| Abstract|| |
The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer's disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main changes in the brain in VCI include cerebral infarcts, vascular cognitive impairment is thought to be due to factors beyond acute infarcts. Cerebral white matter lesions and silent brain infarcts are considered to be risk factors for VCI. The prevalence of VCI is high and this entity is poised to become the silent epidemic of the 21st century. Cognitive impairment due to cerebrovascular disease can to some extent be improved, and VCI prevented, if vascular risk factors are brought under control and strokes do not recur. Therefore, strategies that focus on the prevention and treatment of the cognitive impairment associated with cerebrovascular disease are high priority healthcare objectives.
Keywords: Dementia, vascular cognitive impairment, stroke, vascular dementia, vascular risk factors
|How to cite this article:|
Suvarna A. Vascular cognitive impairment. Indian J Psychiatry 2009;51, Suppl S1:61-4
| Introduction|| |
Cognitive impairment that is caused by or associated with vascular factors has been termed "vascular cognitive impairment" (VCI).  VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. There is increasing evidence that patients with clinically significant cognitive impairment in association with vascular disease frequently do not fulfill the traditional criteria of dementia.  As the condition is preventable to a large extent, it is important to identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia. 
| Magnitude of VCI|| |
Studies have shown that up to 64% of persons who have experienced a stroke have some degree of cognitive impairment  with up to a third developing frank dementia.  Conversely, postmortem pathological studies indicate that up to 34% of dementia cases show significant vascular pathology.  VCI is therefore poised to become the silent epidemic of the 21st century.  Vascular dementia (VaD) is the second most common cause of dementia after Alzheimer disease (AD), and in some Asian countries, it is the most frequent cause. , The prevalence of VaD ranges from 1 to 8.8%. , An epidemiological study from India found VaD to account for 39% of dementias compared with 54% of AD.  Post-stroke dementia, affects about 30% of patients older than 65 years after ischemic stroke.  In a hospital based stroke clinic in South India, 75 consecutive stroke patients were evaluated for cognitive impairment three months after stroke. Post stroke dementia was detected in 20 (26.6%), milder form of cognitive impairment in 20 (26.6%) and no cognitive impairment in 25 patients (33%) using a standard neuropsychological battery of tests. 
Cardiovascular (CV) risk factors that include diabetes, hypertension, hyperlipidemia, and smoking are highly prevalent and cardiovascular diseases contribute significantly to mortality and disability.  There is increasing evidence from India and other countries that CV risk factors are associated with an increased risk of cognitive decline and dementia. , Cognitive impairment due to cerebrovascular disease can to some extent be improved, and VCI prevented, if vascular risk factors are brought under control and strokes do not recur.  Therefore strategies that focus on the prevention and treatment of the cognitive impairment associated with cerebrovascular disease are high priority healthcare objectives.
| Pathophysiology|| |
Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main changes in the brain in VCI include cerebral infarcts, VCI is thought to be due to factors beyond acute infarcts.  Cerebral white matter lesions (WML) and silent brain infarcts are considered to be risk factors for dementia. , Large artery disease, small artery disease, cardioembolism are important underlying causes of VCI. Vascular mechanisms underlying VCI are influenced by the pattern of stroke mechanisms, which differ among Asian countries compared with the west; small artery and intracranial large artery disease contribute to a larger proportion of underlying vascular mechanisms in India. , Increasing evidence suggests that hippocampal and cerebral atrophy is associated with VCI.
| Clinical Spectrum of VCI|| |
VCI forms a spectrum that includes VaD, mixed AD with a vascular component, and VCI that does not meet dementia criteria. In a hospital based registry in South India, of 87 patients with VCI, 59.8% had VaD, 31% had cognitive impairment without dementia and 9.2% had mixed dementia.  VaD is a group of syndromes that represent a clinicoradiologic and pathological spectrum. Three subtypes recognizable in clinical practice include, multi infarct dementia characterized by recurrent stroke, stepwise course, focal neurological symptoms and signs and multiple cerebral infarcts on brain imaging, strategic infarct dementia characterized by an abrupt onset of memory impairment or behavioral change in association with a single, strategically placed infarct, and subcortical vascular dementia due to small-vessel disease, which leads to white matter and deep subcortical gray and white matter demyelination and lacunar infarcts.  A hospital based study in India, characterizing pattern of VaD diagnosed according to Neurological Disorders and Stroke (NINDS) AIREN criteria demonstrated that subcortical dementia was the most common form of VaD, followed by cortical-subcortical dementia. 
In comparison to AD, there is a general consensus that episodic memory is more impaired in AD, and that executive/attentional processing is more impaired in vascular dementia, especially in patients with subcortical VaD.  Some recent data suggest a less exclusive role for executive dysfunction in VCI than was previously proposed.  Patients with VaD also showed greater impairment in both semantic memory and visuospatial/perceptual function than the patients with Alzheimer's disease.  Further, depressive symptoms were more common in patients with VCI. 
Recent evidence indicates a complex interaction between VaD and AD. Longitudinal studies have shown that vascular risk factors pre-dispose to both cerebrovascular disease and AD.  Further, considerable overlap between vascular and AD pathology exists in dementia patients.  Diffuse neurochemical abnormalities, especially cholinergic deficits have been identified in VaD. Furthermore, brain vascular and neurodegenerative pathologies may be additive in the way in which they influence clinical presentation.  A population based autopsy study found pure VaD in 13% of dementias and mixed VaD and AD in 12% in comparison to 51% of AD.  The results suggest that clinical diagnosis of dementia made during life may fail to reflect the pathogenic complexity of this condition in elderly persons.
| VCI Harmonization Standards|| |
A uniform cognitive, clinical, imaging and pathological profile typical of VCI has not been identified. The reasons are partly methodological and also due to heterogeneity of patient groups in studies. In an attempt to identify and describe individuals with VCI, particularly in the early stages, The National Institute for NINDS and the Canadian Stroke Network (CSN) developed common standards in clinical diagnosis, epidemiology, brain imaging, neuropathology, experimental models, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of VCI.  Using the same standards was thought to help identify individuals in the early stages of cognitive impairment, make studies comparable, and integrate knowledge, thereby accelerating the pace of progress of understanding, preventing and treating VCI.
| Course and Outcome of Disease|| |
Nearly half of elderly with mild cognitive impairment (MCI) due to vascular disease converted to dementia after five years in the Canadian Study of Health and Aging. 
Further, a follow up study of people with VCI, AD, and 'No cognitive impairment,' showed that most people with VCI showed readily detectable progression by 30 months and depressive symptoms and impaired judgment progressed more commonly in patients with VCI.  In a longitudinal study of VaD due to subcortical lacunar infarcts, progressive cognitive decline was determined mainly by the occurrence of new vascular episodes and severity of the cognitive impairment at baseline, providing evidence that ongoing vascular insult is responsible for progression of disease.  Vascular dementia shortens life expectancy. A 5-year follow-up study of incident dementia cases  found the mortality risk was 3.3 times higher for vascular dementia compared with non-demented people.
| Treatment and Prevention|| |
Attempts to reverse or delay progression of cognitive impairment due to cerebrovascular disease have given grounds for hope of treatment of VAD. Based on the various pathophysiological mechanisms proposed to underlie VaD, a wide range of drugs have been tried to treat VaD.
In a randomized, trial of 325 mg/day aspirin (vs. no aspirin) conducted on multi-infarct dementia patients. The group of aspirin patients showed significantly higher cognitive scores than the untreated group.  The use of acetylcholinesterase inhibitors is based on the demonstration of existence of cholinergic deficits in pure VaD. Donepezil tested in two double-blind, placebo-controlled trials on patients diagnosed with possible or probable VaD showed significant improvement in cognition (ADAS-cog, MMSE) and global functioning scores.  Galantamine, rivastigmine, and memantine have also demonstrated improvement in cognition and caregiver stress. Pentoxifylline, propentofylline, citicholine, hydergine, nicergoline, and piracetam, were found to have a positive effect on cognitive function and behavior.
The prevention of stroke recurrence through the control of risk factors, by carotid endarterectomy as well as the use of antithrombotic drugs (warfarin or antiplatelet agents), is likely to reduce the incidence of VaD and mixed dementia. Decreased incidence of dementia associated with antihypertensive treatment using candesartan, nitrendipine and perindopril has been demonstrated. , Some studies suggest that the use of lipid-lowering agents lowers the risk of dementia and protects against cognitive decline. 
| Conclusions|| |
Vascular risk factors and cerebrovascular disease are now recognized to account for a major proportion of cognitive disorders, including degenerative dementias. Emphasis has shifted from diagnosis of VaD based on restrictive criteria to include a broader spectrum of disease VCI that includes mixed dementia and cognitive impairment with no dementia. Control of vascular risk factors and treatment of milder forms of disease need to form the focus of preventive strategies.
| References|| |
|1.||Hachinski VC, Bowler JV. Vascular dementia: diagnostic criteria for research studies. Neurology 1993;43:2159-60. [PUBMED] |
|2.||Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, et al . Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000;59:23-30. [PUBMED] |
|3.||Pohjasvaara T, Erkinjuntti T, Vataja R, Kaste M. Dementia three months after stroke: baseline frequency and effect of different definitions of dementia in the Helsinki Stroke Aging Memory Study (SAM) cohort. Stroke 1997;28:785-92. [PUBMED] [FULLTEXT]|
|4.||Tatemichi TK, Desmond DW, Stern Y, et al . Prevalence of dementia after stroke depends on diagnostic criteria. Neurology 1992;42:413. |
|5.||Knopman DS, Parisi JE, Boeve BF, Cha RH, Apaydin H, Salviati A, et al . Vascular dementia in a population-based autopsy study. Arch Neurol 2003;60:569-75. [PUBMED] [FULLTEXT]|
|6.||Roman GC. Vascular dementia may be the most common form of dementia in the elderly. J Neurol Sci 2002;203-204:7-10 |
|7.||Ikeda M, Hokoishi K, Maki N, Nebu A, Tachibana N, Komori K, et al . Increased prevalence of vascular dementia in Japan: a community-based epidemiological study. Neurology 2001;57:839-44. [PUBMED] [FULLTEXT]|
|8.||Lopez OL, Kuller LH, Fitzpatrick A, Ives D, Becker JT, Beauchamp N. Evaluation of dementia in the cardiovascular health cognition study. Neuroepidemiology 2003;22:1-12. |
|9.||Shaji S, Bose S, Verghese A. Prevalence of dementia in an urban population in Kerala, India. Br J Psychiatry 2005;186:136-40. [PUBMED] [FULLTEXT]|
|10.||Desmond DW, Moroney JT, Sano M, Stern Y. Incidence of dementia after ischemic stroke: results of a longitudinal study. Stroke 2002;33:2254-60. [PUBMED] [FULLTEXT]|
|11.||Alladi S. Vascular cognitive impairment. Presented at 4th Asia Pacific Conference Against Stroke, New Delhi March 2007 (unpublished) |
|12.||Reddy SK, Shah B, Varghese C, et al . Responding to the threat of chronic disease in India. Lancet 2005;12:1744-9. |
|13.||Knopman DS, Parisi JE, Boeve BF, Cha RH, Apaydin H, Salviati A, et al . Vascular dementia in a population-based autopsy study. Arch Neurol 2003;60:569-75. |
|14.||Das SK, Bose P, Biswas A, Dutt A, Banerjee TK, Hazra AM, et al . An epidemiologic study of mild cognitive impairment in Kolkata, India. Neurology 2007;68:2019-26. [PUBMED] [FULLTEXT]|
|15.||Erkinjuntti T, Roman G, Gauthier S, Feldman H, Rockwood K. Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke 2004;35:1010-7. |
|16.||Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-36. |
|17.||Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-22. [PUBMED] [FULLTEXT]|
|18.||Pantoni L, Leys D, Fazekas F, Longstreth WT Jr, Inzitari D, Wallin A, et al . Role of white matter Lesions in cognitive impairment of vascular orgin. Alzheimer Dis Assoc Disord 1999;13:S49-54. [PUBMED] |
|19.||Alladi S, Kaul S, Meena AK, Somayajula S, Umadevi M, Reddy JM. Pattern of Vascular Dementia in India: Study of Clinical Features, Imaging and Vascular Mechanisms from a Hospital Dementia Registry. J Stroke Cerebrovasc Dis 2006;15:49-56. [PUBMED] [FULLTEXT]|
|20.||Alladi S, Meena AK, Kaul S, et al . Pattern of vascular cognitive impairment in South India. A clinical and imaging study from a Hospital Dementia Registry Stroke 2004;35:322(ab) |
|21.||Chui H: Dementia due to subcortical ischemic vascular disease. Clin Cornerstone 2001;3:40-51. |
|22.||Looi JC, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests1: Neurology 1999;11;53:670-8. |
|23.||Moorhouse P, Rockwood K. Vascular cognitive impairment: current concepts and clinical developments. Lancet Neurol 2008;7:246-55. [PUBMED] [FULLTEXT]|
|24.||Graham NL, Emery T, Hodges JR. Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia. J Neurol Neurosurg Psychiatry 2004; 75:61-71. [PUBMED] [FULLTEXT]|
|25.||Rockwood K, Moorhouse PK, Song X, MacKnight C, Gauthier S, Kertesz A, et al . Disease pregression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study. J Neurol Sci 2007;252:106-12. [PUBMED] [FULLTEXT]|
|26.||Kalaria RN, Skoog I. Vascular factors in Alzheimer's disease. In: O'Brien J, Ames D, Burns A, editors. Dementia. London: Arnold Press; 2000. p. 505-16. |
|27.||Kalaria RN. The impact of risk factors for stroke on Alzheimer's disease. Neurobiol Aging 2000;21:321-30. [PUBMED] [FULLTEXT]|
|28.||Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al . National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards. Stroke 2006;37:2220-41. [PUBMED] [FULLTEXT]|
|29.||Ingles JL, Wentzel C, Fisk JD, Rockwood K. Neuropsychological Predictors of Incident Dementia in Patients With Vascular Cognitive Impairment, Without Dementia. Stroke 2002;33:1999-2002. [PUBMED] [FULLTEXT]|
|30.||Aharon-Peretz J, Daskovski E, Mashiach T, Kliot D, Tomer R. Progression of dementia associated with lacunar infarctions. Dement Geriatr Cogn Disord 2003;16:71-7. [PUBMED] [FULLTEXT]|
|31.||Aquero-Tores H, Fratiglioni L, Guo Z, Viitanen M, Winblad B. Mortality from dementia in advanced age: a 5 year follow-up study of incident dementia cases. J Clin Epidemiol 1999;52:737-43. |
|32.||Meyer JS, Rogers RL, McClintic K, Mortel KF, Lotfi J. Randomized clinical trial of daily aspirin therapy in multi-infarct dementia. A pilot study. J Am Geriatr Soc 1989;37:549-55. |
|33.||Mintzer JK, Kertesz A, et al . Donepezil in vascular dementia: a randomized, placebocontrolled study. Neurology 2003;61:479-86. |
|34.||Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, et al . The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002;162:2046-52. |
|35.||Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, et al . The Study on Cognition and Prognosis in the Elderly(SCOPE): principal results of a randomised double-blind intervention trial. J Hypertens 2003;21:875-86. [PUBMED] [FULLTEXT]|
|36.||Dufouil C, Ricard F, Fievet N, Dartigues JF, Ritchie K, Tzourio, et al . APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 2005;64:1531-8. |
Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad-500 082
Source of Support: None, Conflict of Interest: None