In 2017, a Review article titled Recent Progress in Alzheimer’s Disease Research was published in the Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 317-330, 2017. The authors (Robinson, Morgan, Lee, Brenda Y., and Hane, Francis T.) draw the attention to the fact that "Epidemiological and genetic studies are revealing important insights into the etiology of, and factors that contribute to Alzheimer’s Disease (AD), as well as areas of priority for research into mechanisms and interventions. The widespread adoption of genome wide association studies has provided compelling evidence of the genetic complexity of AD with genes associated with such diverse physiological function as immunity and lipid metabolism being implicated in AD pathogenesis".
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EPIDEMIOLOGY
The pathogenesis of AD is multi-faceted and is not limited to one set of simple molecular interactions that occur with age in individuals with genetic predispositions to the disease itself. In the past decade or so, large strides have been made towards a better understanding of the epidemiology of AD, including its occurrence, risk factors, and methods of possible intervention.
Prevalence and incidence
The Center for Disease Control has estimated that the number of people over the age of 65 will increase from 420 million to almost 1 billion from 2000 to 2030. [...] Currently, there are over 36.5 million people in the world who are affected by dementia, and the majority of these cases are AD-related. Each year, an estimated 5–7 million new cases of AD are recorded in the geriatric population.
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The incidence of AD increases approximately exponentially with age until an inflection point is reached at the age of 85.
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Burden and impact
Since AD is an incurable progressive disease, persistent care and therapy can triple the expenditure of a typical AD patient compared to one without AD. Preventive strategies that can help delay the onset of AD will significantly help in reducing the global economic burden and societal impact of this disease, and closely monitoring AD risk factors may play a large role in these mitigating strategies.
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Factors affecting AD onset
Although old age is the primary risk factor for AD, there are many other risk and protective factors that may affect the progression or development of AD. These factors can be grouped into two main domains: pre-existing conditions or diseases and lifestyle choices.
Obesity is widely associated with an increased risk of hypertension, stroke, and diabetes. These diseases may be factors that increase the risk of cognitive decline, thereby playing an indirect role in the development of AD.
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Type 2 diabetes mellitus (T2DM) is associated with obesity and is often preceded by insulin resistance, followed by improper production of insulin resulting in an insulin deficiency, and therefore a decreased capability to metabolize glucose. T2DM has been shown to increase AD risk and neurodegeneration.
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Physical activity and diet are important in maintaining general overall health. Regular exercise has been reported to be associated with delayed AD onset and a reduced risk of dementia. [...] Daily physical activity has been correlated with a reduced cognitive decline and AD risk. Diet has also been shown have effects on cognition in elderly adults and AD. In particular, the Mediterranean diet and diets high in seafood have received a large amount of attention for being protective, while evidence suggests that diets high in sugar and saturated fats have detrimental effects on cognition.
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Mentally demanding activities may act as a protective factor against the onset and progression of AD [...] the cognitive reserve hypothesis ... posits that excess dendritic connections provide a reserve so that executive function is still retained with increasing cerebral atrophy.
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Stress is a factor in the development of many chronic conditions including AD, and levels of glucocorticoids are often correlated with cognitive deficits and AD pathology. The relationship between stress and the immune system may play an important role in explaining the link between stress and AD. Whether stress contributes to AD pathology or is a result of AD is not entirely clear; it is possible though, that AD pathology and stress act in a positive feedback loop, both exacerbating the other. Psychological well-being is important for healthy aging. Poor psychological well-being, as measured by self-reported vigor and activity, has been associated with greater AD pathology in subjects with mild cognitive impairment, compared to controls, as measured using PET imaging. Similar results have been reported in association with a sense of purpose in life, where postmortem analysis of 246 older adults revealed higher levels of purpose reduced AD pathology and cognition.
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CONCLUSION
Key themes have emerged in both genetic and epidemiological studies in AD that may continue to support a central pathology surrounding amyloidosis via Aβ production (from AβPP processing) and accumulation (from impaired metabolism and clearance). The Aβ pathway is than further influenced by other genetic and epidemiological risk factors that have been identified and described in this review including tau neurotoxicity, lipid/protein homeostasis, innate immunity, and lifestyle choices. As lipid homeostasis (trafficking and metabolism) plays a critical role in innate immunity via lipid mediators and changes in cell membrane composition it should not be surprising to see these common themes emerge, especially considering the pathology of AD contains microglial activation and features of neuroinflammation. The observations reported in this review could alternatively support a hypothesis of AD where immunological dysfunction (including dysfunction as a result of impaired lipid trafficking and metabolism) is the primary insult that results in the overproduction and accumulation of Aβ the associated pathology along with hyperphosphorylated tau and oxidative stress inparallel.
Epidemiological studies have demonstrated that healthy active lifestyles with moderate exercise and carefully maintained mental health, may serve to delay the onset of late onset AD (LOAD). Meanwhile, genetic studies have identified novel targets for the development of pharmaceuticals which modulate the influence of low risk genetic factors.
Robinson, Morgan, Lee, Brenda Y., and Hane, Francis T. ‘Recent Progress in Alzheimer’s Disease Research, Part 2: Genetics and Epidemiology’. 1 Jan. 2017 : 317 – 330.
Reference:
Robinson, Morgan, Lee, Brenda Y., and Hane, Francis T. ‘Recent Progress in Alzheimer’s Disease Research, Part 2: Genetics and Epidemiology’. 1 Jan. 2017 : 317 – 330.
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