The aim of this meta-analysis is to evaluate the prevalence and incidence of AD in . and Stroke-Alzheimer's Disease and Related Disorders Association;. Keywords: aging, Alzheimer's disease, epidemiology, incidence, prevalence, .. The lifespan-dependent relationship between body mass index (BMI) and risk. Background Prevalence studies on dementia and Alzheimer disease (AD) have reported a positive association with age. However, the trend of the association in .
Here, we investigate whether differences in microbial diversity can explain patterns of age-adjusted AD rates between countries. We use regression models to test whether pathogen prevalence, as a proxy for microbial diversity, across countries can explain a significant amount of the variation in age-standardized AD disability-adjusted life-year DALY rates. We also review and assess the relationship between pathogen prevalence and AD rates in different world populations.
Based on our analyses, it appears that hygiene is positively associated with AD risk. Countries with greater degree of sanitation and lower degree of pathogen prevalence have higher age-adjusted AD DALY rates.
Variation in hygiene may partly explain global patterns in AD rates. Microorganism exposure may be inversely related to AD risk. These results may help predict AD burden in developing countries where microbial diversity is rapidly diminishing.
Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention
Epidemiological forecasting is important for preparing for future healthcare needs and research prioritization. The immunodysregulation of autoimmunity has been associated with insufficient microorganism exposure [ 1 ]. Global incidence patterns of autoimmune diseases reflect this aspect of their etiology: The similarity in immunobiology may lead to similarity in epidemiological patterns. For this reason, here we test the hypothesis that AD incidence may be positively correlated to hygiene.
The possibility that AD incidence is related to environmental sanitation was previously introduced by other authors [ 56 ], and remains as of yet untested. Low amount of microbe exposure leads to low lymphocyte turnover in the developing immune system, which can lead to immunodysregulation.
Epidemiological studies have found that populations exposed to higher levels of microbial diversity exhibit lower rates of autoimmunities as well as atopies [ 9 ], a pattern that holds for countries with differing degrees of development [ 1011 ].
Differences in environmental sanitation can partly explain the patterns of autoimmunity and atopy across history and across world regions [ 212 ]. Global aging The aging of populations has become a worldwide phenomenon [ 1 ].
Epidemiology of Alzheimer’s Disease
In26 nations had more than two million elderly citizens aged 65 years and older, and the projections indicate that an additional 34 countries will join the list by The largest increase in absolute numbers of old people will occur in developing countries; it will almost triple from million in to an estimated million in Developed countries, which have already shown a dramatic increase in people over 65 years of age will experience a progressive aging of the elderly population.
Decreasing fertility and lengthening life expectancy have together reshaped the age structure of the population in most regions of the planet by shifting relative weight from younger to older groups.
Both developed and developing countries will face the challenge of coping with a high frequency of chronic conditions, such as dementia, which is a characteristic of aging societies.
These conditions impair the ability of older persons to function optimally in the community and reduce well-being among affected individuals and their families. Further, these conditions are associated with significant health care costs that must be sustained by the society at large. Thus, the global trend in the phenomenon of population aging has a dramatic impact on public health, healthcare financing and delivery systems throughout the world [ 4 ]. Due to the aging of the population, dementia has become a major challenge to elderly care and public health.
The cognitive deficits include memory impairment and at least one of the other cognitive domains, such as aphasia, apraxia, agnosia or disturbances in executive functioning [ 56 ].
The disease frequently starts with memory impairment, but is invariably followed by a progressive global cognitive impairment [ 8 ]. Vascular dementia is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or haemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis of vascular dementia requires cognitive impairment; vascular brain lesions, often predominantly subcortical, as demonstrated by brain imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia [ 9 ].
The only exceptions are certain rare, inherited forms of the disease caused by known genetic mutations. This occurs because disruption of brain cell function usually begins in brain regions involved in forming new memories. As damage spreads, individuals experience other difficulties. Those in the final stages of the disease lose their ability to communicate, fail to recognize loved ones and become bed-bound and reliant on around-the-clock care.
The prevalence reflects the public health burden of the disease, whereas the incidence indicates the risk of developing that disease. Prevalence Based on the available epidemiological data, a group of experts estimated that The number of people affected will double every 20 years to Similar estimates have been reported previously [ 12 ].
Most people with dementia live in developing countries. China and its western Pacific neighbours have the highest number of people with dementia 6 millionfollowed by the European Union 5. Worldwide, the global prevalence of dementia was estimated to be 3. The number of people with dementia is anticipated to double every 20 years. Despite different inclusion criteria, several meta-analyses and nationwide surveys have yielded roughly similar age-specific prevalence of AD across regions Figure 1 [ 17 ].
Age-specific prevalence of Alzheimer's disease per population across continents and countries. Epidemiological research of dementia and AD in low- and middle-income countries has drawn much attention in recent years. Indeed, the prevalence rates of dementia in India and rural Latin America were approximately a quarter of the rates in European countries.
Similar prevalence rates of dementia were also reported from the urban populations of Latin American nations such as Havana in Cuba 6. Incidence The global annual incidence of dementia is around 7.
Slightly lower rates have been detected in the USA in comparison with Europe and Asia, and this is possibly due to differences in the study designs and the case ascertainment procedures. The Cache County Study further found that the incidence of AD increased with age, peaked, and then started to decline at extreme old ages for both men and women [ 29 ].
The apparent decline suggested in some studies may be an artifact of poor response rate and survival effect in these very old age groups. Age-specific incidence of Alzheimer's disease per 1 person years across continents and countries. The pooled data of eight European studies suggested a geographical dissociation across Europe, with higher incidence rates being found among the oldest-old people of north-western countries than among southern countries [ 26 ].
Differences in methodology e. The study using identical methods in UK found no evidence of variation in dementia incidence among five areas in England and Wales [ 30 ]. Studies have confirmed that AD incidence in developing countries is generally lower than in North America and Europe.
Prognosis and impact Dementia is one of the leading causes of death in older people. However, death certificates grossly underreport its cause, even when multiple underlying causes of death are taken into account. The community-based follow-up studies could provide reliable data on mortality. In the Swedish Kungsholmen Project of people aged 75 years or over, the mortality rate of dementia was 2. This progression is due to both cognitive and functional decline [ 33 ].
Dementia is strongly associated with disability as it has been found to be the major determinant of developing dependence and functional decline over three years. Approximately half of the persons who developed functional dependence in a three year period can attribute to dementia [ 34 ]. In industrialised countries, mental disease and cognitive impairment are the most prevalent disorders among older adults living in nursing homes or other institutions.
However, institutionalisation of demented patients varies depending on age structure, urban or rural residence, and other cultural aspects. Dementia triples the risk of death [ 35 ]. The demands of healthcare and social service of the huge and rapidly growing numbers of dementia patients have a major economic impact at the societal level [ 36 ]. The worldwide direct costs for dementia in were estimated at billion USD in the main scenario of a worldwide prevalence of It is obvious that due to these costs and the expected increase in the number of elderly people in developing countries, the dementing conditions will present a great challenge [ 3738 ].
Population-based prospective study is the major epidemiological approach to identifying influential factors for chronic multifactorial diseases such as dementia, in which the life-course approach should be taken into consideration. The majority of AD cases are sporadic, with considerable heterogeneity in their risk profiles and neuropathological features. Everyone inherits one form of the APOE gene from each parent.
Several other genes have been examined as possible candidates, but the reports are sporadic, and the results are inconsistent [ 42 ]. However, not all 4-carriers develop dementia. Female sex is often associated with an increased risk of AD, especially at the oldest-old age [ 25 ].
Men seem to be at greater risk for vascular dementia than women [ 51 ]. Blood pressure Several studies have consistently reported an association between midlife high blood pressure and increased risk of dementia and Alzheimer's disease [ 5253 ]. Hypertension has been linked to neurodegenerative markers in the brain, suggesting that long-term high blood pressure may play a causal role in the neurodegenerative process itself or by causing brain atrophy.
All these findings suggest that the relation of blood pressure to dementia may be age-dependent [ 25 ]. Recent follow-up studies have suggested that the protective effect of antihypertensive therapy on dementia and AD may depend on the duration of treatment and the age when people take the medications; the more evident efficacy was seen among young-old people i.
Evidence from clinical trials of antihypertensive therapy and dementia is summarized in the section on intervention trials towards primary prevention. Antihypertensive treatment may protect against dementia and AD by postponing atherosclerotic process, reducing the number of cerebrovascular lesions, and improving cerebral perfusion [ 52 ].
It has also been suggested that some antihypertensive agents e. The recent neuropathological study found substantially less Alzheimer neuropathological changes i. Cardiovascular disease A healthy heart helps ensure that enough blood is pumped through blood vessels to the brain. Other cardiovascular diseases, such as heart failure and atrial fibrillation, have been independently related to increased risk of dementia. Cerebrovascular disease Cerebrovascular changes such as haemorrhagic infarcts, small and large ischemic cortical infarcts, vasculo-pathie, and white matter changes all increase the risk of dementia [ 13 ].
Systematic reviews of population-based studies reveal an approximately two- to four-fold increased risk of incident dementia associated with clinical stroke post-stroke dementia. Multiple cerebral infarcts, recurrent and strategic strokes are main risk factors for post-stroke dementia.
Silent stroke and white matter lesions detected on neuroimaging are associated with increased risk of dementia and cognitive decline. Spontaneous cerebral emboli were related to both AD and VaD. Cerebral vascular lesions may interact with neurodegenerative lesions to produce a dementia syndrome in individuals not having sufficient neurodegenerative damages to express dementia [ 25 ].