J Clin Neurol.  2011 Dec;7(4):210-214. 10.3988/jcn.2011.7.4.210.

Effects of Lacunar Infarctions on Cognitive Impairment in Patients with Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

• Lee JS
• Choi JC
• Kang SY
• Kang JH
• Na HR
• Park JK

• KMID: 2179006
• DOI: http://doi.org/10.3988/jcn.2011.7.4.210

Abstract

BACKGROUND AND PURPOSE
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL.
METHODS
We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)].
RESULTS
A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis.
CONCLUSIONS
These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.

Keyword

cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy; lacunes; cerebral microbleeds; white-matter hyperintensities

MeSH Terms

Alzheimer Disease
CADASIL
Cognition
Humans
Leukoencephalopathies
Prospective Studies
Psychometrics
Stroke, Lacunar

Figure

• 

  Fig. 1 An example of the volumetric analysis. Whole brain volume was calculated after removing nonbrain tissue (B) and the ventricles (C). The volume of the white-matter hyperintensity was calculated semiautomatically using threshold filtering (D).

Reference

1. Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 1996. 383:707–710.

2. Chabriat H, Vahedi K, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995. 346:934–939.

3. Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psychiatry. 2005. 162:2078–2085.

4. Benisty S, Hernandez K, Viswanathan A, Reyes S, Kurtz A, O'Sullivan M, et al. Diagnostic criteria of vascular dementia in CADASIL. Stroke. 2008. 39:838–844.

5. O'Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001. 56:628–634.

6. Viswanathan A, Gschwendtner A, Guichard JP, Buffon F, Cumurciuc R, O'Sullivan M, et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology. 2007. 69:172–179.

7. Liem MK, van der Grond J, Haan J, van den Boom R, Ferrari MD, Knaap YM, et al. Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL. Stroke. 2007. 38:923–928.

8. Liem MK, Lesnik Oberstein SA, Haan J, van der Neut IL, Ferrari MD, van Buchem MA, et al. MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study. Neurology. 2009. 72:143–148.

9. Viswanathan A, Godin O, Jouvent E, O'Sullivan M, Gschwendtner A, Peters N, et al. Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL. Neurobiol Aging. 2010. 31:1629–1636.

10. Viswanathan A, Guichard JP, Gschwendtner A, Buffon F, Cumurcuic R, Boutron C, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain. 2006. 129:2375–2383.

11. Jouvent E, Viswanathan A, Mangin JF, O'Sullivan M, Guichard JP, Gschwendtner A, et al. Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL. Stroke. 2007. 38:1786–1790.

12. Kang Y, Na DL, Hahn S. A validity study on the Korean mini-mental state examination (K-MMSE) in dementia patients. J Korean Neurol Assoc. 1997. 15:300–308.

13. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984. 141:1356–1364.

14. Suh GH, Mohs RC. Development of the Korean version of Alzheimers Disease Assessment Scale (ADAS-K) to assess cognition in dementia. J Korean Geriatr Soc. 2003. 7:269–277.

15. Reitan RM. Trail Making Test. Manual for Administration and Scoring. 1959. Bloomington, IN: Indiana University.

16. Yi H, Chin J, Lee BH, Kang Y, Na DL. Development and validation of Korean version of Trail Making Test for elderly persons. Dement Neurocognitive Disord. 2007. 6:54–66.

17. Madureira S, Verdelho A, Ferro J, Basile AM, Chabriat H, Erkinjuntti T, et al. Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data. Neuroepidemiology. 2006. 27:101–116.

18. Golden C, Freshwater SM. Stroop Color and Word Test. 2002. Wood Dale, IL: Stoelting.

19. Bokura H, Kobayashi S, Yamaguchi S. Distinguishing silent lacunar infarction from enlarged Virchow-Robin spaces: a magnetic resonance imaging and pathological study. J Neurol. 1998. 245:116–122.

20. Koennecke HC. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology. 2006. 66:165–171.

21. Kang SY, Oh JH, Kang JH, Choi JC, Lee JS. Nerve conduction studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neurol. 2009. 256:1724–1727.

22. Lee JS, Choi JC, Kang SY, Kang JH, Lee SH, Kim JH, et al. Olfactory identification deficits in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Eur Neurol. 2010. 64:280–285.