Both osteoarthritis (OA) and Alzheimer's disease (AD) are common conditions in older adults over the age of 60.
In recent years, it has been found that osteoarthritis increases the risk of Alzheimer's disease in older adults [1,2]. However, the reasons behind this are still poorly understood.
Recently, a research team led by Tengfei Guo from the Institute of Biomedical Engineering, Shenzhen Bay Laboratory, published an important research result in Neurology, a leading journal in the field of neurology [3], revealing the potential reasons behind.
Based on imaging, case and APOE genotype data from 374 Aβ-PET-positive subjects, they found for the first time that osteoarthritis is associated with accelerated cortical Aβ aggregation and high levels of Aβ-associated tau deposition in the primary motor area (precentral gyrus) and somatosensory area (postcentral gyrus) of the brain [3]. This finding provides imaging evidence that osteoarthritis increases the risk of Alzheimer's disease in older adults.
Jing Du and Anqi Li from the Institute of Biomedical Engineering, Shenzhen Bay Laboratory, and Era from the Center of Neurology, the Seventh Hospital of Sun Yat-sen University, are the co-first authors of the research paper.
Tengfei Guo's team retrieved data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort of 374 Aβ-PET-positive subjects. Of these 374 subjects, 114 had normal cognition (CU), 212 had confirmed mild cognitive impairment (MCI), and 48 had confirmed Alzheimer's disease-associated dementia.
All subjects had longitudinal Aβ-PET imaging data (defined by FBP SUVR, median follow-up 3.3 years), documented history of osteoarthritis, and APOE-ε4 genotyping information. 235 (62.8%) were APOE-ε4 carriers, 184 (49.2%) were female, and 119 (31.8%) had a confirmed diagnosis of osteoarthritis. In addition, 97 subjects (38 CU, 58 MCI, and 1 Alzheimer's disease-associated dementia) had a follow-up FTP PET scan (to detect tau) 5.4 years (median) after baseline FBP PET.
Subsequently, the researchers divided all patients into two groups: OA+ and OA-, based on a history of confirmed osteoarthritis as the grouping basis. Overall, there were no significant differences between the OA+ and OA- groups in terms of age, education, baseline FBP SUVR (precentral and postcentral gyrus), percentage of females, APOE-ε4 carriage, and cognitive status.
Baseline Characteristics of Subjects in Both Groups
At baseline, females and cognitive impairment were associated with higher baseline FBP SUVR in precentral gyrus and postcentral gyrus cortex. In contrast, both osteoarthritis and APOE-ε4 alleles were not associated with baseline FBP SUVR in precentral gyrus and postcentral gyrus cortex.
Longitudinally, subjects in the OA+ group had significantly faster Aβ aggregation in the precentral gyrus and postcentral gyrus cortex compared to subjects in the OA- group. However, APOE-ε4 had no independent effect on Aβ aggregation in precentral and postcentral gyrus cortex and no interaction with OA. Other factors were also not significantly correlated with longitudinal Aβ aggregation.
In 96 participants with FTP tau-PET data measured 5.4 years (median) after baseline Aβ-PET, osteoarthritis was associated with higher FTP SUVR in the precentral gyrus and postcentral gyrus cortex. This phenomenon suggests that osteoarthritis also promotes tau protein deposition. apoE-ε4, although not independently imaging tau, strengthens the correlation between osteoarthritis and tau deposition.
Specifically, in 53 APOE-ε4 carriers, osteoarthritis was associated with higher tau deposition in the precentral gyrus and postcentral gyrus cortex. In the 43 APOE-ε4 non-carriers, no significant differences in tau deposition were found between the OA+ and OA- groups.
The relationship between osteoarthritis and tau deposition and the effect of APOE-ε4 on the relationship between the two
Tengfei Guo's team also found that higher baseline Aβ-PET and osteoarthritis were independently and interactively related to tau deposition in precentral and postcentral gyrus cortex.
Overall, this study shows that osteoarthritis promotes Aβ aggregation and tau deposition in precentral and postcentral gyrus cortex, while APOE-ε4 does not affect the progression of these two Alzheimer's disease pathologies in precentral and postcentral gyrus cortex.
This finding provides insight into the fact that osteoarthritis increases Alzheimer's disease in the elderly and raises the importance of chronic disease management in the elderly for Alzheimer's disease prevention.
