Inherited risk of dementia and the progression of cerebral small vessel disease and inflammatory markers in cognitively healthy midlife adults: the PREVENT-Dementia study

NEUROBIOLOGY OF AGING

卷:98

Article

Low, Audrey¹  Su, Li¹  Stefaniak, James D.^2,3  Mak, Elijah¹  Dounavi, Maria-Eleni¹  Muniz-Terrera, Graciela⁴  Ritchie, Karen^4,5  Ritchie, Craig W.⁴  Markus, Hugh S.²  O'Brien, John T.¹ 

[1] Univ Cambridge, Sch Clin Med, Dept Psychiat, Cambridge Biomedical Campus,Box 189,Level E4, Cambridge CB2 0SP, Cambs, England

[2] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[3] Univ Manchester, Div Neurosci & Expt Psychol, Manchester, Lancs, England

[4] Univ Edinburgh, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland

[5] INSERM, Montpellier, France

关键词: Cerebral small vessel disease;    White matter hyperintensities;    Cerebral microbleeds;    Inflammation;    Alzheimer's disease;    APOE4;    Risk factors;   

DOI  :  10.1016/j.neurobiolaging.2020.10.029

来源: Elsevier

【 摘 要 】

Cerebral small vessel disease (SVD) and inflammation are increasingly recognized as key contributors to Alzheimer's disease (AD), although the timing, trajectory, and relation between them early in the disease process is unclear. Therefore, to investigate very early-stage changes, we compared 158 healthy midlife adults with and without inherited AD predisposition (APOE4 carriership (38% positive), parental family history (FH) of dementia (54% positive)) on markers of SVD (white matter hyperintensities (WMH), cerebral microbleeds), and inflammation (C-reactive protein (CRP), fibrinogen), cross-sectionally and longitudinally over two years. While WMH severity was comparable between groups at baseline, longitudinal progression of WMH was greater in at-risk groups (APOE4+ and FH+). Topographically, APOE4 was associated exclusively with deep, but not periventricular, WMH progression after adjusting for FH. Conversely, APOE4 carriers displayed lower CRP levels than noncarriers, but not fibrinogen. Furthermore, interaction analysis showed that FH moderated the effect of SVD and inflammation on reaction time, an early feature of SVD, but not episodic memory or executive function. Findings suggest that vascular and inflammatory changes could occur decades before dementia onset, and may be of relevance in predicting incipient clinical progression. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

【 授权许可】

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