Influence of vascular risk factors and neuropsychological profile on functional performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study (MILES)
L. Ciolli
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorF. Pescini
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorE. Salvadori
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. Del Bene
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorG. Pracucci
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. Poggesi
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorS. Nannucci
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorR. Valenti
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. M. Basile
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorF. Squarzanti
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorS. Bianchi
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorM. T. Dotti
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorE. Adriano
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorM. Balestrino
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorA. Federico
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorC. Gandolfo
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorD. Inzitari
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorCorresponding Author
L. Pantoni
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Correspondence: L. Pantoni, NEUROFARBA Department, Neuroscience section, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy (tel.: +39 055 7945519; fax: +39 055 4298461; e-mail: [email protected]).Search for more papers by this authorL. Ciolli
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorF. Pescini
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorE. Salvadori
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. Del Bene
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorG. Pracucci
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. Poggesi
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorS. Nannucci
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorR. Valenti
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorA. M. Basile
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorF. Squarzanti
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorS. Bianchi
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorM. T. Dotti
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorE. Adriano
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorM. Balestrino
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorA. Federico
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
Search for more papers by this authorC. Gandolfo
Department of Neurological Sciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Search for more papers by this authorD. Inzitari
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Search for more papers by this authorCorresponding Author
L. Pantoni
NEUROFARBA Department, Neuroscience section, University of Florence, Florence, Italy
Correspondence: L. Pantoni, NEUROFARBA Department, Neuroscience section, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy (tel.: +39 055 7945519; fax: +39 055 4298461; e-mail: [email protected]).Search for more papers by this authorAbstract
Background and purpose
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown.
Methods
In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL).
Results
We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (β = −0.418, P < 0.003) in CADASIL patients and the executive function index (β = −0.321, P = 0.028) in ARL.
Conclusions
This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.
References
- 1Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol 2009; 8: 643–653.
- 2Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain 2004; 127: 2031–2038.
- 3Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke 2010; 41: 630–634.
- 4Amberla K, Wäljas M, Tuominen S, et al. Insidious cognitive decline in CADASIL. Stroke 2004; 35: 1598–1602.
- 5Charlton RA, Morris RG, Nitkunan A, Markus HS. The cognitive profiles of CADASIL and sporadic small vessel disease. Neurology 2006; 66: 1523–1526.
- 6Buffon F, Porcher R, Hernandez K, et al. Cognitive profile in CADASIL. J Neurol Neurosurg Psychiatry 2006; 77: 175–180.
- 7O'Sullivan M, Morris RG, Huckstep B, Jones DK, Williams SC, Markus HS. Diffusion tensor MRI correlates with executive dysfunction in patients with ischemic leukoaraiosis. J Neurol Neurosurg Psychiatry 2004; 75: 441–447.
- 8Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005; 128: 2034–2041.
- 9Lamar M, Dannhauser TM, Walker Z, Rodda JE, Cutinha DJ, Shergill SS. Memory complaints with and without memory impairment: the impact of leukoaraiosis on cognition. J Int Neuropsychol Soc 2011; 17: 1104–1112.
- 10Epelbaum S, Benisty S, Reyes S, et al. Verbal memory impairment in subcortical ischemic vascular disease: a descriptive analysis in CADASIL. Neurobiol Aging 2011; 32: 2172–2182.
- 11Pescini F, Cesari F, Giusti B, et al. Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2010; 41: 218–223.
- 12Folstein 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.
- 13Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. Am J Neuroradiol 1987; 8: 421–426.
- 14Gélinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. Am J Occup Ther 1999; 53: 471–481.
- 15Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9: 179–186.
- 16Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression rating scale: a preliminary report. J Psychiatr Res 1982-1983; 17: 37–49.
- 17Baezner H, Blahak C, Poggesi A, et al. LADIS Study Group. Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 2008; 70: 935–942.
- 18Madureira S, Verdelho A, Moleiro C, et al. Neuropsychological predictors of dementia in a three-year follow-up period: data from the LADIS study. Dement Geriatr Cogn Disord 2010; 29: 325–334.
- 19Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572. Erratum in: JAMA 2003;290:197.
- 20 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26: 5–20.
- 21 National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143–3421.
- 22Hatano S. Experience from a multicentre stroke registry: a preliminary report. Bulletin WHO 1976; 54: 541–553.
- 23 Headache Classification Committee. The International Classification of Headache Disorders, 2nd Edition. Cephalalgia 2004; 24: 1–160.
- 24 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association, 1994.
- 25Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005; 24: 51–62.
- 26Inzitari D, Pracucci G, Poggesi A, et al. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ 2009; 339: b2477.
- 27Dichgans M, Filippi M, Brüning R, et al. Quantitative MRI in CADASIL: correlation with disability and cognitive performance. Neurology 1999; 52: 1361–1367.
- 28Bruening R, Dichgans M, Berchtenbreiter C, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance. Am J Neuroradiol 2001; 22: 1268–1274.
- 29Viswanathan A, Gschwendtner A, Guichard JP, et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007; 69: 172–179.
- 30Holtmannspötter M, Peters N, Opherk C, et al. Diffusion magnetic resonance histograms as a surrogate marker and predictor of disease progression in CADASIL: a two-year follow-up study. Stroke 2005; 36: 2559–2565.
- 31Brookes RL, Willis TA, Patel B, Morris RG, Markus HS. Depressive symptoms as a predictor of quality of life in cerebral small vessel disease, acting independently of disability; a study in both sporadic small vessel disease and CADASIL. Int J Stroke 2012. 8: 510–517.
- 32Liao D, Cooper L, Cai J, et al. Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study. Stroke 1996; 27: 2262–2270.
- 33Longstreth WT Jr, Manolio TA, Arnold A, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 1996; 27: 1274–1282.
- 34Breteler MM, van Swieten JC, Bots ML, et al. Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 1994; 44: 1246–1252.
- 35Dufouil C, de Kersaint-Gilly A, Besançon V, et al. Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort. Neurology 2001; 56: 921–926.
- 36O'Sullivan M, Ngo E, Viswanathan A, et al. Hippocampal volume is an independent predictor of cognitive performance in CADASIL. Neurobiol Aging 2009; 30: 890–897.
- 37Jouvent E, Mangin JF, Duchesnay E, et al. Longitudinal changes of cortical morphology in CADASIL. Neurobiol Aging 2012; 33: 1002.
- 38Gray F, Polivka M, Viswanathan A, Baudrimont M, Bousser MG, Chabriat H. Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol 2007; 66: 597–607.
- 39Viswanathan A, Gray F, Bousser MG, Baudrimont M, Chabriat H. Cortical neuronal apoptosis in CADASIL. Stroke 2006; 37: 2690–2695.
- 40Duering M, Righart R, Csanadi E, et al. Incident subcortical infarcts induce focal thinning in connected cortical regions. Neurology 2012; 79: 2025–2028.
- 41O'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.
