Cognitive decline is a central component of the dementia process. Population-based prospective studies have confirmed the existence of age-related cognitive decline, although its conceptual basis and nosological status remain controversial. Healthy old people show decline with aging in global cognition and memory function in particular. Preclinical and clinical dementia patients exhibit deficits across multiple cognitive domains, with the largest and most consistent deficits in memory function. Cerebrovascluar disease may lead to cognitive decline and promote the clinical expression of dementia directly or by interaction with APOE η4. Early treatment and prevention of cerebrovascular disease may be the major measures for preventing and postponing the progression of the vascular disease related cognitive decline.

Although vascular dementia was described over a century ago, it remains a difficult and challenging diagnosis. Several sets of clinical criteria have been published in an effort to establish the presence or absence of vascular dementia in a standardized fashion. Clinical studies have demonstrated that they identify different groups of patients and are thus not interchangeable. Retrospective clinicopathological correlations have shown that most are insufficiently sensitive, although they are generally relatively specific. They accurately exclude pure Alzheimer's disease but may include 9% to 39% of mixed dementia cases (Alzheimer's disease and vascular dementia combined). Further studies are needed to develop better performing criteria that could lead to a broad consensus on the clinical diagnosis of vascular and mixed dementia.

There has been a move in recent years to recognize that the most effective treatment for vascular dementia, and for the mixed component of mixed vascular dementia and Alzheimer's disease, lies not in treatment but in prevention. This requires that cases be identified before the onset of vascular damage (a stage termed “brain-at-risk”) or, failing this, as soon as possible but certainly before dementia has developed. These early stages are termed vascular cognitive impairment (VCI). No criteria exist for this early stage of cognitive loss due to cerebrovascular disease and relatively little data exist to indicate how such cases might be identified. The data that do exist suggest that many of the traditional “vascular” features of sudden onset and stepwise progression, etc., are not common in VCI and new criteria will be needed to identify cases. This paper summarizes the data that describe the clinical, neuropsychological, and radiological features that are to be expected in VCI.

In 150 older stroke patients (>75) without dementia, the proportion of people meeting different criteria for early cognitive impairment varied from 17% to 23% depending upon the individual criteria used. Given this large disparity, prospective studies to clarify the utility of different criteria as a predictor of subsequent dementia are a priority.

It is still a challenge to identify typical features of cognitive function in vascular dementia (VaD) in clinical as well as in preclinical stages. Selective empirical findings are described to illuminate degrees of cognitive decline. In predementia stages, speeded performance (motor and mental) and executive functions may be affected as demonstrated by CADASIL subjects and stroke survivors. In dementia stages, motor and mental speed as well as executive functions is commonly affected in addition to typical cognitive dysfunction in dementia (memory, verbal, and visuospatial). To summarize characteristics during preclinical and clinical stages, VaD appears to be associated with impairment in motor and mental speed as well as in executive function.

Noncognitive or behavioral and psychological symptoms (BPSD) are common in vascular dementia. Many occur with the same frequency as in Alzheimer's disease, though depression, emotional lability, and apathy may be more common and psychosis less so. There is a particularly strong relationship between cerebrovascular disease and depression.

Hypertension is a risk factor for stroke, ischemic white-matter lesions, cardiovascular disorders, and vascular dementia. This risk increases with increasing blood pressure. Several studies report that high blood pressure precedes Alzheimer's disease (AD) by decades, but blood pressure decreases the years before dementia onset and is lower in individuals with AD than in controls. High blood pressure has also been related to the neuropathological manifestations of AD. The exact mechanism behind these associations is not clear. Hypertension may cause cerebrovascular disease that may increase the likelihood that individuals with AD encephalopathy will express a dementia syndrome, this may accelerate the AD process, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Even if hypertension results only in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of individuals with dementia.

Multiple epidemiological and brain imaging studies show a strong association between elevations in systolic blood pressure and lesions of cerebral white matter. The association between white-matter lesions and systolic blood pressure persists even if individuals are receiving treatment, suggesting that these individuals may be undertreated. In addition, these studies suggest that lesions of cerebral white matter may serve as markers for atherosclerotic vascular disease. Treatment strategies, therefore, should focus on early and aggressive management of elevated blood pressure, but definitions of elevated blood pressure may need to be revised downward to achieve best results.

A pivotal role for cholesterol influence on production of the putative AD toxin, amyloid β (Aβ), has been amply demonstrated. More importantly, this relationship has consistently been identified in both in vivo and in vitro studies. Lowering cholesterol levels has been shown to cause a beneficial effect on Aβ levels in animal models, and epidemiological data indicate a beneficial effect on the risk of AD with prior statin use. Blinded, placebo-controlled clinical investigations assessing the benefit of statins on cognitive indices in mild to moderate AD are ongoing and one will be reported on soon. A prospective study assessing the effect of statin use on the risk of AD is under way as an observational component of a placebo-controlled primary prevention trial testing anti-inflammatory agents. Nevertheless, the foregoing suggests that routine monitoring and intervention for elevated cholesterol levels among the elderly could promote more than a healthy heart.

The treatment of patients with acute stroke is reviewed. Evidence of the existence of an ischemic penumbra in humans is presented. Different approaches to treatment of acute stroke include restoring blood flow by thrombolysis, neuroprotection, and early secondary prevention with aspirin. The evidence for each of these approaches is reviewed. Organization of stroke services, and particularly the use of stroke units, have been shown to significantly improve stroke outcome and these data are presented.

Stroke recurrence can be reduced substantially by intervention with the appropriate stroke preventive(s). Control of blood pressure, use of one of the antiplatelet agents aspirin, aspirin plus extended (modified)-release dipyridamole, or clopidogrel, administration of warfarin for patients with atrial fibrillation and high-risk profiles for stroke, and use of carotid endarterectomy in patients with high grades of symptomatic carotid artery stenosis are all proven therapies for prevention of stroke recurrence. Newer therapies to reduce the risk of infection and inflammation promise to further reduce the risk of first and recurrent stroke and are undergoing testing. In this article we review standard and more novel means to prevent stroke recurrence.

A three-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides the first information on the rate, clinical predictors, and cognitive consequences of MRI white-matter lesions in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white-matter hyperintensities at baseline were the only significant predictors of white-matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.

The therapy for vascular dementia has known several changes and updates since the use of niacin in the first years of the 20th century. These modifications were due to the parallel evolution of the concept of vascular dementia. Initially, treatments in this area were proposed because they were considered vasoactive and able to increase the blood flow of the brain. After these, other drugs were introduced because they were also able to ameliorate the oxygen usage by the suffering neurons. The more recent therapeutic proposals were made for drugs active on the metabolic activities of the brain, or with hemorrheological or antioxidant properties. As a consequence, a large array of different pharmacological properties were considered in proposing the several different kinds of drugs as useful in vascular dementia patients. The most recent attempt in this field consists of evaluating the usefulness of traditional antidementia drugs (those with anticholinesterase action) in patients with a prevalence of cerebrovascular disorders.