치매예방을위한만성질환관리전략 김광일 서울대학교의과대학내과학교실 분당서울대학교병원내과
A sharp rise in the death rate from Alzheimer s disease Ivan Casserly & Eric Topol, Lancet 2004
Potential for primary prevention of Alzheimer s disease Alzheimer s disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. Norton S et al. Lancet Neurology 2014
Decrease of age-specific dementia prevalence in UK CFAS=Cognitive Function and Ageing Study. CFAS I 1989~1994, CFAS II 2008~2011 Matthews FE et al. Lancet 2013
Dementia Dementia is an acquired syndrome in which impairment of cognitive abilities is severe enough to interfere with the individual s customary occupational and social activities. Loss of memory and one or more other cognitive impairment Substantial impairment in social or occupational functioning Thus the term dementia is useful to communicate the presence of a syndrome but should not be used as a synonym for any particular diagnostic category, such as Alzheimer s disease (AD)
Classification of dementia Other (AD + CVD, Lewy Body, FTD, unknown) 30.5% Vascular Dementia 15.8% Alzheimer's Dementia 53.7% Lobo A et al. Neurology 2000
Jan A. Staessen, Hypertension. 2007;49:389-400 Time course of cognitive functions
Jan A. Staessen, Hypertension. 2007;49:389-400 Overlap between AD & VaD
Dysregulation of brain blood vessels in Alzheimer s disease Costantino Iadecola, Nat Med 2005
Heart brain connection in ageing & cognitive decline Qiu & Fratiglioni, Nat Rev Cardiol 2015
Hypertension
Hypertension, Stroke, and Dementia Iadecola & Davisson, Cell metabolism 2008
Ischemic brain lesions associated with hypertension Faraco & Iadecola, HT 2013
Effect of hypertension on cerebral blood vessels Faraco & Iadecola, HT 2013
Blood pressure & cognitive impairment Qiu et al, Lancet Neurol 2005
Skoog I, et al, Lancet 1996
Midlife Hypertension and 20-Year Cognitive Change Gottesman et al, Lancet Neurology 2014
Different BP lowering effect; Stroke vs CAD Cerebrovascular disease Coronary artery disease
Geographic distribution of relative disease burden from stroke & IHD Kim et al, Circulation 2011
Treatment of hypertension & prevention of cognitive impairment : SYST-EUR 9 Alzheimer Disease Mixed or Vascular Dementia Rate (/ 1000 patients-years) 6 3 55% 0 Control Group Active Group Staesson JA, et al. Lancet 1997;350:757 764.
Effect of antihypertensive treatment on the incidence of all-cause dementia Marpillat, et al, J HT 2013
Comparisons of the effects of anti-hypertensive drug class on cognition Marpillat, et al, J HT 2013
Renin angiotensin system & APP metabolism Kehoe & Wilcock, Lancet Neurol 2007; 6: 373 78
Cerebral blood flow; Range of autoregulation Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004)
Increased pulse pressure linked to dementia: HYVET Peters et al, J Hypertens 2012
40-Month Decline in Total Brain Volume in the Blood Pressure Trials Williamson et al, JAMA IM 2014
Putative pathways linking elevated blood pressure to brain aging Tzourio et al, HT 2014
Conclusions regarding age-dependent blood pressure, cognitive function, & dementia 1. High blood pressure in midlife is a risk for dementia or cognitive decline in later life 2. Elevated blood pressure (eg, systolic blood pressure >180 mm Hg) in elderly adults may be a risk for dementia 3. Low diastolic blood pressure (eg, <70 mm Hg) in older adults is associated with increased dementia risk 4. Elevated blood pressure in mid-life and low blood pressure in later life may be associated with Alzheimer s disease
American Heart Association/American Stroke Association blood pressure lowering guidance for practicing health care providers as it pertains to VCI 1. Reduction of blood pressure according to standard guidelines (eg, JNC 7) reduces the risk of stroke, myocardial infarction and other major cardiovascular outcomes 2. For persons at risk of developing VCI, treatment of blood pressure is recommended according to standard guidelines to prevent VCI 3. For persons with a history of stroke, lowering blood pressure is effective for reducing the risk of post-stroke dementia 4. For middle-age persons and the young-elderly, lowering blood pressure can be useful for the prevention of late-life dementia 5. For persons >80 years, the usefulness of blood pressure lowering for the prevention of dementia is not well established
Diabetes
Pathophysiologicalmechanisms linking diabetes to changes in the brain and dementia Biessels et al. Lancet Neurology 2006
Glucose Levels and Risk of Dementia Paul K. Crane et al. NEJM 2013
Association Between Hypoglycemia and Dementia Dementia risk Hypoglycemia risk Yaffe et al. Health ABC, JAMA IM 2013
Lancet Diabetes Endocrinol 2014 ADA 2014
Diabetes drugs & neurological disorders Patrone et al. Lancet Diabetes Endocrinol 2014
Dyslipidemia
Cholesterol & All-cause mortality in elderly Honolulu Heart Program, Lancet 2001
Effect of lipid-lowering treatment on stroke Lancet Neurol 2004; 3: 271 78
SPARCL: High-dose statin treatment reduces fatal/nonfatal stroke Primary outcome (Fatal & Non-fatal Stroke) 16 12 16% RRR* HR 0.84 (0.71 0.99) P = 0.03 Placebo NNT = 46 patients for 5 years Fatal/ nonfatal stroke (%) 8 4 Atorvastatin 0 0 1 2 3 4 5 6 Time since randomization (years) *Adjusted SPARCL Investigators. N Engl J Med. 2006;355:549-59.
Serum Cholesterol Levels & Cerebral Amyloidosis Bruce Reed et al. JAMA Neurol 2014
Statins& Cognitive Function Ann Int Med 2013 Meta-analyses of risk ratios from cohort studies for dementia, Alzheimer disease, and mild cognitive impairment
Menge et al, Nat Rev Neurosci 2005 Effects of statins in Alzheimer s disease
Statin use & cognitive function (RCT) Miidaa, Curr Opin Lipidol 16:619 623. 2005
A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease Sano et al. Neurology 2011
Cardiovascular drug: potential therapeutic benefit in AD Ivan Casserly, Eric Topol, Lancet 2004; 363: 1139 46
Effects of Secondary Prevention on Cognitive Function in Stroke Patients Douiri et al, Circulation 2013
The sooner, the better