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

被引：12

作者：

Bernal, Jose ^{[1
,2
]}

Schreiber, Stefanie ^{[2
,3
]}

Menze, Inga ^{[1
,2
]}

Ostendorf, Anna ^{[1
]}

Pfister, Malte ^{[3
]}

Geisendoerfer, Jonas ^{[3
]}

Nemali, Aditya ^{[1
,2
]}

Maass, Anne ^{[2
]}

Yakupov, Renat ^{[2
]}

Peters, Oliver ^{[4
,5
,6
,7
,8
]}

Preis, Lukas ^{[5
,6
,7
,8
]}

Schneider, Luisa ^{[5
,6
,7
,8
]}

Herrera, Ana Lucia ^{[5
,6
,7
,8
]}

Priller, Josef ^{[4
,9
,10
,11
,12
]}

Spruth, Eike Jakob ^{[4
,9
]}

Altenstein, Slawek ^{[4
,9
]}

Schneider, Anja ^{[13
,14
]}

Fliessbach, Klaus ^{[13
,14
]}

Wiltfang, Jens ^{[15
,16
,17
]}

Schott, Bjoern H. ^{[15
,16
]}

Rostamzadeh, Ayda ^{[18
]}

Glanz, Wenzel ^{[1
]}

Buerger, Katharina ^{[19
,20
]}

Janowitz, Daniel ^{[20
]}

Ewers, Michael ^{[19
,20
]}

Perneczky, Robert ^{[19
,21
,22
,23
,24
]}

Rauchmann, Boris-Stephan ^{[21
]}

Teipel, Stefan ^{[25
,26
]}

Kilimann, Ingo ^{[25
,26
]}

Laske, Christoph ^{[27
,28
,29
]}

Munk, Matthias H. ^{[27
,29
]}

Spottke, Annika ^{[13
,14
]}

Roy, Nina ^{[13
]}

Dobisch, Laura ^{[2
]}

Dechent, Peter ^{[30
]}

Scheffler, Klaus ^{[31
]}

Hetzer, Stefan ^{[32
]}

Wolfsgruber, Steffen ^{[13
,14
]}

Kleineidam, Luca ^{[13
,14
]}

Schmid, Matthias ^{[13
,33
]}

Berger, Moritz ^{[33
]}

Jessen, Frank ^{[13
,18
,34
]}

Wirth, Miranka ^{[35
]}

Duezel, Emrah ^{[1
,2
,36
]}

Ziegler, Gabriel ^{[1
,2
]}

机构：

[1] Otto von Guericke Univ, Inst Cognit Neurol & Dementia Res, Magdeburg, Germany

[2] German Ctr Neurodegenerat Dis DZNE, Leipziger Str 44, D-39120 Magdeburg, Germany

[3] Univ Hosp Magdeburg, Med Fac, Dept Neurol, Magdeburg, Germany

[4] German Ctr Neurodegenerat Dis DZNE, Berlin, Germany

[5] Charite Univ Med Berlin, Berlin, Germany

[6] Free Univ Berlin, Berlin, Germany

[7] Humboldt Univ, Berlin, Germany

[8] Inst Psychiat & Psychotherapy, Berlin, Germany

[9] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany

[10] Tech Univ Munich, Dept Psychiat & Psychotherapy, Sch Med, Munich, Germany

[11] Univ Edinburgh, Edinburgh, Midlothian, Scotland

[12] UK DRI, Edinburgh, Midlothian, Scotland

[13] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[14] Univ Bonn, Clin Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany

[15] German Ctr Neurodegenerat Dis DZNE, Gottingen, Germany

[16] Univ Goettingen, Univ Med Ctr Goettingen, Dept Psychiat & Psychotherapy, Gottingen, Germany

[17] Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, Neurosci & Signaling Grp, Aveiro, Portugal

[18] Univ Cologne, Dept Psychiat, Cologne, Germany

[19] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[20] Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany

[21] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Psychiat & Psychotherapy, Munich, Germany

[22] Munich Cluster Syst Neurol SyNergy Munich, Munich, Germany

[23] Imperial Coll London, Sch Publ Hlth, Ageing Epidemiol Res Unit AGE, London, England

[24] Univ Sheffield, Sheffield Inst Translat Neurosci SITraN, Sheffield, S Yorkshire, England

[25] German Ctr Neurodegenerat Dis DZNE, Rostock, Germany

[26] Rostock Univ, Med Ctr, Dept Psychosomat Med, Rostock, Germany

[27] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[28] Univ Tubingen, Hertie Inst Clin Brain Res, Sect Dementia Res, Tubingen, Germany

[29] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany

[30] Georg August Univ Goettingen, Dept Cognit Neurol, MR Res Neurosci, Gottingen, Germany

[31] Univ Tubingen, Dept Biomed Magnet Resonance, Tubingen, Germany

[32] Charite Univ Med Berlin, Berlin Ctr Adv Neuroimaging, Berlin, Germany

[33] Univ Hosp Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany

[34] Univ Cologne, Excellence Cluster Cellular Stress Responses Agin, Cologne, Germany

[35] German Ctr Neurodegenerat Dis DZNE, Tatzberg 41, D-01307 Dresden, Germany

[36] UCL, Inst Cognit Neurosci, London, England

来源：

ALZHEIMERS RESEARCH & THERAPY | 2023年 / 15卷 / 01期

关键词：

White matter hyperintensities; Vascular risk; Alzheimer's disease; Cognitive performance; MRI; SMALL VESSEL DISEASE; SUBJECTIVE COGNITIVE DECLINE; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; ANGIOPATHY; DEMENTIA; ASSOCIATION; IMPAIRMENT; DIAGNOSIS;

D O I：

10.1186/s13195-023-01243-4

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页数：13

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