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Abstract
Background and Objectives One of the most prevalent chronic diseases, osteoarthritis (OA), may work in conjunction with APOE-ε4 to accelerate Alzheimer disease (AD) alterations, particularly in the primary motor (precentral) and somatosensory (postcentral) cortices. To understand the reasoning behind this, we investigated how OA and APOE-ε4 influence the accumulation of β-amyloid (Aβ) and tau accumulation in primary motor and somatosensory regions in Aβ-positive (Aβ+) older individuals.
Methods We selected Aβ+ Alzheimer Disease Neuroimaging Initiative participants, defined by baseline 18F-florbetapir (FBP) Aβ PET standardized uptake value ratio (SUVR) of AD summary cortical regions, who had longitudinal Aβ PET, the records of OA medical history, and APOE-ε4 genotyping. We examined how OA and APOE-ε4 relate to baseline and longitudinal Aβ accumulation and tau deposition measured at follow-up in precentral and postcentral cortical areas and how they modulate Aβ-associated future higher tau levels, adjusting for age, sex, and diagnosis and using multiple comparison corrections.
Results A total of 374 individuals (mean age 75 years, 49.2% female, 62.8% APOE-ε4 carriers) who underwent longitudinal FBP PET with a median follow-up of 3.3 years (interquartile range [IQR] 3.4, range 1.6–9.4) were analyzed, and 96 people had 18F-flortaucipir (FTP) tau PET measured at a median of 5.4 (IQR 1.9, range 4.0–9.3) years postbaseline FBP PET. Neither OA nor APOE-ε4 was related to baseline FBP SUVR in precentral and postcentral regions. At follow-up, OA rather than APOE-ε4 was associated with faster Aβ accumulation in postcentral region (β = 0.005, 95% CI 0.001–0.008) over time. In addition, OA but not the APOE-ε4 allele was strongly linked to higher follow-up FTP tau levels in precentral (β = 0.098, 95% CI 0.034–0.162) and postcentral (β = 0.105, 95% CI 0.040–0.169) cortices. OA and APOE-ε4 were also interactively associated with higher follow-up FTP tau deposition in precentral (β = 0.128, 95% CI 0.030–0.226) and postcentral (β = 0.124, 95% CI 0.027–0.223) regions.
Discussion This study suggests that OA was associated with faster Aβ accumulation and higher Aβ-dependent future tau deposition in primary motor and somatosensory regions, providing novel insights into how OA increases the risk of AD.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer Disease Neuroimaging Initiative;
- CI=
- cognitively impaired;
- CU=
- cognitively unimpaired;
- GLM=
- generalized linear model;
- IQR=
- interquartile range;
- MCI=
- mild cognitive impairment;
- OA=
- osteoarthritis;
- FBP=
- 18F-florbetapir;
- FTP=
- 18F-flortaucipir;
- ROI=
- region of interest;
- SPM=
- statistical parametric mapping;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Data used in preparation of this article were obtained from the Alzheimer Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of the 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 in Appendix 2 at links.lww.com/WNL/C803.
Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.
- Received August 2, 2022.
- Accepted in final form March 17, 2023.
- © 2023 American Academy of Neurology
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