Background and Purpose: Recurrent strokes and cognitive dysfunction are the major symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, emotional disturbances in CADASIL patients are incompletely understood. The aim of this study was to investigate emotional disturbances in CADASIL and their impact on the patients' quality of life (QOL) and caregiver burden. Methods: From 54 patients who were diagnosed as CADASIL between January 2000 and August 2012 in the Asan Medical Center, Seoul, Korea, 23 patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale was used for the assessment of depressive emotional disturbances (DED). For nondepressive emotional disturbances (NDED), the criteria of Kim and Choi-Kwon [Neurology 2000;54:1805-1810] were used for emotional incontinence (excessive/inappropriate expression of laughing or crying), and the modified Spielberger Trait Anger Scale was used for anger proneness (excessive/inappropriate expression of anger). Patients' QOL and caregiver burden were assessed with stroke-specific emotional QOL and the Sense of Competence Questionnaire (SCQ), respectively. Functional disability was assessed by the modified Rankin scale (mRS), and white matter ischemic changes and microbleeds were analyzed using brain magnetic resonance images. Results: Twelve patients (52.2%) had various emotional disturbances including DED (n = 10, 43.5%) and NDED (n = 7, 30.4%). The presence of any emotional disturbances was associated with thalamic (p = 0.012) and cortical (p = 0.037) microbleeds, mRS (p = 0.001), cognitive impairment (p = 0.002), patients' low QOL (p = 0.009) and increased caregiver burden (p = 0.002). DED was associated with multiple (≥10) microbleeds (p = 0.039), cognitive impairment (p = 0.030) and mRS (p = 0.030), and negatively influenced all domains of patients' QOL and caregiver burden. NDED was associated with cortical microbleeds (p = 0.017) and mRS (p = 0.014). Unlike DED, NDED was not associated with patients' poor QOL, except for thinking domain, but was significantly related to total SCQ and subscales 1 and 2 of SCQ (p = 0.012). Conclusions: More than half the CADASIL patients had emotional disturbances, either DED or NDED. Both are associated with patients' poor QOL and increased caregiver burden, the former more markedly than the latter. Considering that CADASIL is a progressive disease with deteriorating patients' QOL, physicians have to pay more attention to emotional problems in CADASIL patients. Treatment strategies should be investigated in this regard to improve patients' QOL and reduce caregiver burden.

Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E: Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383:707-710.
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.
Choi JC: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a genetic cause of cerebral small vessel disease. J Clin Neurol 2010;6:1-9.
Lesnik Oberstein SA, van den Boom R, van Buchem MA, van Houwelingen HC, Bakker E, Vollebregt E, Ferrari MD, Breuning MH, Haan J, Dutch CRG: Cerebral microbleeds in CADASIL. Neurology 2001;57:1066-1070.
Dichgans M, Holtmannspotter M, Herzog J, Peters N, Bergmann M, Yousry TA: Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke 2002;33:67-71.
Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F: MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999;52:991-994.
Valenti R, Pescini F, Antonini S, Castellini G, Poggesi A, Bianchi S, Inzitari D, Pallanti S, Pantoni L: Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview. Acta Neurol Scand 2011;124:390-395.
Valenti R, Poggesi A, Pescini F, Inzitari D, Pantoni L: Psychiatric disturbances in CADASIL: a brief review. Acta Neurol Scand 2008;118:291-295.
Choi-Kwon S, Han K, Choi S, Suh M, Kim YJ, Song H, Cho KH, Nah HW, Kwon SU, Kang DW, Kim JS: Poststroke depression and emotional incontinence: factors related to acute and subacute stages. Neurology 2012;78:1130-1137.
Choi-Kwon S, Han SW, Kwon SU, Kang DW, Choi JM, Kim JS: Fluoxetine treatment in poststroke depression, emotional incontinence, and anger proneness: a double-blind, placebo-controlled study. Stroke 2006;37:156-161.
Calvert T, Knapp P, House A: Psychological associations with emotionalism after stroke. J Neurol Neurosurg Psychiatry 1998;65:928-929.
Choi-Kwon S, Kim HS, Kwon SU, Kim JS: Factors affecting the burden on caregivers of stroke survivors in South Korea. Arch Phys Med Rehabil 2005;86:1043-1048.
Williams JB, Kobak KA: Development and reliability of a structured interview guide for the Montgomery-Asberg Depression Rating Scale (SIGMA). Br J Psychiatry 2008;192:52-58.
Montgomery SA, Asberg M: A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389.
Ahn YM LK, Yi JS, Kang MH, Kim DH, Kim JL, et al: A validation study of the Korean version of the Montgomery-Asberg Depression Rating Scale. J Korean Neuropsychiatr Assoc 2005;44:466-476.
Macfadden W, Adler CM, Turkoz I, Haskins JT, Turner N, Alphs L: Adjunctive long-acting risperidone in patients with bipolar disorder who relapse frequently and have active mood symptoms. BMC Psychiatry 2011;11:171.
Kim JS, Choi-Kwon S: Poststroke depression and emotional incontinence: correlation with lesion location. Neurology 2000;54:1805-1810.
Jeon KG KD, Lee JS: Development of the STAXI-K: iv. Korean J Art Ther 2000;7:33-48.
Spielberger C, Jacobs G, Russell S, Crane R: Assessment of Anger: The State-Trait Anger-Scale. Hillsdale, Erlbaum, 1983.
Kim JS, Choi S, Kwon SU, Seo YS: Inability to control anger or aggression after stroke. Neurology 2002;58:1106-1108.
Kang Y ND, 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.
Reisberg B, Ferris SH, de Leon MJ, Crook T: The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-1139.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state': a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
Williams LS, Weinberger M, Harris LE, Clark DO, Biller J: Development of a stroke-specific quality of life scale. Stroke 1999;30:1362-1369.
Scholte op Reimer WJ, de Haan RJ, Pijnenborg JM, Limburg M, van den Bos GA: Assessment of burden in partners of stroke patients with the Sense of Competence Questionnaire. Stroke 1998;29:373-379.
Nah HW, Kang DW, Kwon SU, Kim JS: Diversity of single small subcortical infarctions according to infarct location and parent artery disease: analysis of indicators for small vessel disease and atherosclerosis. Stroke 2010;41:2822-2827.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351-356.
Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study G: Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009;8:165-174.
Zhang M, Chen M, Wang Q, Yun W, Zhang Z, Yin Q, Huang Q, Zhu W: Relationship between cerebral microbleeds and cognitive function in lacunar infarct. J Int Med Res 2013;41:347-355.
Choi EJ, Choi CG, Kim JS: Large cerebral artery involvement in CADASIL. Neurology 2005;65:1322-1324.
Kim Y, Choi EJ, Choi CG, Kim G, Choi JH, Yoo HW, Kim JS: Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation. Neurology 2006;66:1511-1516.
Choi JC, Song SK, Lee JS, Kang SY, Kang JH: Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C. J Stroke Cerebrovasc Dis 2013;22:126-131.
Yin XZ, Ding MP, Zhang BR, Liu JR, Zhang L, Wang PZ, Zhou FY, Zhao GH: Report of two Chinese families and a review of Mainland Chinese CADASIL patients. J Neurol Sci 2009;279:88-92.
Newman SC: The prevalence of depression in Alzheimer's disease and vascular dementia in a population sample. J Affect Disord 1999;52:169-176.
Winter Y, Korchounov A, Zhukova TV, Bertschi NE: Depression in elderly patients with Alzheimer dementia or vascular dementia and its influence on their quality of life. J Neurosci Rural Pract 2011;2:27-32.
Cummings JL: Frontal-subcortical circuits and human behavior. Arch Neurol 1993;50:873-880.
Tang WK, Chen YK, Lu JY, Chu WC, Mok VC, Ungvari GS, Wong KS: Cerebral microbleeds and depression in lacunar stroke. Stroke 2011;42:2443-2446.
Tang WK, Chen YK, Lu JY, Mok VC, Xiang YT, Ungvari GS, Ahuja AT, Wong KS: Microbleeds and post-stroke emotional lability. J Neurol Neurosurg Psychiatry 2009;80:1082-1086.
Lavretsky H, Zheng L, Weiner MW, Mungas D, Reed B, Kramer JH, Jagust W, Chui H, Mack WJ: The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. Int J Geriatr Psychiatry 2008;23:1040-1050.
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