This work was supported by matching and donation funds (Cerebrovascular Research Fund, SHAC Matching Grant, UGC Matching Grant, and Dr. William Mong Research Fund in Neurology awarded to Professor R.T.F. Cheung).

The study protocol was approved by the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB) for human research.
1. Participants
<ol>
	<li>Recruit otherwise healthy elderly Chinese subjects (from 65 to 99 years old, mean age 72) with a history of hypertension for at least 5 years.</li>
	<li>Exclude participants with any disease affecting the cognitive function and/or with any disability hindering the completion of the required ...

<ol>
	<li>Jokinen, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incident+lacunes+influence+cognitive+decline:+the+LADIS+study.">Incident lacunes influence cognitive decline: the LADIS study.</a> Neurology. 76 (22), 1872-1878 (2011).</li><li>Lawrence, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+decline+in+structural+networks+predicts+dementia+in+cerebral+small+vessel+disease.">Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease.</a> Neurology. 90 (21), e1898-e1910 (2018).</li><li>Chen, Y. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atrophy+of+the+left+dorsolateral+prefrontal+cortex+is+associated+with+poor+performance+in+verbal+fluency+in+elderly+poststroke+women.">Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women.</a> Neural Regeneration Research. 8 (4), 346-356 (2013).</li><li>Dufouil, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Severe+cerebral+white+matter+hyperintensities+predict+severe+cognitive+decline+in+patients+with+cerebrovascular+disease+history.">Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history.</a> Stroke. 40 (6), 2219-2221 (2009).</li><li>Mungas, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+volumetric+MRI+change+and+rate+of+cognitive+decline.">Longitudinal volumetric MRI change and rate of cognitive decline.</a> Neurology. 65 (4), 565-571 (2005).</li><li>Benjamin, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lacunar+Infarcts,+but+Not+Perivascular+Spaces,+Are+Predictors+of+Cognitive+Decline+in+Cerebral+Small-Vessel+Disease.">Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease.</a> Stroke. 49 (3), 586-593 (2018).</li><li>Carey, C. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subcortical+lacunes+are+associated+with+executive+dysfunction+in+cognitively+normal+elderly.">Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly.</a> Stroke. 39 (2), 397-402 (2008).</li><li>Zi, W., Duan, D., Zheng, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairments+associated+with+periventricular+white+matter+hyperintensities+are+mediated+by+cortical+atrophy.">Cognitive impairments associated with periventricular white matter hyperintensities are mediated by cortical atrophy.</a> Acta Neurologica Scandinavica. 130 (3), 178-187 (2014).</li><li>Vernooij, M. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=White+Matter+microstructural+integrity+and+cognitive+function+in+a+general+elderly+population.">White Matter microstructural integrity and cognitive function in a general elderly population.</a> Archives of General Psychiatry. 66 (5), 545-553 (2009).</li><li>Blackburn, H. L., Benton, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revised+administration+and+scoring+of+the+digit+span+test.">Revised administration and scoring of the digit span test.</a> Journal of Consulting and Clinical Psychology. 21 (2), 139-143 (1957).</li><li>Hachinski, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=National+Institute+of+Neurological+Disorders+and+Stroke-Canadian+Stroke+Network+vascular+cognitive+impairment+harmonization+standards.">National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards.</a> Stroke. 37 (9), 2220-2241 (2006).</li><li>Wong, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Validity,+Reliability+and+Utility+of+the+Cantonese+Montreal+Cognitive+Assessment+(MoCA)+in+Chinese+Patients+with+Confluent+White+Matter+Lesions.">The Validity, Reliability and Utility of the Cantonese Montreal Cognitive Assessment (MoCA) in Chinese Patients with Confluent White Matter Lesions.</a> Hong Kong Medical Journal. 14 (6), (2008).</li><li>Lee, T. M., Chan, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stroop+interference+in+Chinese+and+English.">Stroop interference in Chinese and English.</a> Journal of Clinical and Experimental Neuropsychology. 22 (4), 465-471 (2000).</li><li>Gawryluk, J. R., Mazerolle, E. L., Beyea, S. D., D'Arcy, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MRI+activation+in+white+matter+during+the+Symbol+Digit+Modalities+Test.">Functional MRI activation in white matter during the Symbol Digit Modalities Test.</a> Frontiers in Human Neuroscience. 8, 589 (2014).</li><li>Chiu, H. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+modified+Fuld+Verbal+Fluency+Test:+a+validation+study+in+Hong+Kong.">The modified Fuld Verbal Fluency Test: a validation study in Hong Kong.</a> The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences. 52 (5), P247-P250 (1997).</li><li>Cordonnier, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=improving+interrater+agreement+about+brain+microbleeds:+development+of+the+Brain+Observer+MicroBleed+Scale+(BOMBS).">improving interrater agreement about brain microbleeds: development of the Brain Observer MicroBleed Scale (BOMBS).</a> Stroke. 40 (1), 94-99 (2009).</li><li>Poels, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+microbleeds+are+associated+with+worse+cognitive+function:+the+Rotterdam+Scan+Study.">Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study.</a> Neurology. 78 (5), 326-333 (2012).</li><li>Yamashiro, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+microbleeds+are+associated+with+worse+cognitive+function+in+the+nondemented+elderly+with+small+vessel+disease.">Cerebral microbleeds are associated with worse cognitive function in the nondemented elderly with small vessel disease.</a> Cerebrovascular Diseases Extra. 4 (3), 212-220 (2014).</li><li>Fazekas, F., Chawluk, J. B., Alavi, A., Hurtig, H. I., Zimmerman, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+signal+abnormalities+at+1.5+T+in+Alzheimer's+dementia+and+normal+aging.">MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging.</a> American Journal of Roentgenology. 149 (2), 351-356 (1987).</li><li>Zhang, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+profiles+of+cognitive+impairment+associated+with+different+silent+cerebrovascular+lesions+in+hypertensive+elderly+Chinese.">Distinct profiles of cognitive impairment associated with different silent cerebrovascular lesions in hypertensive elderly Chinese.</a> Journal of the Neurological Sciences. 403, 139-145 (2019).</li><li>Arboix, A., Roig, H., Rossich, R., Martinez, E. M., Garcia-Eroles, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+between+hypertensive+and+non-hypertensive+ischemic+stroke.">Differences between hypertensive and non-hypertensive ischemic stroke.</a> European Journal of Neurology. 11 (10), 687-692 (2004).</li><li>Grau-Olivares, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progressive+gray+matter+atrophy+in+lacunar+patients+with+vascular+mild+cognitive+impairment.">Progressive gray matter atrophy in lacunar patients with vascular mild cognitive impairment.</a> Search Results. 30 (2), 157-166 (2010).</li></ol>

In the study, we have combined the results of a battery of neuropsychological assessment and findings of a multi-sequence MRI examination to evaluate the impact of different types of SCLs on various cognitive functions. The major types of SCLs were examined (i.e., CMBs, SLs and WMHs). As previous studies have revealed that SCLs in different locations may represent different pathology and lead to different consequences, we categorized CMBs and SLs into strictly lobar (i.e., lobar only without deep ones) and deep ones (wit...

Silent lacunes (SLs), cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) are referred to as silent cerebrovascular lesions (SCLs). Two types of WMHs are recognized: periventricular WMHs (PVHs) and deep WMHs (DWMHs). SCLs were once regarded as benign lesions without clinical significance. After decades of research, SCLs are now confirmed to be linked to varying functional impairment and cognitive deficits1,2. Nevertheless, consistent evidence is still limited in the spectrum and magnitude of cognitive effects of different types of SCLs. Moreover, the underlying mechanisms are elusive.
Most previous studies either recruited hospital patients with severe medical conditions3,4,5 or included participants with advanced cerebral small vessel diseases6,7. The heterogeneity of the participants among different studies has partly contributed to the inconsistent results. To exclude these confounding factors, we conducted the current one-centered&#160;study as an attempt to provide a clear picture through assessment of a relatively large, pure cohort recruited from a primary care setting. Furthermore, previous studies have predominantly focused on one or two types of SCLs and did not fully evaluate the independent associations between individual SCLs and specific cognitive functions. Therefore, we assessed various types of SCLs in the current study.
Neuropsychological tests are widely used to assess cognitive function of specific domains. They are useful in differentiation between normal aging and early cognitive impairment. Results of properly conducted neuropsychological assessment are sensitive in discerning behavioral and functional deficits. A battery of structured neuropsychological tests was chosen, including forward and backward digit span tests, symbol digit modalities test (SDMT), Stroop test, verbal fluency test and Montreal Cognitive Assessment (MoCA). Scores from these tests were grouped and combined to represent performance in different cognitive domains8,9. Such a method is widely used and is time efficient. A major drawback is that different neuropsychological tests may partly overlap in their tested domains. A more specific alternative is to use computer-based assessment with well-designed modules constructed using the E-Prime system, which is time-consuming and may not be suitable for screening purposes.
In conclusion, we aimed to assess the associations between the burden of different SCLs and impairment of various cognitive domains. Furthermore, vascular risk factors and other types of SCLs were controlled for to determine the distinct and independent profile&#160;of cognitive impairment of each type of SCLs.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T MRI</td>
			<td>Philips Medical Systems</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluation of the cognitive performance of hypertensive patients with silent cerebrovascular lesions

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to cognitive decline in the elderly. However, the distinct effects of each type of the lesions on cognitive performance remain unclear. Moreover, research data from Chinese elderly with SCLs is scarce. In this study, 398 otherwise healthy hypertensive elderly subjects (median age 72 years) were included and assessed. All participates were required to complete a battery of structured neuropsychological assessment, including forward and backward digit span tests, symbol digit modalities test, Stroop test, verbal fluency test and Montreal Cognitive Assessment. These tests were used to assess attention, executive function, information processing speed, language, memory and visuospatial function. A multi-sequence 3T MRI scanning was arranged within one month of the neuropsychological assessment to evaluate the burden of SCLs. SCLs were rated visually. Cerebral microbleeds (CMBs) and silent lacunes (SLs) were identified as strictly lobar CMBs and SLs or deep CMBs and SLs according to their locations, respectively. Similarly, white matter hyperintensities (WMHs) were separated into periventricular WMHs (PVHs) and deep WMHs (DWMHs). A series of linear regression models were used to assess the correlation between each type of SCLs and individual cognitive function domain. The results showed that CMBs tend to impair language-related cognition. Deep SLs affect executive function, but this association disappeared after controlling for other types of SCLs. PVHs, rather than DWMHs, are associated with cognitive decline, especially in executive function and processing speed. It is concluded that different aspects of SCLs have differential impact on cognitive performance in hypertensive elderly Chinese.

The mean age of the 398 participants was 72.0 (from 65 to 99, SD = 5.1) years, and there were 213 men (53. 5%; Table 3). Table 4 summarizes the neuropsychological assessment results. Only 5 participants had all four types of SCLs. One or more types of SCLs were found in 169 (42.5%) participants, and 35 (8.8%) and 17 (4.3%) participants had 2 and 3 types of SCLs, respectively (Table 5).
<p class="jove_content" fo:keep-together.within-p...

Watch this Scientific Journal Video about Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions at JoVE.com

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

Here, we present a protocol to assess whether various types of silent cerebrovascular lesions are differentially associated with deficits in certain cognitive domains in a cohort of 398 hypertensive elderly Chinese, using a combination of neuropsychological tests and multi-sequence 3T MRI scanning.

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to ...

Silent cerebrovascular lesions can cause various functional impairments and cognitive deficits. However, the distinct effects of different types of lesions on cognitive performance remain unclear. Using both neuro-psychological tests and multi-sequence MRI scans, we can assess whether various types of cerebrovascular lesions are differentially associated with deficits in specific cognitive domains.Demonstrating the study procedures will be done by Junling Gao, my research officer, and Tracy Lam, my technical officer. To set up a symbol digit modalities test, pair one to nine digits in numeric order with nine unassociated symbols. A battery of structured neuro-psychological tests were administered, and two of them were chosen for demonstration.Before starting the test, instruct the participant to fill in the blank with the correctly paired digit below each symbol. Allow the participant to fill in the first 10 blanks as practice, pointing out any errors during the practice stage, and encouraging the participant to be correct. When the participant is ready, start the test, encouraging the participant to fill in the blanks as quickly and accurately as possible in 90 seconds.When the participant has finished or the time has run out, record the number of correct responses and restart the test, this time having the participant provide the correctly pair digits verbally. To assess verbal fluency, ask the participant to verbally provide a list of names belonging to each of two categories for one minute per category. Then record the total number of names listed for each category.To perform visual ratings of the lesions, first import the data into an appropriate medical imaging software program, and use the Anonymize button to anonymize the participants'information. To rate visual silent cerebrovascular lesions, first locate the silent lacunes and T1 weighted horizontal images in which the lesions appear as hypointense two to 15 millimeter diameter foci. Search all of the brain regions in a pre-specified order from one side to the other to avoid any omission.For example, search from the frontal lobe insula and basil ganglion, temporal lobe, parietal lobe, and occipital lobe, cerebellum, and brainstem. To confirm the presence of the silent lacunes, view the FLAIR NT1 weighted images in which the lacunes can be observed as hypointense foci of two to 15 millimeter diameters, often with a hyperintense rim and the T2 weighted images in which then the lacunes are hyperintense. To identify cerebral microbleeds as punctate, or two to 10 millimeter diameter round oval hypointense foci their locations, load susceptibility weighted images into the software, and use the Brain Observer micro bleed scale to divide the entire brain region into seven anatomical locations.A participant is considered to have strictly low bar cerebral microbleeds when all of the lesions are confined to the cortex and the subcortical white matter. To identify white matter hyperintensities as bilateral, almost symmetrical hyperintense areas, view the T2 weighted and FLAIR images. Use the Fazekas scale to score periventricular hyperintensities appearing as caps or pencil thin lining as grade one foci, smooth halos as grade two, and irregular signals extending into the deep white matter as grade three.Rate deep white matter hyperintensities appearing as punctate foci as grade one, small confluent areas as grade two, and large confluent areas as grade three. In this representative analysis, the mean age of the 398 participants was 72 years, and 213 of the participants were men. Here the neuropsychological assessment results for the participants are shown.One or more types of silent cerebrovascular lesions were found in 169 participants, with 35 participants exhibiting two types, and 17 exhibiting three types. Only five participants had all four types of silent cerebrovascular lesions. The data confirmed an independent association between the burden of periventricular white matter hyperintensities, and a poorer performance in executive function and information processing speed.An increasing load of cerebral microbleeds was associated with impaired language related performance, and additional adjustment for vascular risk factors and other types of silent cerebrovascular lesions did not affect the independent impact of cerebral microbleeds on language function. Although there was a significant association between the presence of silent lacunes and a poorer performance on executive function, this association was lost following additional correction for other types of silent cerebrovascular lesions. While it is not difficult to learn this neuro-psychological test, it could be challenging to follow the same standardized procedure on hundreds of patients over several years.A unified standard should be adopted for both the neuropsychological assessments and rating of the MRI lesions for participants. These procedures should be reviewed periodically to ensure that uniformity. Some of the neuropsychological tests have overlaps in the evaluated domain.In the future, computer-based assessment can be more precise and additional function on your imaging study can be applied to specific cognitive domain.

evaluation-cognitive-performance-hypertensive-patients-with-silent

Research

JoVE Journal

Behavior

2.8K visualizações.  The First Affiliated Hospital of Wenzhou Medical University. Lesões cerebrovasculares silenciosas podem causar vários prejuízos funcionais e déficits cognitivos. No entanto, os efeitos distintos de diferentes tipos de lesões no desempenho cognitivo permanecem incertos. Utilizando testes neuropsicológicos e ressonância magnética multi-seqüência, podemos avaliar se vários tipos de lesões cerebrovasculares estão diferencialmente associados a déficits em domínios cognitivos específicos.Demonstrando os procedimentos de estudo será fe...