.M. Update on Cerebral Small Vessel Disease: A Dynamic Whole-Brain Disease. Stroke Vasc. Neurol. 2016, 1, 83–92. [Google Scholar] [CrossRef] [PubMed]
Figure 1.
Examples of CMBs with a connection to veins (arrowheads) in the cortex (A,B), in the thalamus (C) and in the brain stem (D).
Figure 1.
Examples of CMBs with a connection to veins (arrowheads) in the cortex (A,B), in the thalamus (C) and in the brain stem (D).
Table 1.
Demographics of the participants.
| Total (n = 571) | AD (n = 140) | No AD (n = 431) | p-Value | |
|---|---|---|---|---|
| Age, mean ± SD | 69.3 ± 9.2 | 77 ± 6.7 years | 67 ± 8.7 years | <0.001 # |
| Female sex, n (%) | 339 (59.4) | 69 (49.3) | 270 (62.6) | 0.004 § |
| Race | ||||
| Asian, n (%) | 3 (0.5) | 0 (0) | 3 (0.7) | 1 * |
| Black, n (%) | 80 (14) | 14 (10) | 66 (15.3) | 0.11 § |
| White, n (%) | 487 (85.3) | 126 (90) | 361 (83.8) | 0.094 § |
| APOE | ||||
| ε2/2, n (%) | 3 (0.5) | 1 (0.7) | 2 (0.46) | 0.732 § |
| ε2/3, n (%) | 66 (11.5) | 13 (9.3) | 53 12.3) | 0.324 § |
| ε2/4, n (%) | 12 (2.1) | 1 (0.7) | 11 (2.6) | 0.185 § |
| ε3/3, n (%) | 296 (51.8) | 60 (42.9) | 236 (54.8) | 0.012 § |
| ε3/4, n (%) | 166 (29) | 56 (40) | 110 (25.5) | 0.001 § |
| ε4/4, n (%) | 25 (4.4) | 8 (5.7) | 17 (3.9) | 0.380 § |
| History of stroke/TIA, n (%) | 25 (4.4) | 10 (7.1) | 15 (3.5) | 0.065 § |
| Arterial hypertension, n (%) | 260 (45.5) | 73 (52.1) | 187 (43.4) | 0.07 § |
| Diabetes, n (%) | 55 (9.6) | 15 (10.7) | 40 (9.3) | 0.61 § |
| Hypercholesterinemia, n (%) | 263 (46.1) | 66 (47.1) | 197 (45.7) | 0.767 § |
| Antithrombotic treatment, n (%) | 291 (50.9) | 90 (64) | 201 (47) | <0.001 § |
| MoCA, median (IQR), range | 26 (23, 28), 7–30 | 21 (17.5, 24), 7–30 | 27 (25, 28), 15–30 | <0.001 $ |
AD: Alzheimer’s disease; SD: Standard deviation; APOE: Apolipoprotein; TIA: Transient ischemic attack; MoCA: Montreal cognitive assessment; IQR: Interquartile range. #: t-test; §: χ2-test; *: Fisher’s exact test; $: Mann–Whitney U test.
Table 2.
Results for the cerebral microbleeds (CMBs).
| Total (n = 571) | AD (n = 140) | No AD (n = 431) | p-Value | |
|---|---|---|---|---|
| Persons with any CMB, n (%) | 116 (20.3) | 36 (25.7) | 80 (18.6) | 0.067 § |
| Total CMB, n | 367 | 151 | 216 | NA |
| CMB per person, median (IQR), range | 0 (0, 0), 0–28 | 0 (0, 1), 0–22 | 0 (0, 0), 0–28 | 0.034 $ |
| Deep CMB total, n (%) | 48 (13.1) | 33 (21.9) | 15 (6.9) | <0.001 § |
| Deep CMB per person, median (IQR), range | 0 (0, 0), 0–6 | 0 (0, 0), 0–6 | 0 (0, 0), 0–3 | <0.001 $ |
| Lobar CMB total, n (%) | 277 (75.5) | 103 (68.2) | 174 (80.5) | 0.006 § |
| Lobar CMB per person, median (IQR), range | 0 (0, 0), 0–28 | 0 (0, 0), 0–16 | 0 (0, 0), 0–28 | 0.124 $ |
| Persons with mixed CMB, n (%) | 15 (2.6) | 9 (6.4) | 6 (1.4) | 0.001 § |
| Cerebellar CMB total, n (%) | 40 (10.9) | 15 (9.9) | 25 (11.6) | 0.084 § |
| Cerebellar CMB per person, median (IQR), range | 0 (0, 0), 0–13 | 0 (0, 0), 0–3 | 0 (0, 0), 0–13 | 0.029 $ |
| Persons with any CMBven, n (%) | 26 (4.5) | 10 (6.6) | 16 (7.4) | 0.773 § |
| Total CMBven, n (%) | 40 (10.9) | 12 (7.9) | 28 (12.9) | 0.403 § |
| Deep CMBven, n (%) | 2 (0.5) | 2 (1.3) | 0 (0) | 0.059 * |
| Deep CMBven per person, median (IQR), range | 0 (0, 0), 0–1 | 0 (0, 0), 0–1 | 0 (0, 0), 0 | 0.013 $ |
| Lobar CMBven, n (%) | 37 (10.1) | 10 (6.6) | 27 (12.5) | 0.713 § |
| Lobar CMBven per person, median (IQR), range | 0 (0, 0), 0–4 | 0 (0, 0), 0–2 | 0 (0, 0), 0–4 | 0.181 $ |
| Cerebellar CMBven, n (%) | 1 (0.3) | 0 (0) | 1 (0.5) | 1 * |
| Cerebellar CMBven per person, median (IQR), range | 0 (0, 0), 0–1 | 0 (0, 0), 0 | 0 (0, 0), 0–1 | 0.571 $ |
AD: Alzheimer’s disease; IQR: Interquartile range. §: χ2-test; *: Fisher’s exact test; $: Mann–Whitney U test, NA: not applicable.
Table 3.
Results for the cerebral microbleeds (CMBs) with and without a venous connection.
| CMBven Present (n = 26) | CMBven Absent (n = 545) | p-Value | |
|---|---|---|---|
| Age, mean ± SD | 72.3 ± 8.8 years | 68.9 ± 9.2 | 0.069 # |
| Female sex, n (%) | 9 (35) | 324 (59.4) | <0.001 § |
| Race | |||
| Asian, n (%) | 0 (0) | 3 (0.5) | 1 * |
| Black, n (%) | 2 (7.7) | 76 (13.9) | 0.364 § |
| White, n (%) | 24 (92.3) | 465 (85.3) | 0.320 § |
| APOE | |||
| ε2/2, n (%) | 1 (3.8) | 2 (0.55) | 0.016 § |
| ε2/3, n (%) | 2 (7.7) | 63 (11.6) | 0.544 § |
| ε2/4, n (%) | 0 (0) | 12 (2.2) | 1 * |
| ε3/3, n (%) | 16 (62) | 288 (52.8) | 0.385 § |
| ε3/4, n (%) | 5 (19.2) | 153 (28) | 0.324 § |
| ε4/4, n (%) | 2 (7.7) | 24 (4.4) | 0.431 § |
| History of stroke/TIA, n (%) | 2 (7.7) | 23 (4.2) | 0.397 § |
| Arterial hypertension, n (%) | 10 (38.4) | 248 (45.5) | 0.480 § |
| Diabetes, n (%) | 3 (11.5) | 52 (9.5) | 0.735 § |
| Hypercholesterinemia, n (%) | 9 (34.6) | 248 (45.5) | 0.275 § |
| Antithrombotic treatment, n (%) | 19 (73) | 274 (50.2) | 0.005 § |
| MoCA, median (IQR), range | 24 (20, 25.75), 8–28 | 26 (24, 28), 7–30 | 0.014 $ |
| CMB per person, median (IQR), range | 3.5 (2, 5), 1–28 | 0 (0, 0), 0–21 | <0.001 $ |
AD: Alzheimer’s disease; SD: Standard deviation; APOE: Apolipoprotein; TIA: Transient ischemic attack; MoCA: Montreal cognitive assessment; IQR: Interquartile range. #: t-test; §: χ2-test; *: Fisher’s exact test; $: Mann–Whitney U test.
Table 4.
Logistic regression analysis of factors associated with the presence of CMBven. Odds ratios (OR), 95% confidence intervals (CI) and p-values are reported. * indicates statistical significance (p < 0.05).
Table 4.
Logistic regression analysis of factors associated with the presence of CMBven. Odds ratios (OR), 95% confidence intervals (CI) and p-values are reported. * indicates statistical significance (p < 0.05).
| Variable | OR (95% CI) | p-Value |
|---|---|---|
| Total CMB number | 1.351 (1.161–1.688) | <0.0014 * |
| Gender | 1.427 (0.392–5.419) | 0.585 |
| APOE ε genotype | 1.558 (0.002–92.812) | 0.874 |
| MoCA score | 0.862 (0.762–0.982) | 0.018 * |
| Age | 0.968 (0.899–1.045) | 0.397 |
| Antithrombotic treatment | 0.916 (0.246–3.470) | 0.894 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Jensen-Kondering, U.; Kuhn, V.; Schacht, H.; Neumann, A.; Royl, G.; Schramm, P. Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls. Brain Sci. 2025, 15, 851. https://doi.org/10.3390/brainsci15080851
AMA Style
Jensen-Kondering U, Kuhn V, Schacht H, Neumann A, Royl G, Schramm P. Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls. Brain Sciences. 2025; 15(8):851. https://doi.org/10.3390/brainsci15080851
Chicago/Turabian StyleJensen-Kondering, Ulf, Veronique Kuhn, Hannes Schacht, Alexander Neumann, Georg Royl, and Peter Schramm. 2025. "Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls" Brain Sciences 15, no. 8: 851. https://doi.org/10.3390/brainsci15080851
APA StyleJensen-Kondering, U., Kuhn, V., Schacht, H., Neumann, A., Royl, G., & Schramm, P. (2025). Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls. Brain Sciences, 15(8), 851. https://doi.org/10.3390/brainsci15080851
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
