Nassir, Che Mohd Nasril Che Mohd
(2018)
Exploratory longitudinal studies on cerebral small vessel disease (CSVD) in apparently asymptomatic individuals with neuropsychological, neuroimaging and microparticles profiling.
Masters thesis, Universiti Sains Malaysia.
Abstract
The prevalence of cerebral small vessel disease (CSVD) for asymptomatic (‘silent’)
manifestation is typically obtained from incidental findings of white matter
hyperintensities (WMHs) on magnetic resonance imaging (MRI). This study aimed to
explore novel surrogate markers for the assessment of white matter integrity in CSVD
among apparently asymptomatic individuals with neuropsychological, neuroimaging
and microparticles (MPs) profiling. The recruited subjects with low to moderate
cardiovascular risk prediction score as defined by QRISK2 underwent MRI brain scan,
followed by neuropsychological indices of Weschler Adults Intelligence Scale
(WAIS-IV) that measured their perceptual reasoning (PRI), working memory (WMI)
and processing speed (PSI). Prior to flow cytometry MPs subpopulations
enumerations, 18 ml of fasting blood was collected. Similar procedures were carried
out at baseline (T0) and at 12 months follow-up (T12). At baseline, 48 asymptomatic
individuals were recruited (mean age: 38.81±10.9); 24 were young adults, YA (mean
age 29.7±4.33) and 24 mature adults, MA (mean age: 47.92±7.01). Fifteen (29.4%)
had WMHs (WMH+) detected, of who five were YA, and 10 were MA. However, after
one-year, 40 (mean age: 39.35±11.31) were able to participate; eight (20%) subjects
were lost to follow up fourteen (35%) subjects were WMH+ and 26 (65%) were WMHAge influenced the presence of WMHs and WMH+ subject as having higher risk of
CSVD. WMH+ subjects showed higher mean percentage of QRISK2 and MPs
especially platelet derived MPs (CD41a and CD62P). In term of white matter integrity,
QRISK2 score increased with reduced integrity (measured by fractional anisotropy,
FA) of white matter tracts of superior corona radiata (SCR) and superior longitudinal
fasciculus (SLF). White matter integrity was also reduced with advancing age. The
PRI and WMI performance varied between subjects, but PSI consistently lower in
WMH+ subjects. There were no significant temporal changes on cognitive and
memories performances from both groups. FA of all tracts consistently and positively
correlated with neuropsychological profiles. The integrity of white matter tracts such
as left SLF and left anterior corona radiata were correlated with red blood cell MPs
(CD235a) (r= -0.313, p=0.030) and CD62P (r=0.289, p= 0.047), respectively.
Although with a relatively small sample size and one-year follow-up period, this study
had established the correlations between cardio-cerebrovascular risk prediction by
QRISK, neuropsychological indices performance, WMHs/white matter integrity from
diffusion MRI and MPs profiling as potential surrogate markers for CSVD in
apparently asymptomatic individuals.
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