Utility of Cerebrovascular Imaging Biomarkers to Detect Cerebral Amyloidosis

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Sep 2

PMID 39219209

Authors

Matthew D Howe

Megan R Caruso

Masood Manoochehri

Zachary J Kunicki

Sheina Emrani

James L Rudolph

Edward D Huey

Stephen P Salloway

Hwamee Oh

Affiliations

Soon will be listed here.

Abstract

Introduction: The relationship between cerebrovascular disease (CVD) and amyloid beta (Aβ) in Alzheimer's disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers-including cerebral microbleeds (CMBs), lacunar infarction, and white matter hyperintensities (WMHs)-would correlate with Aβ positivity on positron emission tomography (Aβ-PET).

Methods: We cross-sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth.

Results: Following adjustment, WMHs (OR = 1.25) and superficial CMBs (OR = 1.45) remained positively associated with Aβ-PET positivity (p < 0.001). Deep CMBs and lacunes exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R= 0.41).

Discussion: The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria.

Clinicaltrials: gov: ADNI-2 (NCT01231971), ADNI-3 (NCT02854033).

Highlights: Cerebrovascular biomarkers linked to amyloid beta (Aβ) in Alzheimer's disease (AD). White matter hyperintensities and cerebral microbleeds reliably predict Aβ-PET positivity. Relationships with Aβ-PET vary by cognitive stage. Novel accessible model predicts Aβ-PET status. Study supports multimodal diagnostic approaches.

Citing Articles

Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis.

Howe M, Caruso M, Manoochehri M, Kunicki Z, Emrani S, Rudolph J Alzheimers Dement. 2024; 20(10):7220-7231.

PMID: 39219209 PMC: 11485066. DOI: 10.1002/alz.14207.

References

Landau S, Breault C, Joshi A, Pontecorvo M, Mathis C, Jagust W . Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2012; 54(1):70-7. PMC: 3747730. DOI: 10.2967/jnumed.112.109009. View

Huijts M, Duits A, van Oostenbrugge R, Kroon A, de Leeuw P, Staals J . Accumulation of MRI Markers of Cerebral Small Vessel Disease is Associated with Decreased Cognitive Function. A Study in First-Ever Lacunar Stroke and Hypertensive Patients. Front Aging Neurosci. 2013; 5:72. PMC: 3818574. DOI: 10.3389/fnagi.2013.00072. View

Howe M, McCullough L, Urayama A . The Role of Basement Membranes in Cerebral Amyloid Angiopathy. Front Physiol. 2020; 11:601320. PMC: 7732667. DOI: 10.3389/fphys.2020.601320. View

Howe M, Atadja L, Furr J, Maniskas M, Zhu L, McCullough L . Fibronectin induces the perivascular deposition of cerebrospinal fluid-derived amyloid-β in aging and after stroke. Neurobiol Aging. 2018; 72:1-13. PMC: 6219378. DOI: 10.1016/j.neurobiolaging.2018.07.019. View

Howe M, Britton K, Joyce H, Pappas G, Faust M, Dawson B . Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval. J Prev Alzheimers Dis. 2023; 10(4):765-770. DOI: 10.14283/jpad.2023.96. View

Harper L, Barkhof F, Scheltens P, Schott J, Fox N . An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry. 2013; 85(6):692-8. PMC: 4033032. DOI: 10.1136/jnnp-2013-306285. View

Garnier-Crussard A, Cotton F, Krolak-Salmon P, Chetelat G . White matter hyperintensities in Alzheimer's disease: Beyond vascular contribution. Alzheimers Dement. 2023; 19(8):3738-3748. DOI: 10.1002/alz.13057. View

Luo J, Ma Y, Agboola F, Grant E, Morris J, McDade E . Longitudinal Relationships of White Matter Hyperintensities and Alzheimer Disease Biomarkers Across the Adult Life Span. Neurology. 2023; 101(2):e164-e177. PMC: 10351551. DOI: 10.1212/WNL.0000000000207378. View

Walsh P, Sudre C, Fiford C, Ryan N, Lashley T, Frost C . CSF amyloid is a consistent predictor of white matter hyperintensities across the disease course from aging to Alzheimer's disease. Neurobiol Aging. 2020; 91:5-14. DOI: 10.1016/j.neurobiolaging.2020.03.008. View

10.

Shah N, Vidal J, Masaki K, Petrovitch H, Ross G, Tilley C . Midlife blood pressure, plasma β-amyloid, and the risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension. 2012; 59(4):780-6. PMC: 3319436. DOI: 10.1161/HYPERTENSIONAHA.111.178962. View

11.

Filshtein T, Dugger B, Jin L, Olichney J, Farias S, Carvajal-Carmona L . Neuropathological Diagnoses of Demented Hispanic, Black, and Non-Hispanic White Decedents Seen at an Alzheimer's Disease Center. J Alzheimers Dis. 2019; 68(1):145-158. PMC: 7286069. DOI: 10.3233/JAD-180992. View

12.

Santos C, Snyder P, Wu W, Zhang M, Echeverria A, Alber J . Pathophysiologic relationship between Alzheimer's disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis. Alzheimers Dement (Amst). 2017; 7:69-87. PMC: 5328683. DOI: 10.1016/j.dadm.2017.01.005. View

13.

Gorelick P, Scuteri A, Black S, DeCarli C, Greenberg S, Iadecola C . Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011; 42(9):2672-713. PMC: 3778669. DOI: 10.1161/STR.0b013e3182299496. View

14.

Weiner M, Veitch D, Aisen P, Beckett L, Cairns N, Green R . The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement. Alzheimers Dement. 2016; 13(5):561-571. PMC: 5536850. DOI: 10.1016/j.jalz.2016.10.006. View

15.

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

16.

Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski J, Bittner T . CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement. 2018; 14(11):1470-1481. PMC: 6119541. DOI: 10.1016/j.jalz.2018.01.010. View

17.

Hansson O, Blennow K, Zetterberg H, Dage J . Blood biomarkers for Alzheimer's disease in clinical practice and trials. Nat Aging. 2023; 3(5):506-519. PMC: 10979350. DOI: 10.1038/s43587-023-00403-3. View

18.

Royse S, Minhas D, Lopresti B, Murphy A, Ward T, Koeppe R . Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach. Alzheimers Res Ther. 2021; 13(1):99. PMC: 8111744. DOI: 10.1186/s13195-021-00836-1. View

19.

Ii Y, Ishikawa H, Shindo A, Matsuyama H, Matsuura K, Matsuda K . Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3-Tesla magnetic resonance imaging. Eur J Neurol. 2020; 28(3):794-799. DOI: 10.1111/ene.14610. View

20.

Tsai H, Pasi M, Tsai L, Chen Y, Lee B, Tang S . Distribution of Lacunar Infarcts in Asians With Intracerebral Hemorrhage: A Magnetic Resonance Imaging and Amyloid Positron Emission Tomography Study. Stroke. 2018; 49(6):1515-1517. PMC: 5971000. DOI: 10.1161/STROKEAHA.118.021539. View