Defending the Guidelines Vascular Burden of Cognitive Impairment & Dementia

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1 Defending the Guidelines Vascular Burden of Cognitive Impairment & Dementia Philip B. Gorelick, MD MPH FACP Medical Director Hauenstein Neuroscience Center St. Mary s Health Care Grand Rapids, Michigan Feb. 3, 2012, New Orleans, ISC, ~10 minutes

2 Disclosure Relevant to this Presentation None

3 Objectives In relation to the vascular contributions to cognitive impairment & dementia, you will be able to discuss: 1. Rationale for the AHA/ASA guidance statement 2. Key recommendations 3. Next steps

4 Gorelick PB, Scuteri A, Black SE, et al. Stroke 2011; 42:

5 Vascular Contributions to Cognitive Impairment & Dementia: Methods-1 Purpose: to provide an overview of the evidence on vascular contributions to cognitive impairment & dementia Methods: 1. Creation of an Expert Panel 2. Joint collaboration between AHA Stroke & Epidemiology & Prevention Councils 3. Systematic literature reviews covering publications from 1990 to May 1, 2010, previously published guidelines, personal files & expert opinion to summarize existent evidence, gaps in current knowledge & recommendations Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

6 Table of Contents-1 1. Introduction 2. Defining Alzheimer Disease & VCI 3. Neuropathological Aspects 4. Basic Science Aspects: Neurovascular Unit, Neurovascular Dysfunction & Animal Models 5. Cerebral Amyloid Angiopathy & Hereditary Small-Vessel Syndromes 6. Pathophysiology of Arterial Structure & Function: Carotid IMT, Arterial Stiffness & Small-Artery Remodeling Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

7 Table of Contents-2 7. Neuroimaging Factors 8. Impact of Cardiovascular Risk Factors at Different Ages on the Risk of Cognitive Decline: Demographic, Genetic, Lifestyle, Depression, Physiological (Blood Pressure, Hyperglycemia etc., Lipids, Inflammation) 9. Concomitant Clinical Vascular Disease: CAD, Stroke, CKD, AF, Low Cardiac Output 10. Clinical Trials & Symptomatic Treatment 11. Prospects for Prevention of VCI & Alzheimer Disease by Risk Factor Control 12. Summary & Course of Action Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

8 Rationale for the AHA/ASA Guidance Statement Vascular Contributions to Cognitive Impairment & Dementia Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

9 Why the Need for This AHA/ASA Guidance Statement? 1. Occurrence of stroke and vascular risk factors are common as we age 2. Vascular risk factors have been linked to vascular cognitive impairment (VCI) & Alzheimer s disease (AD) 3. VCI & AD are common forms of cognitive impairment 3. An evidence-based review is needed to guide health care professionals on management of these vascular factors in the possible prevention and treatment of cognitive impairment Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

10 Complex Web of Causation: Cognitive Impairment & Neurovascular Unit A-beta Potent vasoconstrictor CADASIL Amyloid angiopathy Oxidative stress Genetic defects Risk factors Inflammation Hypertension Diabetes Aging Impair endothelial responses in cerebral microcirc. & blunted functional hyperemia (neuronal activity increases CBF) In Alzheimer Dis. Hypercontractile Vessels Microglia Neurovascular dysfunction Demyelination/Hyp ermetabolism Neuron Cerebral Arteriole Hypoxia ischemia Astrocyte BBB alteration Oligo precursors/rep -air potential Other Vasc Associations -Retinal narrowing, arterial stiffness & small vessel disease -Aortic stiffness & microvascular brain damage -Carotid intimal media thickness White matter damage Bystander damage Brain atrophy Increased stroke risk, poor outcome Vascular cognitive impairment Alzheimer s dementia Iadecola, Acta. Neuropath. Sept. 2010

11 Common Genetic and Environmental Risk Factors for AD and Atherosclerosis Epidemiological Factor ApoEe4 polymorphism Hypercholesterolemia Hypertension Hyperhomocysteinemia Diabetes mellitus Metabolic syndrome Smoking Systemic inflammation Increased fat intake and obesity Source: Casserly I, Topol E. Lancet 2004; 363:

12 Illustrative Example of Role of Vascular Risk Factors in AD Midlife vascular risk factors and role in AD BMI>30 SBP>140 mm Hg Cholesterol> 251mg/dL Odds ratio for each factor on risk of AD Approximately 2 fold Odds ratio for all 3 factors on risk of AD Approximately 6 fold AD= Alzheimer disease BMI= body mass index SBP= systolic blood pressure Source: Kivipelto M et al. Arch Neurol 2005; 62: (also cited in Michel J-P et al. JAMA 2008; 299: )

13 Key Recommendations Vascular Contributions to Cognitive Impairment & Dementia Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

14 Lifestyle Factor Recommendations The following lifestyle intervention in persons at risk for VCI is reasonable: 1. Smoking cessation (Class IIa, Level of Evidence A) 2011 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.

15 Lifestyle Factor Recommendations The following lifestyle interventions in persons at risk for VCI may be reasonable: 1. Moderation of alcohol intake (Class IIb, Level of Evidence B) 2.Weight Control (Class Ilb, Level of Evidence B) 3.Physical Activity (Class IIb, Level of Evidence B) The following is not recommended: The use of antioxidants and B vitamins in persons at risk for VCI are not useful based on current evidence ( Class III, Level of Evidence A) 2011 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.

16 Physiologic Risk Factors VCI Treatment Recommendations Treatment of the following physiologic factor in persons at risk for VCI is recommended: Hypertension (Class I, Level of Evidence A) Treatment of the following physiologic factors in persons at risk for VCI may be reasonable: Hyperglycemia (Class IIb, Level of Evidence C) Hypercholesterolemia (Class IIb, Level of Evidence A) It is uncertain if treatment of inflammation will reduce the risk of VCI in persons at risk of VCI. (Class IIb, Level of Evidence C) Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.

17 Recommendations Regarding Blood Pressure Lowering and Cognition 1. In patients with stroke, lowering blood pressure is effective for reducing the risk of post-stroke dementia (Class I, Level of Evidence: B) 2. There is reasonable evidence that, in middleaged and young-elderly, lowering blood pressure can be useful for the prevention of late-life dementia (Class IIa, Level of Evidence: B) 3. The usefulness of lowering blood pressure in individuals age 80+ is not well-established (Class IIb, Level of Evidence: B) 2011 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

18 Other Interventions on Vascular Factors: Recommendations 1. A Mediterranean-type dietary pattern has been associated with less cognitive decline in several studies and may be reasonable (Class IIb, Level of Evidence B). 2. Vitamin supplementation is not proven to improve cognitive function, even if homocysteine levels have been positively influenced, and its usefulness is not well established. (Class IIb, Level of Evidence B). 3. Physical activity might be considered for the prevention of cognitive impairment (Class IIb, Level of Evidence B), but the usefulness of other lifestyle or vitamin interventions are uncertain (Class IIb, Level of Evidence B). 4. Effectiveness of antiaggregant therapy for VCI is not well established (Class IIb, Level of Evidence B) American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.

19 National Institute of Health State-of-the- Science Conference Statement on Preventing AD & Cognitive Decline-4 Conclusions 1. No association of even moderate evidence that a modifiable risk factor reduced risk of AD 2. Most studies showed no association, inconclusive evidence & quality of evidence was generally low 3. Evidence inadequate to conclude any therapeutic intervention delayed onset of AD 4. RCTs had not identified positive treatment benefits 5. Inconsistent & varied methodological assessments prevented clear & concise answers to questions 6. These gaps need to be bridged Source: Daviglus ML et al Ann Intern Med 2010; 153:

20 Next Steps in Research Vascular Contributions to Cognitive Impairment & Dementia Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

21 Research Agenda 1. Develop & validate practicable cognitive batteries 2. Pursue novel neuroimaging methods to identify biomarkers & risks for CVBI 3. Longitudinal clinical-neuropathological & neuroradiological studies 4. Centers of excellence for study of CVBI 5. RCTs targeting vascular risk factors 6. Preclinical and clinical studies of aging of arteries & neurovascular unit 7. Identify novel risk markers for CVBI 8. Search for genetic & other novel factors for prevention CVBI= cerebral vascular brain injury RCTs= randomized controlled trials Source: Gorelick PB, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:

22 Summary Vascular cognitive impairment (VCI) may occur when there is clinical or subclinical cerebral vascular brain injury (CVBI) Clinical and subclinical CVBI may lead to VCI via strategically placed small and large brain strokes and white matter lesions (leukoaraiosis) Cardiovascular risks such as hypertension and other factors are linked not only to VCI risk but also to Alzheimer s disease risk Blood pressure lowering is recommended in persons at risk for VCI prevention

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