Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.

1.
Smith EE, Egorova S, Blacker D, Killiany RJ, Muzikansky A, Dickerson BC, Tanzi RE, Albert MS, Greenberg SM, Guttmann CR: Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol 2008;65:94-100.
2.
Silbert LC, Howieson DB, Dodge H, Kaye JA: Cognitive impairment risk: white matter hyperintensity progression matters. Neurology 2009;73:120-125.
3.
Gouw AA, van der Flier WM, Fazekas F, van Straaten EC, Pantoni L, Poggesi A, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G, et al: Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke 2008;39:1414-1420.
4.
Verdelho A, Madureira S, Ferro JM, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O'Brien J, Pantoni L, et al: Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study. J Neurol Neurosurg Psychiatry 2007;78:1325-1330.
5.
Madureira S, Verdelho A, Moleiro C, Ferro JM, Erkinjuntti T, Jokinen H, Pantoni L, Fazekas F, Van der Flier W, Visser M, 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.
6.
Swan GE, DeCarli C, Miller B, Reed T, Wolf P, Jack L, Carmelli D: Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology 1998;51:986-993.
7.
Gudmundsson P, Olesen P, Simoni M, Pantoni L, Östling S, Kern S, Guo X, Skoog I: White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70-year-olds followed over 10 years. Eur J Neurol 2015;22:781-788, e49-e50.
8.
Kloppenborg RP, Nederkoorn PJ, Geerlings MI, van den Berg E: Presence and progression of white matter hyperintensities and cognition: a meta-analysis. Neurology 2014;82:2127-2138.
9.
Pantoni L, Basile AM, Pracucci G, Asplund K, Bogousslavsky J, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, 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.
10.
Madureira S, Verdelho A, Ferro J, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O'Brien J, Pantoni L, 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.
11.
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.
12.
Lawton MP, Brody EM: Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179-186.
13.
Folstein M, Folstein S, McHugh PJ: Mini-Mental State: a practical method for grading the cognitive state of patients for clinicians. J Psychiatr Res 1975;12:189-198.
14.
Mohs RC, Rosen WG, Davis KL: The Alzheimer's Disease Assessment Scale: an instrument for assessing treatment efficacy. Psychopharmacol Bull 1983;19:448-450.
15.
Rosen W, Mohs R, Davis K: A new rating scale for Alzheimer's disease. Am J Psychiatry 1984;141:1356-1364.
16.
Ferris S: Cognitive outcome measures. Alzheimer Dis Assoc Disord 1999;13(suppl 3):S140-S142.
17.
Reitan R: Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-276.
18.
Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643-662.
19.
Libon D, Mattson R, Glosser G, Kaplan E, Malamut B, Sands LP, Swenson R, Cloud B: A nine-word version of the California Verbal Learning Test. Clin Neuropsychol 1996;10:237-244.
20.
Prins ND, van Straaten EC, van Dijk EJ, Simoni M, van Schijndel RA, Vrooman HA, Koudstaal PJ, Scheltens P, Breteler MM, Barkhof F: Measuring progression of cerebral white matter lesions on MRI: visual rating and volumetrics. Neurology 2004;62:1533-1539.
21.
Ylikoski R, Jokinen H, Andersen P, Salonen O, Madureira S, Ferro J, Barkhof F, van der Flier W, Schmidt R, Fazekas F, et al: Comparison of the Alzheimer's Disease Assessment Scale Cognitive Subscale and the Vascular Dementia Assessment Scale in differentiating elderly individuals with different degrees of white matter changes. The LADIS Study. Dement Geriatr Cogn Disord 2007;24:73-81.
22.
Verdelho A, Madureira S, Moleiro C, Ferro JM, Santos CO, Erkinjuntti T, Pantoni L, Fazekas F, Visser M, Waldemar G, et al: White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study. Neurology 2010;75:160-167.
23.
Petersen R, Doody R, Kurtz A, Mohs R, Morris J, Rabins P, Ritchie K, Rossor M, Thal L, Winblad B: Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-1992.
24.
Wentzel C, Rockwood K, MacKnight C, Hachinski V, Hogan D, Feldman H, Østbye T, Wolfson C, Gauthier S, Verreault R: Progression of impairment in patients with vascular cognitive impairment without dementia. Neurology 2001;57:714-716.
25.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
26.
Román G, Tatemichi T, Erkinjuntti T, Cummings J, Masdeu J, Garcia J, Amaducci L, Orgogozo J, Brun A, Hofman A, et al: Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250-260.
27.
McKhann G, Albert M, Grossman M, Miller B, Dickson D, Trojanowski J: Clinical and pathological diagnosis of frontotemporal dementia. Arch Neurol 2001;58:1803-1809.
28.
McKeith I, Galasko D, Kosaka K, Perry E, Dickson D, Hansen L, Salmon D, Lowe J, Mirra S, Byrne E, et al: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47:1113-1124.
29.
Uttl B, Graf P: Color-Word Stroop test performance across the adult life span. J Clin Exp Neuropsychol 1997;19:405-420.
30.
O'Bryant SE, Humphreys JD, Smith GE, Ivnik RJ, Graff-Radford NR, Petersen RC, Lucas JA: Detecting dementia with the Mini-Mental State Examination in highly educated individuals. Arch Neurol 2008;65:963-967.
31.
Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F: Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. Lancet 2003;361:2046-2048.
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