The Interaction Between Vascular Risk Factors, Cerebral Small Vessel Disease, and Amyloid Burden in Older Adults

Article type: Research Article

Authors: Koncz, Rebecca^{a; b; c; *} | Wen, Wei^a | Makkar, Steve R.^a | Lam, Ben C.P.^a | Crawford, John D.^a | Rowe, Christopher C.^{d; e} | Sachdev, Perminder^{a; f} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, UNSW Sydney, NSW, Australia | [b] The University of Sydney Specialty of Psychiatry, Faculty of Medicine and Health, Concord, NSW, Australia | [c] Sydney Local Health District, Concord, NSW, Australia | [d] Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia | [e] Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia | [f] Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia

Correspondence: [*] Correspondence to: Dr. Rebecca Koncz, MBBS(Hons), MPsychiatry, FRANZCP, Centre for Healthy Brain Ageing, UNSW Sydney, UNSW Medicine, School of Psychiatry, Level 1, AGSM (G27), UNSW Sydney NSW 2052, Australia. E-mail: r.koncz@unsw.edu.au.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Cerebral small vessel disease (SVD) and Alzheimer’s disease pathology, namely amyloid-β (Aβ) deposition, commonly co-occur. Exactly how they interact remains uncertain. Objective:Using participants from the Alzheimer’s Disease Neuroimaging Initiative (n = 216; mean age 73.29±7.08 years, 91 (42.1%) females), we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of Aβ cross-sectionally, and at 24 months follow-up. Method:Amyloid burden, assessed using 18F-florbetapir PET, was quantified as the global standardized uptake value ratio (SUVR). Multimodal imaging was used to strengthen the quantification of baseline SVD as a composite variable, which included white matter hyperintensity volume using MRI, and peak width of skeletonized mean diffusivity using diffusion tensor imaging. Structural equation modeling was used to analyze the associations between demographic factors, Apolipoprotein E ɛ4 carrier status, vascular risk factors, SVD burden and cerebral amyloid. Results:SVD burden had a direct association with Aβ burden cross-sectionally (coeff. = 0.229, p = 0.004), and an indirect effect over time (indirect coeff. = 0.235, p = 0.004). Of the vascular risk factors, a history of hypertension (coeff. = 0.094, p = 0.032) and a lower fasting glucose at baseline (coeff. = –0.027, p = 0.014) had a direct effect on Aβ burden at 24 months, but only the direct effect of glucose persisted after regularization. Conclusion:While Aβ and SVD burden have an association cross-sectionally, SVD does not appear to directly influence the accumulation of Aβ longitudinally. Glucose regulation may be an important modifiable risk factor for Aβ accrual over time.

Keywords: Amyloid, cerebral small vessel disease, hypertension, peak width of skeletonized mean diffusivity, positron emission tomography, white matter hyperintensities

DOI: 10.3233/JAD-210358

Journal: Journal of Alzheimer's Disease, vol. 86, no. 4, pp. 1617-1628, 2022