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Understanding Alzheimer's Disease. The aging of populations has become a worldwide phenomenon [ 1 ].
In26 nations had more than two million elderly citizens aged 65 years and older, and the projections indicate that an additional 34 countries will the list by The largest increase in absolute s 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 ificant 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.
Dementia is defined as a clinical syndrome, and characterized by the development of multiple cognitive deficits that are severe enough to interfere with daily functioning, including social and professional functioning. 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 spre, individuals experience other difficulties.
Those in the final stages of the disease lose their Women 43129 who want sex to communicate, fail to recognize loved ones and become bed-bound and reliant on around-the-clock care. The occurrence of a disease can be measured as proportion of people affected by the disease in a defined population at a specific time point prevalenceor as of new cases that occur during a specific time period in a population at risk for developing that disease incidence.
The prevalence reflects the public health burden of the disease, whereas the incidence indicates the risk of developing that disease. Based on the available epidemiological data, a group of experts estimated that The of people affected will double every 20 years to Similar estimates have been reported ly [ 12 ].
Most people with dementia live in developing countries. China and its western Pacific neighbours have the highest of people with dementia 6 millionfollowed by the European Union 5. Worldwide, the global prevalence of dementia was estimated to be 3. The 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.
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 des 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 Women 43129 who want sex 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. 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. 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 s of dementia patients have a major economic impact at the societal level [ 36 ]. The worldwide direct costs for dementia in were estimated at billion Women 43129 who want sex in the main scenario of a worldwide prevalence of It is obvious that due to these costs and the expected increase in the 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 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 ]. 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 Women 43129 who want sex 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 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. 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 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 ]. Neuropathological studies suggested that cerebrovascular lesions, atherosclerosis, and neurodegenerative changes in the brain often coexist, and may be coincident processes converging to cause additive damage to the aging brain and to promote clinical expression of the dementia syndrome [ 61 ].
A potential link between diabetes and cognitive impairment was first reported more than 80 years ago. The association of diabetes with these cognitive changes is now well established [ 62 ]. There is substantial evidence suggesting that type 2 diabetes is associated with cognitive impairment involving both memory and executive function [ 63 - 65 ].
Several large longitudinal population-based studies have also shown that the rate of cognitive decline is accelerated in elderly people with type 2 diabetes [ 66 ]. An increased risk of not only vascular dementia but also neurodegenerative type dementia among persons with diabetes has been reported in several longitudinal studies [ 67 - 70 ], and the risk effect was confirmed by a systematic review [ 71 ]. Similar to hypertension, recent studies suggested a lifespan-dependent relation of obesity with dementia [ 7576 ].
A higher body mass index BMI at middle age was related to an increased risk of dementia in late life [ 7778 ]. Controversial findings have also been reported on the relation of cholesterol in late life to dementia risk. Some cohort studies found no association or even an inverse association of total cholesterol with dementia risk [ 84 ].
A study showed a decline in total cholesterol at least 15 years before dementia onset [ 85 ]. Recently, a bidirectional cholesterol-cognition relationship has been reported. High midlife cholesterol was associated with poorer late-life cognition, but decreasing cholesterol after midlife may reflect poorer cognitive status [ 86 ].
A clustering of interrelated metabolic risk factors such as diabetes, obesity, hypertension and dyslipidaemia has received increasing attention in the past few years. Several components of the metabolic syndrome have been individually related to cognitive outcomes. A prospective study found that the metabolic syndrome contributed to cognitive decline [ 87 ]. But this finding was not confirmed in a population of the oldest old. The concept of the metabolic syndrome may be less valid in this age group [ 88 ].
Excessive alcohol intake can cause alcoholic dementia and may increase the risk of vascular dementia. Heavier alcohol intake Women 43129 who want sex middle age was associated with increased risk of late-life dementia [ 91 ]. By contrast, increasing evidence suggests that light to moderate alcohol consumption may be associated with a reduced risk of dementia and cognitive decline [ 92 ], a similar effect as observed for cardiovascular disease [ 25 ].
However, the role of moderate alcohol consumption in dementia still remains controversial because the inverse association may be due to information bias, the confounding of healthy lifestyles and high socioeconomic status, different approaches in assessments of alcohol consumption, or outcome misclassification. The relationship between smoking and cognitive decline remains uncertain. Diets high in fish, fruits and vegetables are high in Women 43129 who want sex and polyunsaturated fatty acids PUFAs.
Investigations on the effect of dietary PUFAs on the risk of cognitive dysfunction proved inconclusive. Fatty acids may affect dementia through various mechanisms such as atherosclerosis and inflammation. Psychological factors include social economic status, education attainment in early life, and work complexity in adult-life and leisure activities. Evidence from epidemiological research has been accumulating that some psychosocial factors and healthy lifestyle may postpone the onset of dementia, possibly by enhancing cognitive reserve. In most of these studies, SES was assessed based on occupational attainment, current income to reflect socioeconomic level in adulthood, or educational attainment.
Low dementia prevalence among highly educated persons has been reported by numerous surveys.
Educational attainment and lifespan mental activity associated with childhood education may reduce the risk of dementia [ 25 ]. The cogntive reserve hypothesis has been proposed to interpret this association such that education could enhance neural and cognitive reserve that may provide compensatory mechanisms to cope with degenerative pathological changes in the brain, and therefore delay onset of the dementia syndrome [ 17 ].
Alternatively, educational achievement may be a surrogate or an indicator of intelligent quotient, early life living environments, and occupational toxic exposure experienced over adulthood [ ]. Basic science and observational evidence on humans strongly supports the hypothesis that increased physical activity prevents the onset of dementia.
Regular exercise, even low-intensity activity such as walking, has been associated with reduced risk of dementia and cognitive decline . In the Kungsholmen Project, the component of physical activity presenting in various leisure activities, rather than sports and any specific physical exercise, was related to a decreased dementia risk [ ].
As it may take years to achieve high levels of physical fitness, brief periods of exercise training may not have substantial benefits on cognitive processes, but could still be detectable in the subsets of cognitive domains that are more sensitive to the age related decrements. Physical activity is important not only in promoting general and vascular health, but also in promoting brain plasticity, and it may also affect several gene transcripts and neurotropic factors that are relevant for the maintenance of cognitive functions.
There is now increasing amounts of trial evidence to support this hypothesis in terms of cognitive benefits in healthy older adults as well as in people at risk for dementia. However, to date there are no RCTs confirm that increased physical activity prevents dementia. Various types of mentally demanding activities have been examined in relation to dementia and AD, including knitting, gardening, dancing, playing board games and musical instruments, reading, social and cultural activities, and watching specific television programs, which often showed a protective effect [ ].
The Canadian Study of Health and Aging found that high complexity of work appeared to be associated with a reduced risk of dementia, but mostly for vascular dementia [ ]. In supporting of these findings, the recent neuroimaging study suggested that a high level of complex mental activity across the lifespan was Women 43129 who want sex with a reduced rate of hippocampal atrophy [ ]. A poor social network or social disengagement in late life was associated with an elevated risk of dementia.
Evidence from longitudinal observational studies suggests that a poor social network or social disengagement is associated with cognitive decline and dementia . The risk for dementia and AD was also increased in older people with increasing social isolation and less frequent and unsatisfactory contacts with relatives and friends. Furthermore, low social engagement in late life and a decline in social engagement from middle age to late life were associated with a doubly increased risk of developing dementia and AD in late life.
Rich social networks Women 43129 who want sex high social engagement imply better social support, leading to better access to resources and material goods [ ].Women 43129 who want sex
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