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; 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

doi:10.1186/s13195-023-01243-4

Alzheimer's Research & Therapy

Table 4 Posterior WMH mediate the effects of hypertension and Aβ positivity on cognitive performance

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

Dependent variable	Mediator variable^a	Hypertension			Aβ positivity
		Direct effect	Indirect effect	Total effect	Direct effect	Indirect effect	Total effect
		B (SE); p_FDR	B (SE); p_FDR	B (SE); p_FDR	B (SE); p_FDR	B (SE); p_FDR	B (SE); p_FDR
Baseline memory (n = 375)	Global	0.06 (0.07); 0.433	− 0.03 (0.02); 0.083	0.03 (0.07); 0.666	− 0.33 (0.07); < 0.001	− 0.03 (0.02); 0.133	− 0.36 (0.08); < 0.001
	Frontal	0.05 (0.07); 0.500	− 0.02 (0.01); 0.162	0.03 (0.07); 0.666	− 0.33 (0.08); < 0.001	− 0.02 (0.02); 0.179	− 0.36 (0.08); < 0.001
	Occipital	0.07 (0.07); 0.433	− 0.04 (0.02); 0.083	0.03 (0.07); 0.666	− 0.33 (0.08); < 0.001	− 0.03 (0.02); 0.117	− 0.36 (0.08); < 0.001
	Parietal	0.07 (0.07); 0.433	− 0.04 (0.02); 0.083	0.03 (0.07); 0.666	− 0.33 (0.08); < 0.001	− 0.03 (0.02); 0.111	− 0.36 (0.08); < 0.001
	Corona radiata	0.06 (0.07); 0.452	− 0.03 (0.02); 0.106	0.03 (0.07); 0.666	− 0.33 (0.08); < 0.001	− 0.02 (0.02); 0.129	− 0.36 (0.08); < 0.001
	Optic radiation	0.06 (0.07); 0.464	− 0.03 (0.02); 0.128	0.03 (0.07); 0.666	− 0.31 (0.08); < 0.001	− 0.05 (0.02); 0.029	− 0.36 (0.08); < 0.001
	Splenium	0.08 (0.07); 0.349	− 0.05 (0.02); 0.029	0.03 (0.08); 0.666	− 0.32 (0.08); < 0.001	− 0.04 (0.02); 0.102	− 0.36 (0.08); < 0.001
Baseline executive (n = 375)	Global	− 0.06 (0.07); 0.455	− 0.03 (0.01); 0.112	− 0.09 (0.07); 0.294	− 0.21 (0.08); 0.029	− 0.02 (0.02); 0.209	− 0.23 (0.08); 0.014
	Frontal	− 0.07 (0.07); 0.433	− 0.02 (0.01); 0.208	− 0.09 (0.07); 0.294	− 0.21 (0.08); 0.030	− 0.02 (0.02); 0.256	− 0.23 (0.08); 0.014
	Occipital	− 0.07 (0.07); 0.383	− 0.01 (0.01); 0.387	− 0.09 (0.07); 0.294	− 0.22 (0.08); 0.023	− 0.01 (0.01); 0.433	− 0.23 (0.08); 0.014
	Parietal	− 0.06 (0.07); 0.451	− 0.02 (0.02); 0.180	− 0.09 (0.07); 0.294	− 0.21 (0.08); 0.029	− 0.02 (0.01); 0.274	− 0.23 (0.08); 0.014
	Corona radiata	− 0.07 (0.07); 0.452	− 0.025 (0.01); 0.134	− 0.09 (0.07); 0.294	− 0.21 (0.08); 0.029	− 0.02 (0.02); 0.190	− 0.23 (0.08); 0.014
	Optic radiation	− 0.08 (0.07); 0.370	− 0.01 (0.01); 0.370	− 0.09 (0.07); 0.294	− 0.21 (0.08); 0.029	− 0.02 (0.02); 0.365	− 0.23 (0.08); 0.014
	Splenium	− 0.05 (0.07); 0.542	− 0.04 (0.02); 0.067	− 0.09 (0.07); 0.294	− 0.20 (0.08); 0.035	− 0.03 (0.02); 0.180	− 0.23 (0.08); 0.014
Baseline PACC5 (n = 375)	Global	0.08 (0.07); 0.368	− 0.03 (0.02); 0.083	0.04 (0.07); 0.547	− 0.29 (0.08); 0.006	− 0.03 (0.02); 0.149	− 0.32 (0.09); < 0.001
	Frontal	0.07 (0.07); 0.405	− 0.03 (0.02); 0.151	0.05 (0.07); 0.547	− 0.29 (0.09); 0.006	− 0.03 (0.02); 0.178	− 0.32 (0.09); < 0.001
	Occipital	0.07 (0.07); 0.420	− 0.02 (0.01); 0.164	0.05 (0.07); 0.547	− 0.29 (0.09); 0.006	− 0.02 (0.02); 0.215	− 0.32 (0.09); < 0.001
	Parietal	0.07 (0.07); 0.379	− 0.03 (0.02); 0.102	0.05 (0.07); 0.547	− 0.28 (0.09); 0.006	− 0.03 (0.02); 0.149	− 0.32 (0.09); < 0.001
	Corona radiata	0.07 (0.07); 0.379	− 0.03 (0.02); 0.098	0.05 (0.07); 0.547	− 0.29 (0.09); 0.006	− 0.03 (0.02); 0.128	− 0.32 (0.09); < 0.001
	Optic radiation	0.07 (0.07); 0.432	− 0.02 (0.01); 0.155	0.05 (0.07); 0.547	− 0.27 (0.09); 0.012	− 0.04 (0.02); 0.067	− 0.32 (0.09); < 0.001
	Splenium	0.10 (0.07); 0.279	− 0.05 (0.02); 0.030	0.05 (0.07); 0.547	− 0.27 (0.09); 0.012	− 0.04 (0.02); 0.120	− 0.32 (0.09); < 0.001
ΔPACC5 (n = 226)	Global	− 0.10 (0.13); 0.496	− 0.06 (0.03); 0.095	− 0.16 (0.13); 0.294	− 0.35 (0.14); 0.041	− 0.04 (0.03); 0.370	− 0.38 (0.15); 0.029
	Frontal	− 0.11 (0.13); 0.448	− 0.05 (0.03); 0.172	− 0.16 (0.13); 0.294	− 0.33 (0.14); 0.058	− 0.06 (0.04); 0.208	− 0.38 (0.15); 0.029
	Occipital	− 0.09 (0.13); 0.547	− 0.08 (0.04); 0.084	− 0.16 (0.13); 0.294	− 0.32 (0.14); 0.069	− 0.06 (0.03); 0.134	− 0.38 (0.15); 0.029
	Parietal	− 0.10 (0.13); 0.486	− 0.06 (0.03); 0.121	− 0.16 (0.13); 0.294	− 0.34 (0.14); 0.050	− 0.04 (0.03); 0.208	− 0.38 (0.15); 0.029
	Corona radiata	− 0.11 (0.13); 0.464	− 0.06 (0.03); 0.121	− 0.16 (0.13); 0.294	− 0.34 (0.14); 0.043	− 0.03 (0.03); 0.352	− 0.38 (0.15); 0.029
	Optic radiation	− 0.10 (0.13); 0.471	− 0.06 (0.03); 0.162	− 0.16 (0.13); 0.294	− 0.30 (0.14); 0.083	− 0.07 (0.03); 0.083	− 0.38 (0.15); 0.029
	Splenium	− 0.08 (0.13); 0.572	− 0.09 (0.03); 0.043	− 0.16 (0.13); 0.294	− 0.34 (0.14); 0.048	− 0.04 (0.02); 0.250	− 0.38 (0.15); 0.029

We tested for indirect mediating effects of arterial hypertension and Aβ positivity (independent variables) on cognitive performance (dependent variable) via regional WMH volume (mediator variable) (Fig. 1). The significance of p-values for these associations was based on 95% confidence intervals generated using bias-corrected bootstrap with 1000 replicates. We controlled for hypertension, age, sex, education, mean background intensity, and total intracranial volume. We print p_FDR < 0.05 in bold
^aWe log-transformed WMH volumes to deal with skewness
p_FDR, p-values after adjusting for multiple comparisons using FDR; n sample size, B regression coefficient, SE standard error

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