An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF Aß42 and an APOE ε4 allele

Marian Shahid; Jeehyun Kim; Katherine Leaver; Taylor Hendershott; Delphine Zhu; Brenna Cholerton; Victor W. Henderson; Lu Tian; Kathleen L. Poston

Neurobiology of Disease (Jul 2019)

An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF Aß42 and an APOE ε4 allele

Marian Shahid,
Jeehyun Kim,
Katherine Leaver,
Taylor Hendershott,
Delphine Zhu,
Brenna Cholerton,
Victor W. Henderson,
Lu Tian,
Kathleen L. Poston

Affiliations

Marian Shahid: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America
Jeehyun Kim: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America
Katherine Leaver: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America; Mount Sinai Beth Israel, Department of Neurology, 10 Union Square East, New York, NY 10003, United States of America
Taylor Hendershott: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America
Delphine Zhu: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America
Brenna Cholerton: Stanford University, Department of Pathology, 300 Pasteur Dr Rm L235, MC 5324, Stanford, CA 94305, United States of America
Victor W. Henderson: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America; Stanford University, Department of Health Research and Policy (Epidemiology), 259 Campus Drive, MC 5405, Stanford, CA 94305, United States of America
Lu Tian: Stanford University, Department of Biomedical Data Science, 150 Governor's Lane, Room T160C, MC 5464, Stanford, CA 94305, United States of America
Kathleen L. Poston: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America; Stanford University, Department of Neurosurgery, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America; Corresponding author at: Stanford University, Department of Neurology and Neurological Sciences, 300 Pasteur Dr. Room H3144, MC 5235, Stanford, CA 94305, United States of America.

Journal volume & issue: Vol. 127
pp. 278 – 286

Abstract

Read online

Objective: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (Aβ-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 Aβ-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 Aβ-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF Aβ at baseline, PD participants with normal CSF Aβ, and both groups combined). Having at least one copy of the APOE ɛ4 allele, time, and the interaction of APOE ɛ4 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 Aβ-42 (39 APOE ε4+, 64 APOE ε4-). Compared to participants with normal CSF Aβ-42, those with low CSF Aβ-42 declined faster on most cognitive tests. Within the low CSF Aβ-42 group, APOE ε4+ 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 Aβ-42 and APOE ε4+ 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 Aβ-42 and APOE ε4 might interact to promote early cognitive changes in PD patients.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords