Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease

Sep 19, 2022Neurology

Links Between Brain Waste Clearance, Amyloid Build-Up, and Thinking Skills in Mild Cognitive Impairment and Alzheimer’s Disease

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Abstract

Patients with Alzheimer’s disease (AD) had significantly higher perivascular space volume fraction and free water volume in white matter than healthy controls.

Patients with AD exhibited significantly higher total, white matter, and basal ganglia perivascular space volume fraction compared to healthy controls.
Mild cognitive impairment (MCI) patients showed increased total and white matter perivascular space volume fraction, but not to the same extent as those with AD.
A lower index of diffusivity along the perivascular space was observed in AD patients compared to healthy controls.
Low index of diffusivity was associated with lower levels of cerebrospinal fluid Aβ42 and worse cognitive performance.
High free water volume in white matter correlated with lower cerebrospinal fluid Aβ42 and poorer cognitive abilities.

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BACKGROUND AND OBJECTIVES: The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid β (Aβ) accumulation. However, its involvement in Alzheimer disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aβ deposition.

METHODS: MRI measures, including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer's Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD. Statistical analyses were performed with age, sex, years of education, andstatus as confounding factors. APOE

RESULTS: In total, 36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia PVSVF (Cohen= 1.15-1.48;< 0.001) and FW-WM (Cohen= 0.73;< 0.05) and a lower ALPS index (Cohen= 0.63;< 0.05) than healthy controls. Meanwhile, the MCI group only showed significantly higher total (Cohen= 0.99;< 0.05) and WM (Cohen= 0.91;< 0.05) PVSVF. Low ALPS index was associated with lower CSF Aβ42 (= 0.41,= 0.026), FDG-PET uptake (= 0.54,< 0.001), and worse multiple cognitive domain deficits. High FW-WM was also associated with lower CSF Aβ42 (= -0.47,= 0.021) and worse cognitive performances. d p d p d p d p d p r p r p r p s fdr s fdr s fdr

DISCUSSION: Our study indicates that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. We also report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.

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Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease

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