Neurocognitive profiles and thrombogenic inhibitors (TAFI, TFPI) in apparently asympomatic individuals with cerebral small vessel disease
Cerebral small vessel disease (CSVD) is the term coined to address the many abnormal presentations of the brain under neuroimaging techniques. White matter hyperintensities (WMH), one of the most common appearance seen under normal healthy populations which often described as normal appearing whi...
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| 主要作者: | |
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| 格式: | Thesis |
| 语言: | English |
| 出版: |
2018
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| 主题: | |
| 在线阅读: | http://eprints.usm.my/56783/1/Dr.%20Zakiyyah%20Munirah%20Mohd%20Zaki-24%20pages.pdf |
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| 总结: | Cerebral small vessel disease (CSVD) is the term coined to address the many
abnormal presentations of the brain under neuroimaging techniques. White matter
hyperintensities (WMH), one of the most common appearance seen under normal
healthy populations which often described as normal appearing white matter
becomes a concern as it posed a detrimental effect on cognitive functions as well as
gait and motor abilities, culminating a huge burden to the society economically.
There are various causal factors suggested to contribute in pathogenesis of this silent
yet progressive disease. Among the main pathways hypothesized are the
coagulation/complement, inflammation, signal transduction and lipid metabolism.
This current study aims to determine the relationship between CSVD in healthy
individuals, and the selected blood biomarkers particularly thrombogenic inhibitors
(TAFI and TFPI) as well as neurocognitive profiles. This was an exploratory study
from random selection of subjects recruited from Klinik Rawatan Keluarga, Hospital
Universiti Sains Malaysia. An online-based cardiovascular risk calculator (QRISK2)
was also used for risk prediction. Those who met the inclusion and exclusion criteria
were recruited and underwent MRI brain scanning (Phillips 3-Tesla Achieva MR
Scanner), blood sampling and neuropsychological performance based on Wechsler
Adult Intelligent Scale IV (WAIS-IV). The baseline MRI images were used to group
the subjects based on the presence of white matter hyperintensities (WMHs) scored by Fazekas scale. Blood plasma was used to determine the thrombogenic factors
(TAFI, TFPI) by using ELISA and seven subtests of WAIS IV were taken for
neuropsychological testing Block Design, Matrix Reasoning and Visual Puzzle; Digit
Span and Letter-Number Sequencing; Coding and Symbol Search for three different
main cognitive domains Perceptual Reasoning, Working Memory and Processing
Speed, respectively. The analyses were done by performing statistical test using IBM
SPSS Statistics version 24.0. A total of thirty-three (N=33) subjects recruited with
QRISK2 score <20%, aged between 25 to 62 years old, with similar distribution of
30% male and 70% female at both baseline and follow up. Upon MRI scanning, 15
(45.5%) were detected with WMH at baseline however only 11 (40.7%) of them
came back for follow up at one-year. The mean age was 39 years old (range from 25
to 62 year old. TFPI at follow up was seen to be significantly increased meanwhile
TAFI was higher at baseline point. However, only TFPI at follow up contributed to
the association model of WMH outcome [B=-3.964, Wald 5.106, OR= 0.021,
p<0.05]. Comparing both groups together, only TFPI showed significant changes
between WMH+ and WMH- at follow up. The neurocognitive profiling shows
association between PSI with age, QRISK2 score and PRI with p value 0.003, 0.016
and 0.018 respectively, however no cognitive domains show any association or
predictive value to the WMH outcome. Interestingly, WMI and TFPI at follow up
show a significant correlation with p<0.05. The result suggests that only TFPI is
associated with presence of WMH, coupled with changes in PSI. As for TAFI,
despite a decreased level within a year, its role is probably not apparent in the early
stage of CSVD. Finally, the study has also established a selected cohort of at-risk
asymptomatic CSVD individuals within our local population for future studies,
including to further elucidate the role of emerging or novel biomarkers for CSVD. |
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