Generalized osteoporosis but not axial osteopenia is associated with cognitive impairment in Parkinson’s disease

BACKGROUND: Bone and brain interact bidirectionally through the brain-bone axis. However, the relationship between bone mineral density (BMD) and cognitive impairment in Parkinson's disease (PD) remains unclear. METHODS: We screened and enrolled 120 PD patients, measuring BMD at the bilateral neck of femur, total hip, one-third distal radius and lumbar spine while assessing various clinical symptoms. Latent class analysis (LCA) was employed for BMD classification, followed by statistical analyses to assess their associations with cognitive impairment. RESULTS: Patients with cognitive impairment exhibited generally reduced BMD in the measured skeletal locations compared to those without cognitive impairment, while serum biochemical markers did not show this trend. LCA by utilizing multiple regional BMD measurements classified patients into two distinct clusters: axial osteopenia and generalized osteoporosis. Cognitive impairment was more pronounced in the generalized osteoporosis cluster. Further analysis showed that PD patients in the generalized osteoporosis cluster had an increased risk of cognitive impairment (adjusted odds ratio: 9.02, 95% confidence interval: 2.68-35.40). After stratification, this association was more prominent in older or male patients, in those whose non-dominant hand side exhibited more severe motor symptoms, and in patients with either a longer disease duration or the non-tremor dominant subtype. CONCLUSIONS: This study demonstrates for the first time that generalized osteoporosis, rather than axial osteopenia, is associated with cognitive impairment in PD. Interventions aimed at mitigating generalized BMD decline could be a potential therapeutic approach to improve cognitive function in PD patients.