Associations of White Matter Hyperintensities with Cognitive Decline: A Longitudinal Study

Article type: Research Article

Authors: Wang, Yan-Li^{a; 1} | Chen, Wei^{a; 1} | Cai, Wen-Jie^{c; 1} | Hu, Hao^a | Xu, Wei^a | Wang, Zuo-Teng^a | Cao, Xi-Peng^b | Tan, Lan^{a; *} | Yu, Jin-Tai^{c; *} | Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [b] Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [c] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Dr. Jin-Tai Yu, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. E-mail: yu-jintai@163.com; Dr. Lan Tan, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao, China. E-mail: dr.tanlan@163.com.

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer’s disease (AD) dementia compared with controls (p < 0.001) and mild cognitive impairment (p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD.

Keywords: Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, cognition, white matter hyperintensities

DOI: 10.3233/JAD-191005

Journal: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 759-768, 2020