Age-Related Association Between APOE ɛ4 and Cognitive Progression in de novo Parkinson’s Disease

Article type: Research Article

Authors: Liu, Jia-Yao^{a; 1} | Ma, Ling-Zhi^{a; 1} | Wang, Jun^{b; c} | Cui, Xin-Jing^d | Sheng, Ze-Hu^a | Fu, Yan^a | Li, Meng^a | Ou, Ya-Nan^a | Yu, Jin-Tai^{e; *} | Tan, Lan^{a; *} | Lian, Yan^{b; f; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [b] Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China | [c] Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China | [d] Department of Outpatient, Qingdao Municipal Hospital, Qingdao, China | [e] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [f] Department of Prevention and Health Care, Daping Hospital, Third Military Medical University, Chongqing, China

Correspondence: [*] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: [email protected] and Prof. Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China. E-mail: [email protected] and Prof. Yan Lian, PhD, Department of Prevention and Health Care, Daping Hospital, Third Military Medical University, Chongqing 400042, China. E-mail: [email protected].

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

Abstract: Background:APOE ɛ4 genotype was correlated with exacerbation of pathology and higher risk of dementia in Parkinson’s disease (PD). Meanwhile, the differential influence of APOE ɛ4 on cognition in young and old individuals interpreted as antagonistic pleiotropy. Objective:To examine whether the effect of APOE ɛ4 on cognitive progression in de novo PD is age dependent. Methods:In this study, 613 de novo PD patients were recruited from Parkinson’s Progression Markers Initiative (PPMI). To examine the age-dependent relationship between APOE ɛ4 and cognitive changes, we added 3-way interaction of APOE ɛ4*baseline age*time to the linear mixed-effect (LME) models and evaluated the specific roles of APOE ɛ4 in the middle age group and elderly group separately. Cox regression was utilized to examine the progression of cognition in age-stratified PD participants. Results:Age significantly modified relationship between APOE ɛ4 and cognitive changes in most cognitive domains (pinteraction <0.05). In the elderly group, APOE ɛ4 carriers showed steeper decline in global cognition (p = 0.001) as well as in most cognitive domains, and they had a greater risk of cognitive progression (adjusted HR 1.625, 95% CI 1.143–2.310, p = 0.007), compared with non-carriers. However, in the middle age group, no significant relationships between APOE ɛ4 and cognitive decline can be detected. Conclusion:Our results indicated that the APOE ɛ4 allele has an age-dependent effect on cognitive decline in PD patients. The underlying mechanisms need to be investigated in the future.

Keywords: Age, APOE ɛ4, cognition, Parkinson’s disease

DOI: 10.3233/JAD-220976

Journal: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1121-1132, 2023