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

Bernal, Jose; Schreiber, Stefanie; Menze, Inga; Ostendorf, Anna; Pfister, Malte; Geisendoerfer, 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, Bjoern 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; Duezel, Emrah und Ziegler, Gabriel (2023): Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study. In: Alzheimers Research & Therapy, Bd. 15, Nr. 1, 97

Abstract

BackgroundWhite 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.MethodsWe 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 (Delta PACC5).ResultsSubjects with hypertension or A beta positivity presented the largest WMH volumes (p(FDR) < 0.05), with spatial overlap in the frontal (hypertension: 0.42 +/- 0.17;A beta: 0.46 +/- 0.18), occipital (hypertension: 0.50 +/- 0.16;A beta: 0.50 +/- 0.16), parietal lobes (hypertension: 0.57 +/- 0.18;A beta: 0.56 +/- 0.20), corona radiata (hypertension: 0.45 +/- 0.17;A beta: 0.40 +/- 0.13), optic radiation (hypertension: 0.39 +/- 0.18;A beta: 0.74 +/- 0.19), and splenium of the corpus callosum (hypertension: 0.36 +/- 0.12;A beta: 0.28 +/- 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (p(FDR) < 0.05). A beta positivity was negatively associated with cognitive performance (direct effect-memory: - 0.33 +/- 0.08, p(FDR) < 0.001;executive: - 0.21 +/- 0.08, p(FDR) < 0.001;PACC5: - 0.29 +/- 0.09, p(FDR) = 0.006;Delta PACC5: - 0.34 +/- 0.04, p(FDR) < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect-memory: - 0.05 +/- 0.02, p(FDR) = 0.029;executive: - 0.04 +/- 0.02, p(FDR) = 0.067;PACC5: - 0.05 +/- 0.02, p(FDR) = 0.030;Delta PACC5: - 0.09 +/- 0.03, p(FDR) = 0.043) and WMH in the optic radiation partially mediated that between A beta positivity and memory (indirect effect-memory: - 0.05 +/- 0.02, p(FDR) = 0.029).ConclusionsPosterior white matter is susceptible to hypertension and A beta accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198