ReviewThe projected effect of risk factor reduction on Alzheimer's disease prevalence
Introduction
Alzheimer's disease (AD) is the most common cause of dementia, accounting for 60–80% of cases, although there is growing awareness that AD is often mixed with other dementia causes. By linear extrapolation of estimates from 2006,1 about 33·9 million people worldwide have AD at present, and according to estimates from the Alzheimer's Association,2 5·3 million people in the USA have the disease. Prevalence is anticipated to triple over the next 40 years owing to demographic changes and longer life expectancies.1, 2 Available drugs for dementia and AD have small effect sizes and do not clearly alter disease progression,3 and several promising new drugs have recently failed in phase 3 clinical trials.4, 5 Given the current absence of disease-modifying treatments, as well as increasing awareness that symptoms develop over many years or even decades, there has been growing interest in identification of effective strategies for prevention of AD. Delaying symptom onset by as little as 1 year could potentially lower AD prevalence by more than 9 million cases over the next 40 years.1
Observational studies have identified a wide range of potentially modifiable risk factors for AD and dementia, including cardiovascular risk factors (eg, hypertension, diabetes, and obesity), psychosocial factors (eg, depression), and health behaviours (eg, low level of physical or mental activity and smoking).6 However, few randomised controlled trials (RCTs) have examined the effect of risk factor modification on AD prevalence and even fewer have investigated several factors at once.
The aim of this Review was to provide an updated summary of the evidence related to several potentially modifiable risk factors for AD and to project the effect of risk factor reduction on AD prevalence by calculating population attributable risks (PARs), which take into account the prevalence of a given risk factor as well as the strength of its association with the outcome of interest. PAR estimates are important because they can help identify the intervention strategies that are likely to result in the greatest effect on disease prevalence.7
Section snippets
Search strategy and selection criteria
In 2010, the US National Institutes of Health published an independent state-of-the-science report that included a comprehensive systematic review of the evidence related to risk factors for AD and cognitive decline.6 Although the report highlighted many limitations of the available evidence, several potentially modifiable factors were identified as being associated with increased risk of cognitive decline or AD, or both. The factors with the most consistent evidence included diabetes mellitus,
Relative risk for AD
Diabetes has been associated with an increased risk of AD and dementia in several studies.15, 16, 17 A meta-analysis by Lu and colleagues18 identified eight prospective, population-based studies that have examined the association between diabetes mellitus and risk of AD, vascular dementia, and all-cause dementia. For AD, two studies reported a statistically significant increase in AD risk in patients with diabetes whereas five studies noted a non-significant increase, resulting in a combined RR
Discussion
Our findings suggest that up to half of AD cases are potentially attributable to modifiable risk factors. Furthermore, we expect that these findings will be similar for all-cause dementia. Our Review focused on AD because most of the meta-analyses we identified focused on AD. However, AD contributes to most cases of dementia, and risk factors for AD and all-cause dementia are generally similar. Therefore, attributable-risk estimates for all-cause dementia are probably similar to the estimates
References (101)
- et al.
Forecasting the global burden of Alzheimer's disease
Alzheimers Dement
(2007) - et al.
Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders
Biol Psychiatry
(2010) - et al.
Risk of dementia in diabetes mellitus: a systematic review
Lancet Neurol
(2006) - et al.
Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review
Eur J Pharmacol
(2008) - et al.
Global estimates of the prevalence of diabetes for 2010 and 2030
Diabetes Res Clin Pract
(2010) - et al.
The age-dependent relation of blood pressure to cognitive function and dementia
Lancet Neurol
(2005) - et al.
Blood pressure and the risk for dementia: a double edged sword
Ageing Res Rev
(2009) - et al.
Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial
Lancet Neurol
(2008) - et al.
Antihypertensive treatment and prevention of stroke and dementia
Semin Cerebrovasc Dis Stroke
(2003) - et al.
Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review
Am J Geriatr Pharmacother
(2009)
Relationship between blood pressure and Alzheimer's disease in Linxian County, China
Life Sci
Global burden of hypertension: analysis of worldwide data
Lancet
Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine
J Psychiatr Res
Memory impairment in patients with late-onset major depression: the effect of antidepressant therapy
J Affective Disord
Physical activity and Alzheimer's disease: from prevention to therapeutic perspectives
J Am Med Dir Assoc
Worldwide variability in physical inactivity a 51-country survey
Am J Prev Med
Immediate and delayed effects of cognitive interventions in healthy elderly: a review of current literature and future directions
Alzheimers Dement
Exercise builds brain health: key roles of growth factor cascades and inflammation
Trends Neurosci
Alzheimer's disease facts and figures
Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology
J Psychopharmacol
Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial
JAMA
Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial
JAMA
National Institutes of Health State-of-the-Science Conference statement: preventing Alzheimer disease and cognitive decline
Ann Internal Med
Actual causes of death in the United States, 2000
JAMA
Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia
Cochrane Database Syst Rev
The occurrence of lung cancer in man
Acta Unio Internationalis Contra Cancrum
A review of adjusted estimators of attributable risk
Stat Methods Med Res
Confounding and bias in the attributable fraction
Epidemiology
An illustration of and programs estimating attributable fractions in large scale surveys considering multiple risk factors
BMC Med Res Methodol
Comparison of adjusted attributable risk estimators
Stat Med
Risk of incident Alzheimer's disease in diabetic patients: a systematic review of prospective trials
J Alzheimers Dis
Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis
PLoS One
Effect of the treatment of type II diabetes mellitus on the development of cognitive impairment and dementia
Cochrane Database Syst Rev
Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: a systematic review
Vasc Health Risk Manag
Global prevalence of diabetes: estimates for the year 2000 and projections for 2030
Diabetes Care
Vital and health statistics: summary health statistics for US adults: National Health Interview Survey, 2009
Blood pressure and dementia—a comprehensive review
Ther Adv Neurol Disord
Cardiovascular risk factors and incident Alzheimer disease: a systematic review of the literature
Alzheimer Dis Assoc Disord
Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study
BMJ
Midlife pulse pressure and incidence of dementia: the Honolulu-Asia Aging Study
Stroke
Midlife cardiovascular risk factors and risk of dementia in late life
Neurology
Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study
J Am Geriatr Soc
Health: Unites States, 2010: with special feature on death and dying
International Data Base (IDB), 2010
Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis
Obes Rev
Measures of adiposity and dementia risk in elderly persons
Arch Neurol
Midlife and late-life obesity and the risk of dementia: cardiovascular health study
Arch Neurol
Predicting risk of dementia in older adults: the late-life dementia risk index
Neurology
Overweight and obesity in old age are not associated with greater dementia risk
J Am Geriatr Soc
Incident dementia in women is preceded by weight loss by at least a decade
Neurology
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