Can Vascular Cognitive Impairment Be Prevented?
Philip B. Gorelick, MD, MPH
Rush Medical College
Chicago, IL, USA

A wide range of epidemiologic and other studies indicate that four risk factors for cardiovascular disease---hypertension, abnormalities in glucose and insulin levels, cigarette smoking, and obesity--- are also risk factors for vascular cognitive impairment and dementia. Hypertension (particularly high systolic blood pressure) appears to be the strongest predictor of significant cognitive impairment in the elderly. Dr. Gorelick reviewed the literature and explained a possible mechanism for cerebral neurotoxicity through primary disruption of endothelium in the brain’s blood vessels. As a conclusion, he stressed the importance of diagnosing and treating hypertension. Aggressive midlife medical care for cardiovascular disease may have significant benefits in decreasing the risk for late-life vascular cognitive impairment and dementia.

Dr. Gorelick opened by noting that studies have suggested certain genetic and clinical characteristics are associated with healthy aging. For instance, there may be roughly 1000 genes associated with longevity, with at least one major gene localized to chromosome 4. There are multiple clinical characteristics shared by those who live long and in good health. Four such traits are low blood pressure, low serum glucose, no cigarette smoking, and no obesity.

When viewed differently, it is clear that risk factors for cardiovascular disease --- hypertension, abnormal glucose and insulin levels, cigarette smoking, and obesity --- are also risk factors for cognitive health in late life. Based on data from numerous studies, hypertension, especially elevated systolic blood pressure, appears to be the strongest predictor of vascular cognitive impairment and dementia among the elderly.

Older research uses the model of vascular dementia to understand pathologic cognitive declines. Imaging and etiologic studies of patients with vascular dementia identify subtypes such as multi-infarct dementia, as well as dementia associated with a strategically important infarct (often involving the angular gyrus or thalamus) or dementia associated with diffuse subcortical damage.

Over time, the model has shifted to one of vascular cognitive impairment characterized by a combination of etiologic and clinical traits. Vascular cognitive impairment is actually a spectrum of syndromes that have decreased cognitive ability across multiple domains at their centers. Impairment can range from slight to severe, and the time course ranges from sudden to subacute to slow development and progression.

Multiple direct causes have been identified, including clinical and silent strokes. Pathologic findings include microvascular disease, large-artery disease, deposition of A-beta peptide, or cerebral hemorrhage. Vascular cognitive impairment embraces a variety of heterogeneous syndromes, and distinction from Alzheimer’s dementia and direct stroke effect, both common in the elderly, complicates the research and clinical picture.

Gorelick restated the research and clinical problem from the public health perspective: ‘Can you identify early-phase vascular cognitive impairment and intervene to prevent dementia?’ He believes the answer is ‘Yes.’ He noted epidemiologic studies suggesting that roughly half of people with cognitive impairment but no dementia develop dementia in five years, which suggests there may be a target for preventive intervention. A twin study showed that the twin with higher midlife systolic blood pressure, metabolic abnormalities involving glucose and/or insulin levels, or both was at higher risk for late-life dementia.


Population Attributable Risk (PAR)
of Select Modifiable Stroke Risk Factors
for Vascular Cognitive Impairment



Factor
Relative Risk
Prevalence
PAR
Hypertension
8.7
25%
66%
Diabetes mellitus
1.8
10%
8%
LDL-cholesterol
2.6
36%
37%
Atrial fibrillation
1.5
4%
2%
Current cigarette smoker
1.8
25%
17%
Alcohol:
2-5 drinks/day
1.8
7%
5%

     Source: Gorelick P, 2003


He moved from an understanding of vascular cognitive impairment and dementia and their risk factors to study of possible mechanisms through which risk factors might contribute to clinically evident cognitive decline.

He presented findings from a 2003 paper on Alzheimer’s disease and microvascular angiogenesis to frame the hypothesis that cerebrovascular damage (specifically, disruption of the endothelium and its action as a blood-brain barrier) can lead to neurotoxic effects through a combination of soluble factors and deposition of beta-amyloid protein.

Neurotoxicity may be evident clinically as Alzheimer’s disease or as vascular cognitive impairment or nonAlzheimer’s dementia.

Gorelick placed studies that did not find a link between risk factors, especially hypertension, and cerebrovascular disease and dementia in context by emphasizing that blood pressure is known to decrease as cognitive impairment worsens. He believes some studies may have missed a link between hypertension and vascular cognitive impairment by evaluating people too late in the course of their clinical presentation.

Gorelick concluded that research work as varied as epidemiologic studies on healthy aging to anatomic and molecular work on dementia lead to the same conclusion: Control of vascular risk factors by midlife can decrease the risk for vascular cognitive impairment and dementia at the end of the lifespan. Hypertension is probably the most important target for such intervention.

 

Reporter: Elizabeth Coolidge-Stolz