Neurology: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) reveals associations between lymphatic function and neuropsychology, gray matter volume, sleep: Sleep health has implications for brain health

The discovery of the lymphatic system provides a new perspective for studying brain protein homeostasis and a promising target for the prevention and treatment       of neurodegenerative diseases
.
This highly organized fluid transport system includes the inflow of cerebrospinal fluid (CSF) along the perivascular space (PVS) and facilitated transfer to the brain interstitium by the water channel 4 (AQP4) water channel
.
The CSF-interstitial fluid is then directed to the venous PVS, which ultimately results in fluid flow within the brain parenchyma, which removes metabolic waste products
.

      Experiments in rodents have provided considerable insight into lymphatic physiology, particularly with regard to the relationship between sleep and the lymphatic system
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Growing evidence suggests that non-rapid eye movement (NREM) sleep potently promotes lymphatic fluid transport, whereas it is inhibited during wakefulness
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Radionuclide tracing studies showed that anesthetized or naturally sleeping mice had a 90 percent increase in lymphatic inflow compared to awake mice, which in turn enhanced the clearance of amyloid beta and tau proteins from their brains
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In both rodent and human studies, sleep disturbances accelerate amyloid beta deposition, which is seen in Alzheimer's disease (AD)
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These results suggest that lymphatic dysfunction may be used to explain the link between sleep disturbance and AD pathology
.

      Although a great deal of knowledge has been gained from animal studies, further research is necessary to confirm whether findings about the animal's lymphatic system are applicable to humans
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Small-scale studies in humans echo findings in rodents to some extent, but the invasiveness of current assessment tools, such as intrathecal injection of contrast agents, limits comprehensive studies of the lymphatic system in humans
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Diffusion magnetic resonance imaging (MRI) has emerged as a non-invasive tool to assess the human lymphatic system
.
Taoka et al.
proposed a measure of lymphatic flow, called the Diffusion Tensor Imaging Analysis Along Perivascular Space (DTI-ALPS) index , and found that changes correlated with Mini Mental Status Examination (MMSE) scores in AD patients , is considered to reflect the indicators of lymphatic dysfunction
.

      DTI-Alps presents an opportunity for non-invasive studies of the human lymphatic system, using this method to assess the lymphatic system in a community-based non-demented elderly population with the aim of correlating lymphatic function with sleep, neuropsychological performance, and gray matter volume connection between
.

      This cross-sectional study included individuals 60 years of age or older who participated in a study integrating geriatric system data to explore solutions for healthy aging between September 2019 and October 2020
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Seniors living in the community are registered at two different locations
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Participants with dementia, major depressive disorder and other major organ system abnormalities were excluded
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Sleep profiles were obtained using questionnaires and polysomnography
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Implemented neuropsychological test portfolios include Cognitive Everyday (ECOG) and the Establishment of the Neuropsychological Portfolio Registry for Alzheimer's Disease (CERAD-NB) Consortium
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Gray matter volume was estimated from magnetic resonance imaging (MRI)
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Diffusion tensor imaging along the perivascular space (DTI-Alps) index was used as an MRI marker of lymphatic function
.

• A total of 84 participants (mean age 73.
  3 [7.
  1] years, 47 women [56.
  0%]) were analyzed
  .
  
• Multivariate linear regression analysis revealed age (unstandardized beta, -0.
  0025 [SE, 0.
  0001]; P=0.
  02), N2 sleep time (unstandardized beta, 0.
  0002 [SE, 0.
  0001]; P=0.
  04) and apnea-hypopnea index (unnormalized beta, -0.
  0011 [SE, 0.
  0005]; P=0.
  03) was independently associated with DTI-ALPS
  .
  
• Higher DTI-ALPS was associated with better ECOG language scores (unnormalized β, -0.
  59 [SE, 0.
  28]; P=0.
  04) and better CERAD-NB vocabulary learning delayed recall subtest scores ( unnormalized β, 0.
  28) 6.
  17 [SE, 2.
  31]; P=0.
  009)
  .
  
• Higher DTI-ALPS was also associated with higher gray matter volume after controlling for age, sex, and total intracranial volume (unnormalized beta, 107.
  00 [SE, 43.
  65]; P=0.
  02)
  .
  

      The study identified a significant association between lymphatic function and sleep, underscoring the importance of sleep for brain health
.
Associations between DTI-Alps and neuropsychological performance and cerebral gray matter volume were also revealed, suggesting that DTI-Alps have the potential to be a biomarker of cognitive impairment
.

Source: Siow TY, Toh CH, Hsu JL, Liu GH, Lee SH, Chen NH, Fu CJ, Castillo M, Fang JT.
Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults .
Neurology.
2021 Dec 14:10.
1212/WNL.
0000000000013215.
doi: 10.
1212/WNL.
0000000000013215.
Epub ahead of print.
PMID: 34906982.