Background: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. Methods: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65–84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). Results: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. Conclusion: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.

Keywords:
Subcortical ischemic vascular disease, Small vessel disease, White matter changes, Vascular cognitive impairment
1.
Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC: Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426–436.
2.
Erkinjuntti T: Vascular cognitive deterioration and stroke. Cerebrovasc Dis 2007;24(suppl 1):189–194.
3.
Bowler JV: Modern concept of vascular cognitive impairment. Br Med Bull 2007;83:291–305.
4.
O’Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST: Vascular cognitive impairment. Lancet Neurol 2003;2:89–98.
5.
Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW: Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm 2000;59(suppl):23–30.
6.
Erkinjuntti T: Subcortical vascular dementia. Cerebrovasc Dis 2002;13(suppl 2):58–60.
7.
Chui H: Subcortical ischemic vascular dementia (SIVD). Neurol Clin 2007;25:717–740.
8.
Shim YS, Yang D-W, Kim B-S, Shon YM, Chung Y-A: Comparison of regional blood flow in two sets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT. J Neurol Sci 2006;250:85–91.
9.
Pohjasvaara T, Mäntylä R, Ylikoski R, Kaste M, Erkinjuntti T: Clinical features of MRI-defined subcortical vascular disease. Alzheimer Dis Assoc Disord 2003;17:236–242.
10.
Jokinen H, Kalska H, Mäntylä R, Pohjasvaara T, Ylikoski R, Hietanen M, Salonen O, Kaste M, Erkinjuntti T: Cognitive profile of subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2006;77:28–33.
11.
Pantoni L, Basile AM, Pracucci G, Asplund K, Bogousslavsky J, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, O’Brien J, Scheltens P, Visser MC, Wahlund L-O, Waldemar G, Wallin A, Inzitari D: 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.
12.
Lawton MP, Brody EM: Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–186.
13.
Guidelines Subcommittee: 1999 World Health Organization-International Society of Hypertension guidelines for the management of hypertension. J Hypertens 1999;17:151–183.
14.
The 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 1997;20:1183–1197.
15.
National Cholesterol Education Program: Second report of the Expert Panel on detection, evaluation, and treatment of high cholesterol in adults (Adult Treatment Panel II). Circulation 1994;89:1333–1445.
16.
Alpert JS, Thygesen K, Antman E, Bassand JP: Myocardial infarction redefined – A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959–969.
17.
Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, Steward DE, Theroux P, Alpert JS, Eagle KA, Faxon DP, Fuster V, Gardner TJ, Gregoratos G, Russell RO, Smith SCJ: ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol 2000;36:970–1062.
18.
Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM, Grunwald MA, Levy D, Lytle BW, O’Rourke RA, Schafer WP, Williams SV, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson AJ, Russell RO, Ryan TJ, Smith SCJ: ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). J Am Coll Cardiol 1999;33:2092–2197.
19.
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB: A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85–M94.
20.
Yesavage JA: Geriatric Depression Scale. Psychopharmacol Bull 1988;24:709–711.
21.
Gelinàs 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.
22.
Madureira S, Verdelho A, Ferro J, Basile A-M, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O’Brien J, Pantoni L, Salvadori E, Scheltens P, Visser MC, Wahlund L-O, Waldemar G, Wallin A, Inzitari D: Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data. Neuroepidemiology 2006;27:101–116.
23.
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.
24.
Ferris SH: General measures of cognition. Int Psychogeriatr 2003;15(suppl 1):215–217.
25.
MacLeod CM: Half a century of research on the Stroop effect: an integrative review. Psychol Bull 1991;109:163–203.
26.
Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271–276.
27.
van Straaten ECW, Fazekas F, Rostrup E, Scheltens P, Schmidt R, Pantoni L, Inzitari D, Waldemar G, Erkinjuntti T, Mäntylä R, Wahlund L-O, Barkhof F: Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study. Stroke 2006;37:836–840.
28.
Scheltens P, Launer LJ, Barkhof F, Weinstein HC, van Gool WA: Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: interobserver reliability. J Neurol 1995;242:557–560.
29.
Longstreth WTJ, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, Enright PL, O’Leary D, Fried L: Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3,301 elderly people: the Cardiovascular Health Study. Stroke 1996;27:1274–1282.
30.
Bernal-Pacheco O, Román GC: Environmental vascular risk factors: new perspectives for stroke prevention. J Neurol Sci 2007;262:60–70.
31.
Wolf J, Lewicka J, Narkiewicz K: Obstructive sleep apnea: an update on mechanisms and cardiovascular consequences. Nutr Metab Cardiovasc Dis 2007;17:233–240.
32.
Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbergsweig D, Charlson M: ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997;54:915–922.
33.
Vataja R, Pohjasvaara T, Leppävuori A, Mäntylä R, Aronen HJ, Salonen O, Kaste M, Erkinjuntti T: Magnetic resonance imaging correlates of depression after ischemic stroke. Arch Gen Psychiatry 2001;58:925–931.
34.
Krishnan MS, O’Brien JT, Firbank MJ, Pantoni L, Carlucci G, Erkinjuntti T, Wallin A, Wahlund LO, Scheltens P, van Straaten EC, Inzitari D: Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study. Int J Geriatr Psychiatry 2006;21:983–989.
35.
O’Brien JT, Firbank MJ, Krishnan MS, van Straaten EC, van der Flier WM, Petrovic K, Pantoni L, Simoni M, Erkinjuntti T, Wallin A, Wahlund LO, Inzitari D: White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study. Am J Geriatr Psychiatry 2006;14:834–841.
36.
Libon DJ, Bogdanoff B, Leopold N, Hurka R, Bonavita J, Skalina S, Swenson R, Gitlin HL, Ball SK: Neuropsychological profiles associated with subcortical white matter alterations and Parkinson’s disease: implications for the diagnosis of dementia. Arch Clin Neuropsychol 2001;16:19–32.
37.
Kramer JH, Reed BR, Mungas D, Weiner MW, Chui H: Executive dysfunction in subcortical ischemic vascular disease. J Neurol Neurosurg Psychiatry 2002;72:217–220.
38.
Price CC, Jefferson AL, Merino JG, Heilman KM, Libon DJ: Subcortical vascular dementia. Integrating neuropsychological and neuroradiologic data. Neurology 2005;65:376–382.
39.
Tierney MC, Black SE, Szalai JP, Snow WG, Fisher RH, Nadon G, Chui HC: Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia. Arch Neurol 2001;58:1654–1659.
40.
Kramer JH, Mungas D, Reed BR, Schuff N, Weiner MW, Miller BL, Chui HC: Forgetting in dementia with and without subcortical lacunes. Clin Neuropsychol 2004;18:32–40.
41.
Schmidtke K, Hüll M: Neuropsychological differentiation of small vessel disease, Alzheimer’s disease and mixed dementia. J Neurol Sci 2002;203–204:17–22.
42.
Tekin S, Cummings JL: Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647–654.
43.
Pugh KG, Lipsitz LA: The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging 2002;23:421–431.
44.
Kril JJ, Patel S, Harding AJ, Halliday GM: Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss. J Neurol Neurosurg Psychiatry 2002;72:747–751.
45.
Seshadri S, Wolf PA, Beiser A, Elias MF, Au R, Kase CS, D’Agostino RB, DeCarli C: Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study. Neurology 2004;63:1591–1599.
46.
van der Flier WM, van Straaten ECW, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P: Small vessel disease and general cognitive function in non-disabled elderly: the LADIS study. Stroke 2005;36:2116–2120.
47.
Baezner H, Blahak C, Poggesi A, Pantoni L, Inzitari D, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Langhorne P, O’Brien J, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Hennerici MG: Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 2008;70:935–942.
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