Loss of Glymphatic Drainage of Cerebrospinal Fluid Correlates with Alzheimer's Disease Progression
A magnetic resonance imaging (MRI) approach known as diffusion tensor image analysis along the perivascular space (DTI-ALPS) can be used to measure the flow of cerebrospinal fluid leaving the brain via the glymphatic system, a network of vessels that parallels blood vessels passing out of the brain. This drainage of cerebrospinal fluid allows metabolic waste to leave the brain, but becomes progressively ever more impaired with advancing age. It is thought that this loss of drainage leads to a build up of protein aggregates such as misfolded amyloid-β that contribute to the onset and progression of neurodegenerative conditions. Here researchers review the evidence for a reduced drainage rate measured via DTI-ALPS to correlate with established measures of the progression of Alzheimer's disease. One might recall that some animal studies have shown that forcing an increase in glymphatic flow of cerebrospinal fluid has produced a reduction in neurodegenerative pathology.
Although the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is widely utilized as a proxy for glymphatic function in Alzheimer's Disease (AD) research, its association with core AD pathological biomarkers remains inconclusive due to inter-study heterogeneity. This systematic review aimed to investigate associations between the DTI-ALPS index and AD biomarkers and to elucidate potential sources of heterogeneity.
Thirty-six studies were included. Meta-analyses revealed significant correlations between the DTI-ALPS index (N = 22) and amyloid-β positron emission tomography (PET) deposition (N = 9), Mini-Mental State Examination (MMSE) (N = 15), and Montreal Cognitive Assessment (MoCA) (N = 10) scores. Conversely, the association with tau PET deposition (N = 3) was not significant after adjusting for publication bias. Regarding clinical staging, indices were significantly lower in AD and mild cognitive impairment groups compared to controls but no difference was found between the two patient groups. Based on meta-regression and narrative synthesis results, we identified methodological variability and AD pathological complexity as primary sources of heterogeneity.