Vascular Contributions to Cognitive Impairment and Dementia

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Background and Purpose -- This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment.

Methods -- Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee.

Results -- The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury -- not solely stroke -- ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular unit and mechanisms regulating cerebral blood flow are likely to be important components of the pathophysiological processes underlying VCI. Cerebral amyloid angiopathy is emerging as an important marker of risk for Alzheimer disease, microinfarction, microhemorrhage and macrohemorrhage of the brain, and VCI. The neuropathology of cognitive impairment in later life is often a mixture of Alzheimer disease and microvascular brain damage, which may overlap and synergize to heighten the risk of cognitive impairment. In this regard, magnetic resonance imaging and other neuroimaging techniques play an important role in the definition and detection of VCI and provide evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common. In many cases, risk markers for VCI are the same as traditional risk factors for stroke. These risks may include but are not limited to atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia. Furthermore, these same vascular risk factors may be risk markers for Alzheimer disease. Carotid intimal-medial thickness and arterial stiffness are emerging as markers of arterial aging and may serve as risk markers for VCI. Currently, no specific treatments for VCI have been approved by the US Food and Drug Administration. However, detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of VCI, even in older people.

Conclusions -- Vascular contributions to cognitive impairment and dementia are important. Understanding of VCI has evolved substantially in recent years, based on preclinical, neuropathologic, neuroimaging, physiological, and epidemiological studies. Transdisciplinary, translational, and transactional approaches are recommended to further our understanding of this entity and to better characterize its neuropsychological profile. There is a need for prospective, quantitative, clinical-pathological-neuroimaging studies to improve knowledge of the pathological basis of neuroimaging change and the complex interplay between vascular and Alzheimer disease pathologies in the evolution of clinical VCI and Alzheimer disease. Long-term vascular risk marker interventional studies beginning as early as midlife may be required to prevent or postpone the onset of VCI and Alzheimer disease. Studies of intensive reduction of vascular risk factors in high-risk groups are another important avenue of research.


Key Words:

AHA Scientific Statements
vascular dementia
Alzheimer disease
risk factors
prevention
treatment

Gorelick PB, Scuteri A, Black SE, et al. Vascular Contributions to Cognitive Impairment and Dementia. Stroke. 2011; 42: 2672-2713.


For full paper, go to: http://stroke.ahajournals.org/content/42/9/2672.full

Table of Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2674

Defining Alzheimer Disease and VCI . . . . . . . . . .2676

2.1. Evolution of the Terminology. . . . . . . . . . . . .2676

2.2. Clinical Criteria for the Diagnosis of VaD . . .2677

2.3. Heterogeneity of the VaD Syndrome . . . . . . .2677

2.4. Mild VCI. . . . . . . . . . . . . . . . . . . . . . . . . . . .2677

2.5. Reversibility of VaMCI . . . . . . . . . . . . . . . . .2679

2.6. Neuropsychological Assessments of VCI . . . .2679

2.7. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2679

Neuropathological Aspects. . . . . . . . . . . . . . . . . . .2679

3.1. Cerebral Infarctions Are Very Common in Older People. . . . . . . . . . . . . . . . . . . . . . . .2679

3.2. Cerebral Infarctions and VCI . . . . . . . . . . . . .2679

3.3. Relation of Infarcts to Alzheimer Disease Pathology and Dementia. . . . . . . . . . . . . . . . .2680

3.4. Relation of Infarcts to Alzheimer Disease Pathology and MCI . . . . . . . . . . . . . . . . . . . .2680

3.5. Other Vascular Pathologies. . . . . . . . . . . . . . .2680

3.6. Neuroimaging and Pathology: Future Directions. . . . . . . . . . . . . . . . . . . . . . . . . . . .2680

3.7. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2681

Basic Science Aspects: Importance of the Neurovascular Unit and Cerebral Blood Flow . . . .2681

4.1. The Neurovascular Unit and Brain Homeostasis . . . . . . . . . . . . . . . . . . . . .2681

4.2. The Neurovascular Unit: A Target of Vascular and Neurodegenerative Dementias . . . . . . . . .2681

4.3. Mechanisms of Neurovascular Dysfunction: Role of Oxidative Stress and Inflammation . .2681

4.4. Animal Models of VCI. . . . . . . . . . . . . . . . . .2682

4.5. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2682

Cerebral Amyloid Angiopathy and Hereditary Small-Vessel Syndromes . . . . . . . . . . . . . . . . . . . .2682

5.1. Cerebral Amyloid Angiopathy and Vascular Effects of Aβ . . . . . . . . . . . . . . . . . . . . . . . . . .2682

5.2. Hereditary Small-Vessel Syndromes. . . . . . . .2683

5.3. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2683

5.4. Recommendations. . . . . . . . . . . . . . . . . . . . . .2683

Pathophysiology of Arterial Structure and Function. . . .2683

6.1. Carotid Intima-Media Thickness and VCI . . .2684

6.2. Arterial Stiffness and VCI . . . . . . . . . . . . . . .2684

6.3. Small-Artery Remodeling and VCI. . . . . . . . .2684

6.4. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2685

Neuroimaging Factors That May Influence the Clinical Presentation and Course of VCI . . . . . . . .2685

7.1. Clinical Presentation and Importance of Neuroimaging Studies. . . . . . . . . . . . . . . . . . .2685

7.2. Prevalence of CVBI and Associated Cognitive Findings. . . . . . . . . . . . . . . . . . . . .2685

7.3. Poststroke Dementia. . . . . . . . . . . . . . . . . . . .2686

7.4. CVBI and Cognition in Convenience Samples . . .2686

7.5. Depression on a Cerebrovascular Basis and CVBI. . . . . . . . . . . . . . . . . . . . . . . . . . . .2686

7.6. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . .2686

7.7. Recommendation . . . . . . . . . . . . . . . . . . . . . .2687

Impact of Cardiovascular Risk Factors at Different Ages on the Risk of Cognitive Decline . . . . . . . . .2687

8.1. Nonmodifiable Risk Factors . . . . . . . . . . . . . .2687

8.1.1. Demographic Factors . . . . . . . . . . . . . .2687

8.1.2. Genetic Factors. . . . . . . . . . . . . . . . . . .2687

8.1.3. Summary: Demographic and Genetic Factors . . . . . . . . . . . . . . . . . . . . . . . . .2687

8.2. Lifestyle Factors. . . . . . . . . . . . . . . . . . . . . . .2687

8.2.1. Education. . . . . . . . . . . . . . . . . . . . . . .2687

8.2.2. Diet . . . . . . . . . . . . . . . . . . . . . . . . . . .2688

8.2.3. Physical Activity and Physical Function . .2688

8.2.4. Alcohol Intake. . . . . . . . . . . . . . . . . . .2688

8.2.5. Obesity. . . . . . . . . . . . . . . . . . . . . . . . .2688

8.2.6. Smoking. . . . . . . . . . . . . . . . . . . . . . . .2689

8.2.7. Social Support/Networks . . . . . . . . . . .2689

8.2.8. Summary: Lifestyle Factors . . . . . . . . .2689

8.2.9. Recommendations. . . . . . . . . . . . . . . . .2689

8.3. Depression . . . . . . . . . . . . . . . . . . . . . . . . . . .2689

8.4. Physiological Risk Factors . . . . . . . . . . . . . . .2689

8.4.1. Blood Pressure. . . . . . . . . . . . . . . . . . .2689

8.4.2. Hyperglycemia, Insulin Resistance, Metabolic Syndrome, and Diabetes . . .2689

8.4.3. Lipids. . . . . . . . . . . . . . . . . . . . . . . . . .2689

8.4.4. Inflammation . . . . . . . . . . . . . . . . . . . .2690

8.4.5. Summary: Physiological Risk Factors . . .2690

8.4.6. Recommendations. . . . . . . . . . . . . . . . .2690

Concomitant Clinical Vascular Disease . . . . . . . . .2690

9.1. Coronary Artery Disease . . . . . . . . . . . . . . . .2690

9.2. Stroke. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2690

9.3. Chronic Kidney Disease. . . . . . . . . . . . . . . . .2690

9.4. Atrial Fibrillation. . . . . . . . . . . . . . . . . . . . . .2690

9.5. Peripheral Arterial Disease . . . . . . . . . . . . . . .2690

9.6. Low Cardiac Output. . . . . . . . . . . . . . . . . . . .2690

9.7. Summary: Concomitant Disease . . . . . . . . . . .2690

Clinical Trials in VCI and Symptomatic Treatment. . . .2691

10.1. Background. . . . . . . . . . . . . . . . . . . . . . . . . .2691

10.2. Pharmacological Treatment of Cognitive Impairment . . . . . . . . . . . . . . . . . . . . . . . . . .2691

10.3. Summary and Recommendations: Pharmacological Therapy . . . . . . . . . . . . . . .2692

10.3.1. Summary . . . . . . . . . . . . . . . . . . . . .2692

10.3.2. Recommendations. . . . . . . . . . . . . . .2692

10.4. Nonpharmacological Treatments . . . . . . . . . .2692

10.4.1. Summary . . . . . . . . . . . . . . . . . . . . .2692

Prospects for Prevention of VCI and Alzheimer Disease by Risk Factor Control . . . . . . . . . . . . . . .2692

11.1. Public Health Aspects. . . . . . . . . . . . . . . . . .2692

11.2. Results of Main Studies on Vascular Factor Control and Prevention of Dementia . . . . . . .2692

11.2.1. Hypertension. . . . . . . . . . . . . . . . . . .2692

11.2.1.1. Observational Studies on Antihypertensive Drugs and Risk of Dementia . . . .2692

11.3. Clinical Trials of Blood Pressure–Lowering Drugs and Risk of Dementia. . . . . . . . . . . . .2694

11.3.1. Individual Trials. . . . . . . . . . . . . . . .2694

11.3.2. Meta-Analyses . . . . . . . . . . . . . . . . .2696

11.3.3. Ongoing or Planned Trials . . . . . . . .2696

11.3.4. Summary and Recommendations: Blood Pressure Lowering and Cognition . . . . .2696

11.3.4.1. Summary. . . . . . . . . . . . . .2696

11.3.4.2. Recommendations . . . . . . .2696

11.4. Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . .2696

11.4.1. Summary and Recommendation: Diabetes . . . . . . . . . . . . . . . . . . . . . .2697

11.5. Lipids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2697

11.5.1. Summary and Recommendation: Lipids . . . . . . . . . . . . . . . . . . . . . . . .2697

11.6. Other Interventions for Vascular Factors. . . .2697

11.6.1. Antiaggregants . . . . . . . . . . . . . . . . .2697

11.6.2. Lifestyle. . . . . . . . . . . . . . . . . . . . . .2698

11.6.3. Vitamin Supplements . . . . . . . . . . . .2698

11.6.4. Summary and Recommendations: Other Interventions. . . . . . . . . . . . . .2698

Summary and Course of Action. . . . . . . . . . . . . . .2698

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2701