Arterial hypertension and [beta]-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

• Published in: Alzheimer's research & therapy 2023-05, Vol.15 (1)
• Main Authors: Bernal, Jose, Schreiber, Stefanie, Menze, Inga, Ostendorf, Anna, Pfister, Malte, Geisendörfer, Jonas, Nemali, Aditya, Maass, Anne, Yakupov, Renat, Peters, Oliver, Preis, Lukas, Schneider, Luisa, Herrera, Ana Lucia, Priller, Josef, Spruth, Eike Jakob, Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H, Rostamzadeh, Ayda, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Ewers, Michael, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H, Spottke, Annika, Roy, Nina, Dobisch, Laura, Dechent, Peter, Scheffler, Klaus, Hetzer, Stefan, Wolfsgruber, Steffen, Kleineidam, Luca, Schmid, Matthias, Berger, Moritz, Jessen, Frank, Wirth, Miranka, Düzel, Emrah, Ziegler, Gabriel
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-protein; Complications and side effects; Development and progression; Health aspects; Hypertension; Risk factors
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-023-01243-4

Background White matter hyperintensities (WMH) in subjects across the Alzheimer's disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology--not just arterial hypertension--impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and A[beta] positivity on WMH, and their impact on cognition. Methods We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function--derived from multiple neuropsychological tests using confirmatory factor analysis--, baseline preclinical Alzheimer's cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years ([DELA]PACC5). Results Subjects with hypertension or A[beta] positivity presented the largest WMH volumes (p.sub.FDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 [+ or -] 0.17; A[beta]: 0.46 [+ or -] 0.18), occipital (hypertension: 0.50 [+ or -] 0.16; A[beta]: 0.50 [+ or -] 0.16), parietal lobes (hypertension: 0.57 [+ or -] 0.18; A[beta]: 0.56 [+ or -] 0.20), corona radiata (hypertension: 0.45 [+ or -] 0.17; A[beta]: 0.40 [+ or -] 0.13), optic radiation (hypertension: 0.39 [+ or -] 0.18; A[beta]: 0.74 [+ or -] 0.19), and splenium of the corpus callosum (hypertension: 0.36 [+ or -] 0.12; A[beta]: 0.28 [+ or -] 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (p.sub.FDR < 0.05). A[beta] positivity was negatively associated with cognitive performance (direct effect--memory: - 0.33 [+ or -] 0.08, p.sub.FDR < 0.001; executive: - 0.21 [+ or -] 0.08, p.sub.FDR < 0.001; PACC5: - 0.29 [+ or -] 0.09, p.sub.FDR = 0.006; [DELA]PACC5: - 0.34 [+ or -] 0.04, p.sub.FDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect--memory: - 0.05 [+ or -] 0.02, p.sub.FDR = 0.029; executive: - 0.04 [+ or -] 0.02, p.sub.FDR = 0.067; PACC5: - 0.05 [+ or -] 0.02, p.sub.FDR = 0.030; [DELA]PACC5: - 0.09 [+ or -] 0.03, p.sub.FDR = 0.043) and WMH in the optic radiation partially