The present study revealed that hypertension is the major vascular risk of WMHs while other common vascular risk factors including diabetes, dyslipidemia, obesity, smoking, and heart disease showed non-significant relation with WMHs severity. At the same time, the results did not identify the effect of advanced age on WMHs progression possibly due to the selection criteria of a specific age (young-old geriatric subjects). These results are agreeing with Croall and colleagues, 2018 [17] as well as Wardlaw and colleagues, 2019 [3] who stated that hypertension is a major risk of WMHs, yet the disorder is highly heterogenous and multi-etiological where heritable factors play a major role in its pathogenesis. On the other hand, Yu and colleagues, 2018 [18] as well as Walsh and colleagues, 2019 [19] found significant associations between the existence of type 2 DM as well as obesity and WMHs progression possibly due to inclusion of patients with metabolic syndrome and clinically evident strokes rather than subjects with accidentally discovered asymptomatic WMHs.
The results of this work identified lower cognitive performance, more depressive symptoms (feeling of sadness, helplessness, and hopelessness) as well as reduced activity of daily livings (ADLs) in WMHs subjects. These data are going with the study of Madden and colleagues, 2017 [20] who hypothesized that WMHs are neither silent nor innocent but brain resilience may delay their clinical implications by undergoing several neuro-modulatory processes including reduction in the cost of wiring, reorganization of the resting-state and default mode networks as well as paradoxical functional hyper-connectivity.
The study showed that the MoCA scale at 26 points had 58% sensitivity and 70% specificity for the diagnosis of cognitive impairments associating WMHs (Fig. 5). This low sensitivity and specificity indicate that the MoCA scale is not suitable for the evaluation of the subtler cognitive impairments associating with WMHs (Fig. 4). This result is parallel with that of Abd Ghafar and colleagues, 2019 [21] who declared that global cognitive assessment scales including MoCA could be a sensitive screening test for patients with vascular cognitive impairment yet this sensitivity is much lowered in preclinical cases with subjective cognitive decline including occult WMHs subjects.
Neurocognitive assessment of WMHs subjects revealed marked affection of attention and executive functions while language vocabulary and memory were little impaired. These results are in harmony with that of Rensma and colleagues, 2018 [22] as well as Bahnasy and colleagues, 2018 [23] who concluded that subjects with extensive WMHs showed subnormal executive functions (information processing speed, set shift, and multitasking) and reduced capacity for sustained attention with relative sparing of episodic memory and delayed recall. On the other hand, they identified significant language dysfunctions in their studied subjects which is not compatible with our results possibly due to different study design and inclusion of clinically symptomatic stroke and mild cognitive impairment patients.
The results of the present study showed non-significant differences between WMHs and non-WMHs subjects regarding the BBT which is in harmony with the work of Shen and colleagues, 2016 [24] who concluded that BBT is an insensitive biomarker for increased risks of falls in subjects with WMHs.
The results of the present work showed impaired static and dynamic balance control in WMHs subjects evidenced by decreased VIS and VEST ratios which were negatively correlated with WMHs disease burden. These results are in harmony with that of Shen and colleagues, 2016 [24] as well as Moscufo and colleagues, 2018 [25] who concluded that WMHs are at increased risk of falls due to associated balance and gait dysfunctions. They attributed these mobility impairments to the subtle white matter microstructural abnormalities, particularly in the corpus callosum.
The study revealed reduction of FA in each of CST, TCC, and arcuate fasciculi of WMHs subjects with preserved tracts, densities pointing to the microstructural connectivity changes induced by WMHs. At the same time, there was an observable increased heterogenicity of axon FA (myelination) in the studied tracts denoting decreased synchrony of impulses transduction. These results are passing with that of Loos and colleagues, 2018 [26] as well as Tuladhar and colleague, 2016 [27] who stated that WMHs is a dynamic whole-brain disorder resulting in disruption of the axons not only in the WMHs lesions but also in their normally appearing white matter penumbra. The net results are dying back of the neuronal cell bodies and disruption of brain network integrity progressing to disconnection syndrome.
A potentially important observation is the little affection of the inferior longitudinal fasciculi than other studied white matter tracts which signifies that brain areas have different susceptibilities to WMHs induced changes. These data may open a small window in a better understanding of the pathogenesis of WMHs with the consecutive introduction of more specific treating agents. These results are following the work of Frey and colleagues, 2019 [28] as well as Vangberg and colleagues, 2019 [29] who identified that certain brain regions particularly those with the aberrant structure are more vulnerable to the microstructural compromise induced by WMHs lesions possibly due to different vulnerability to the induced ischemia and neuroinflammation.
