Glymphatic System Dysfunction as a Predictor of Cognitive Decline and Incident Dementia
Chengqian Li1, Wenxin Li1, Zi-Yue Liu1, Fei-Fei Zhai1, Fei Han1, Lixin Zhou1, Jun Ni1, Ming Yao1, Yi-Cheng Zhu1
1Department of Neurology, Peking Union Medical College Hospital
Objective:
This study aims to explore whether the baseline diffusion along the perivascular space (ALPS) index could predict cognitive decline and incident dementia in a community-based population.
Background:
Previous studies reported that the ALPS index and brain parenchymal injury were associated with cognitive decline and incident dementia in aging populations, while the longitudinal study remains limited.
Design/Methods:
A total of 973 dementia-free participants from the Shunyi Study (mean age, 57 years; 37% men) underwent magnetic resonance imaging between 2013 and 2016 to quantify the ALPS index. Linear mixed models were used to evaluate the longitudinal associations between the ALPS index and cognitive decline across multiple cognitive domains. Cox proportional hazard models were used to explore the association between this index and incident dementia. Mediation analyses were conducted to explore the potential mediating effects of brain parenchymal injury on the relationship between the ALPS index and cognition.
Results:
The baseline ALPS index predicted longitudinal changes in global cognition (Montreal Cognitive Assessment, β=0.070, P=0.010), language (verbal fluency test, β=0.081, P=0.008), visuospatial perception (block design subtest of Wechsler intelligence scale, β=0.082, P=0.010), and executive function (Trail Making Test, β=-0.116, P<0.001). A lower ALPS index was significantly associated with a higher risk of incident dementia (HR=0.666, P=0.033). Mediation analysis revealed that fractional anisotropy mediated the associations between the ALPS index and executive function (mediation effect: 21.9%) and visuospatial perception (mediation effect: 68.8%). The white matter hyperintensity fraction mediated the association between this index and global cognition (mediation effect: 55.0%).
Conclusions:
This longitudinal evidence supports the association between the ALPS index and cognitive decline. Furthermore, subcortical parenchymal injury mediates the relationship between this index and cognitive function.
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