An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF Aβ42 and an APOE ε4 allele

NEUROBIOLOGY OF DISEASE

卷:127

Article

Shahid, Marian¹  Kim, Jeehyun¹  Leaver, Katherine^1,2  Hendershott, Taylor¹  Zhu, Delphine¹  Cholerton, Brenna³  Henderson, Victor W.^1,4  Tian, Lu⁵  Poston, Kathleen L.^1,6 

[1] Stanford Univ, Dept Neurol & Neurol Sci, 300 Pasteur Dr,Room H3144,MC 5235, Stanford, CA 94305 USA

[2] Mt Sinai Beth Israel, Dept Neurol, 10 Union Sq East, New York, NY 10003 USA

[3] Stanford Univ, Dept Pathol, 300 Pasteur Dr Rm L235,MC 5324, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Hlth Res & Policy Epidemiol, 259 Campus Dr,MC 5405, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Biomed Data Sci, 150 Governors Lane,Room T160C,MC 5464, Stanford, CA 94305 USA

[6] Stanford Univ, Dept Neurosurg, 300 Pasteur Dr,Room H3144,MC 5235, Stanford, CA 94305 USA

关键词: Parkinson's disease;    Cognitive impairment;    APOE epsilon 4;    Amyloid;    Cerebrospinal fluid;   

DOI  :  10.1016/j.nbd.2019.02.023

来源: Elsevier

【 摘 要 】

Objective: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (A beta-42) are associated with increased risk of cognitive decline in Parkinson's disease (PD). We sought to determine whether APOE genotype modifies the rate of cognitive decline in PD patients with low CSF A beta-42 compared to patients with normal levels. Methods: The Parkinson's Progression Markers Initiative is a longitudinal, ongoing study of de novo PD participants, which includes APOE genotyping, CSF A beta-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF A beta at baseline, PD participants with normal CSF A beta, and both groups combined). Having at least one copy of the APOE epsilon 4 allele, time, and the interaction of APOE epsilon 4 and time were predictor variables for cognitive change, adjusting for age, gender and education. Results: 423 de novo PD participants were followed up to 5 years with annual cognitive assessments. 103 participants had low baseline CSF A beta-42 (39 APOE epsilon 4+, 64 APOE epsilon 4-). Compared to participants with normal CSF A beta-42, those with low CSF A beta-42 declined faster on most cognitive tests. Within the low CSF A beta-42 group, APOE epsilon 4+ participants had faster rates of decline on the Montreal Cognitive Assessment (primary outcome; 0.57 points annual decline, p = .005; 5-year standardized change of 1.2) and the Symbol Digit Modalities Test (1.4 points annual decline, p = .002; 5-year standardized change of 0.72). Discussion: PD patients with low CSF A beta-42 and APOE epsilon 4+ showed a higher rate of cognitive decline early in the disease. Tests of global cognition (Montreal Cognitive Assessment) and processing speed (Symbol Digit Modalities Test) were the most sensitive to early cognitive decline. Results suggest that CSF A beta-42 and APOE epsilon 4 might interact to promote early cognitive changes in PD patients.

【 授权许可】

Free