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 Table of Contents  
SPECIAL ARTICLE
Year : 2014  |  Volume : 2  |  Issue : 1  |  Page : 87-95

Targeting brain-health from "cradle to grave": Can we prevent or delay dementia?


Department of Neurology, Yenepoya Medical College, Yenepoya University, Mangalore, Karnataka, India

Date of Web Publication4-Jun-2014

Correspondence Address:
Bhaskara P. Shelley
Department of Neurology, Yenepoya Medical College, Yenepoya University, Mangalore - 575 018, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2321-4848.133846

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  Abstract 

Dementia or the "silver tsunami" is a public health challenge of epidemic proportions of the 21 st century. It imposes enormous burden in terms of economic and social impact on the health care systems and the quality of life of people with dementia, their families and caregivers. For a number of decades, clinicians, researchers, and pharmaceutical companies have laid emphasis on the development of a drug armamentarium for fighting dementia. However, the neurotherapy of dementia targeting the "pathogenesis model" still remains disappointing with no breakthrough in-sight. The cure for dementia is worthy, but an elusive and frustrating goal. On the contrary, epidemiological research does spell optimism and provides a substantial amount of evidence of modifiable risk and protective factors to delay, prevent or shorten dementia. Thus time has come for a "strategic vision for the future" to move away from the current paradigm of curative therapies to a strategy of "preemptive medicine" that identifies disease processes at the earliest stages and prevents rather than attempting to reverse disability. Such a strategy is not only a safer, more dignified option, but also a step forward for a sustainable society in an aging world in order to preserve the mental capital and brain well-being of nations. This would reiterate the concept of "anthroposophical medicine," neurocentric health and preventive neurology strategies to promote healthy brain aging and brain protection. The need to rethink and redefine dementia from a "salutogenesis" perspective as a "lifestyle disorder" and implement multiple preventative life-course approaches through well-designed randomized controlled trials is quintessential to delay, prevent or keep dementia at bay.

Keywords: Dementia, prevention, pathogenesis, salutogenesis, risk factors, brain-healthy lifestyle, epidemiology, aging, healthy brain aging, randomized controlled trials


How to cite this article:
Shelley BP. Targeting brain-health from "cradle to grave": Can we prevent or delay dementia?. Arch Med Health Sci 2014;2:87-95

How to cite this URL:
Shelley BP. Targeting brain-health from "cradle to grave": Can we prevent or delay dementia?. Arch Med Health Sci [serial online] 2014 [cited 2019 Dec 9];2:87-95. Available from: http://www.amhsjournal.org/text.asp?2014/2/1/87/133846


  Introduction Top


The World Alzheimer Report estimated the number of people with dementia worldwide as 35.6 million in 2010 and this is extrapolated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced. [1] India occupies the 2 nd largest elderly population in the world reflecting an aging nation. India is a home to 70 million people older than 60 years as per the 2001 census. Dementia has become a growing public health challenge of the 21 st century due to the enormous burden these disorders impose on health care systems. [2] In 2010, there were 3.7 million Indians with dementia and this figure is expected to double by 2030. [3]

The two most common types of dementia, an "epidemic of our century," are Alzheimer's disease (AD) and vascular dementia (VaD). AD accounts for 50-70% of all cases of dementia, about 20-30% have either VaD or a combination of VaD and AD. It is very unlikely that in the near future, a new efficacious treatment for AD, VaD, and mixed dementia would become available. And even if that would happen in the near future, it is unrealistic to expect such a treatment to become widely available for the majority of people in developing countries.

Epidemics can only be eradicated by prevention, not by therapy. The cornerstone for our current best hope for dementia prevention [4],[5],[6],[7],[8] through healthy brain aging (HBA) strategies [9] stems from the fact that the neuropathologic hallmarks of AD begins in early to mid-life. [10] However, our current armamentarium against dementia is fundamentally based on the "pathogenesis model." This model is based on amyloid synaptotoxicity, tau hyperphosphorylation related neurotoxicity and neurodegeneration. [11],[12],[13] This model is similar to the idiom "closing the stable door after the horse has bolted." Current treatment into AD is "too late" and we need to look backward to earlier stages of cognitive impairment on a moving background of aging such as brain at risk, asymptomatic AD (ASYMAD), subjective cognitive impairment (SCI) or pre-mild cognitive impairment (pre-MCI), MCI, mild behavioral impairment (MBI), and early AD. In order to delay, prevent or shorten the course of dementia, promotion and preservation brain well-being from the "cradle to grave0" as a life-course perspective [14] incorporating the "salutogenesis model" would provide longer lasting solutions to this pandemic of dementia. The " pathogenesis/dis-ease" model is centered on fighting and combating illness, whereas the " salutogenesis/health-ease" model has the core essence of promoting health [15] by shifts in thinking from the "pathogenesis/dis-ease" model to a "salutogenesis/health-ease" model is quintessential.

Human work force, globalization and socioeconomic endeavors in this planet ultimately depend on the "mental wealth" or "mental capital" of our citizens. [16] Nations should protect and capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. It is absolutely essential to realize that "mental wealth" can only be attainable by preservation of brain function, promoting brain-health, cognitive and emotional health, promoting cognitive resilience, and cognitive reserve, all of which stress the salutogenic approaches to neurocentric health. An urgent call for building bridges uniting the "pathogenesis-salutogenesis" dichotomy of human brain disorders like dementia and severe cognitive impairment would certainly pave the way for a holistic meta-medicine system of health care for successful/HBA and preserving citizens mental health capital rather than curative obsessions.


  Shifts in Thinking About Dementia Top


The neurobiological substrates for dementia such as amyloid plaques and neurofibrillary tangle actually start 20-30 years earlier during early to mid-life. AD is thus a slow cumulative neurodegenerative and neuropathological decades-long process. As neuronal degeneration and the formation of neurofibrillary tangles and neuritic plaques gradually progress, a threshold for the initiation of clinical symptoms of the dementia syndrome is eventually reached. By the time patients begin to suffer from the symptoms of dementia, AD has already caused significant and irreversible damage. Research on AD has undergone a paradigm shift from viewing it as a disease of old age to taking a life-course perspective. Several vascular, lifestyle, psychological and genetic risk factors influencing this latent period have been recognized and they may act both independently and by potentiating each other. [17] For the 1 st time in 30 years, clinical diagnostic criteria for AD have been revised in 2011. [18] They proposed a staging framework for an expanded recognition (asymptomatic preclinical cerebral amyloidosis phase; symptomatic predementia phase-MCI; and the dementia phase) to try to better define individuals at the greatest risk for developing clinical cognitive impairment, prevent early pathology from causing the catastrophic symptoms of full-blown disease, and to allow early detection of these stages.

Another shift in thinking about AD is that AD and VaD rarely occur in isolation. Both types of dementia share many risk factors and pathologic features with atherosclerosis. In addition, the presence and severity of cerebrovascular pathologic findings appear to increase the risk and stage of AD for any given level of AD neuropathologic findings. Thus, clinical dementia is a mixture of neurodegnerative and vascular features which may be impossible to disentangle. Dementia therefore is a spectrum disorder, a continuum of cognitive impairment, with a common coexistence of vascular risk factors (VRFs) and probable interaction of cerebrovascular disease, VaD and AD on the moving background of aging. [19],[20],[21]


  Concept of Preventive Neurology, Brain Well-being and Brain-healthy Lifestyle Top

" You do not heal old age, you protect it, you promote it, you extend it" by Sir James Sterling Ross and " it is not what life takes away from you that count. It's what you make of what is left with you" by Hubert Humphert epitomizes the salutogenic theory of positive brain-health promotion. Achieving good health for all means not just reacting to ill-health!

Mental and neurological disorders constitute more than 34% of the global burden of disease, and this will certainly reduce the "mental health capital" or "mental wealth" of all nations. [18] The coming decade may well become the "decade of brain fitness," as neuroscientists, and clinicians test the limits of current knowledge and research for improving and sustaining human cognitive and emotional health to the end of life.

Given that the current drug treatment of dementia can only modestly improve symptoms and lack evidence of a disease-modifying effect, preventive neurology [22] and HBA would be the cornerstone to reduce the prevalence and global burden of dementia epidemic. The prevalence of dementia would be reduced by 50% if risk reduction strategies were successful in delaying its onset by 5 years. The collective wisdom that spells optimism for preventive neurology and HBA strategies to be the goal for the future to prevent, delay or ameliorate the course of dementia stem from a few longitudinal population based studies, large observational studies, randomized controlled trials (RCTs), and research data from centenarian and super centenarian models of successful brain aging.

Healthy brain aging has its foundation on the " Salutogeneis Model of Health" that was proposed by Aaron Antonovsky an American-Israeli medical sociologist in 1979. [15] According to this salutogenic perspective, each person should engage in health promoting actions (" the wheel of wellness") to cause health while they secondarily benefit from the prevention of disease and infirmity. Considering the epidemic proportion of dementia, the time has come for a change in emphasis from treating ill-health to promoting good health in order to create, enhance, and improve physical, cognitive, emotional, and social well-being. Brain-health not only encompasses mental health but should address cognitive, emotional and spiritual health too. Cognitive health as it pertains to the elderly should be defined "not just as the absence of disease, but rather as the development and preservation of the multidimensional cognitive structure that allows the elderly to maintain social connectedness, an ongoing sense of purpose, and the abilities to function independently, to permit functional recovery from illness or injury, and to cope with residual functional deficits." Like cognitive health, emotional health is not simply the absence of psychiatric illness, but the presence of positive emotional adaptation in areas such as emotional regulation (the ability to control one's emotions) and emotional intelligence (the ability to use and identify emotions constructively). Emotional health comprises personal traits that promote successful adaptation, such as resilience, mastery, self-efficacy, and wisdom. Self-efficacy and the ability to engage with others may ward off the sadness and depression that often characterize old age and speed cognitive decline.

Healthy brain aging is a burgeoning field that proposes a link between brain-health behaviors (brain-healthy lifestyle) and maintenance of brain-health. In this context, dementia should be recognized as a lifestyle disease. HBA include lifestyle risk factor and behavioral risk factor intervention strategies. Most people are bothered about organ-specific health, and so even total body health is not a deep or broad concept to encompass "brain-health' for the future." Healthy brain program thus takes brain-health to a deeper and broader level and it may not be long before " healthy brain lifestyle 2020" as a public health strategy becomes a reality for all.

Is dementia a curse that is inescapably linked to old age? Dementia is a disorder on the "continuum of aging casualty" and therefore aging is not necessarily accompanied by typical age-associated declines in function. To move away from a pessimistic view of old age, I would like to refer the readers to three studies:

  1. Nun study, [23],[24]
  2. The Okinawa Centenarian Study (OCS), [25] and
  3. Kimberley indigenous Australian study. [26]



  'Life at the Extreme Limit'-Models of Healthy Brain Aging Top


Dementia is not inevitable with aging. These studies cited above clearly shows optimism of centenarian and super centenarian models of healthy, successful, positive and creative brain aging.

The Nun study is a longitudinal study of aging funded by the National Institute on Aging involving the Teaching sisters of Notre Dame (USA); 678 sisters were enrolled since 1991 (age 75-102); archived written autobiographies (data on early life positive emotions; idea density; linguistic skills studied); underwent annual cognitive testing; and by 2003 autopsies were done for 400 deceased sisters. The findings from this study revealed that traits in early, mid, and late-life have strong relationships with the risk of AD, as well as the mental and cognitive disabilities of old age. The degree of resistance to the clinical manifestation of AD despite having abundant neuropathology burden and even ApoE genetic predisposition reflects augmented cognitive reserve. The cognitive reserve, neuroplasticity and brain resilience is linked to life-course events, social factors, nutrition, intellectual stimulation, education, and lifelong learning that strongly lend evidence for the salutogenesis model, concept of brain protection and brain well-being. [23]

Elderly Okinawans in Japan has been documented to have the lowest mortality rates in the world from a multitude of chronic geriatric diseases and as a result enjoy not only what may be the world's longest life expectancy, but the world's longest health expectancy. A "new generation" of centenarians has arisen in Japan, and the total population of persons 100 years old or older reached 32,295 with a centenarian prevalence rate of 25.28 centenarians per 100,000 in 2007. The OCS investigated the genetic and lifestyle factors responsible for this remarkable successful aging phenomenon for the betterment of the health and lives of all people. This elite group of " dementia free centenarians," supernormal centenarians, super centenarians is longevity champions who could unlock the mysteries of health or successful aging. The traditional Okinawans had healthier lifestyles, consumed a low calorie diet, low glycemic load diet, low body mass index (18-22), and had low blood levels of free radicals, low cholesterols, and low homocysteine all of which reduced aging-related free radical damage, lowered incidence of coronary heart disease and stroke, low cancer and osteoporosis. Their healthy lifestyle included healthy diet comprising of low caloric intake, high vegetables/fruits consumption, higher intake of good fats (omega-3, mono-unsaturated fat), high fiber diet, high flavonoid intake; regular exercise; avoidance of smoking; blood pressure control; and a stress-minimizing psycho spiritual engagement. These exceptional survivors do seem to be more resilient or better able to delay or adapt to major chronic disease, and thus maintain biological function significantly longer. [27]

The Kimberely indigenous aboriginal population of Australia has been recently studied for the prevalence of dementia and cognitive impairment. The study revealed that the life expectancy in this population was 17 years lower than the nonindigenous Australians, with a dementia prevalence of 12.5% compared to the Australian dementia prevalence of only 2.4%. This discrepancy was attributed to poorer health outcomes, higher cardiovascular disease, higher hypertension, diabetes mellitus, smoking, obesity, physical inactivity and poor quality diet (limited fruit/vegetable intake). [26]

Another study documented the relationship between parental longevity, cognitive aging and dementia. Data from the Bronx Aging Study did demonstrate that offspring of parents with exceptional longevity (OPEL) to have a lower rate of dementia than offspring of parents with usual survival suggesting that parental longevity protects against memory decline and the onset of dementia. [28] OPEL have been reported to have lower risk of cardiovascular disease, hypertension, diabetes mellitus, and dyslipidemia. These cardiovascular factors are also risk factors for dementia and AD. Thus their lower prevalence in OPEL could contribute to the lower rate of AD and memory decline. It is important to note that human longevity is a complex phenotype with multiple determinants with genetic and nongenetic factors. Genetic factors include "longevity genes" such as SIRT1 and FOXO which has a role in the insulin/insulin-like growth factor-1 -1 (IIS) signaling pathway. [29]


  Healthy Brain Aging Strategies; Taking Brain-Health to a Deeper and Broader Level Top


Over the last two decades of research (observational and longitudinal studies), there is moderately strong evidence to indicate that lifestyle, behavioral factors (LSRFs and BRFs), multiple VRFs, and cerebrovascular disease (CVD) are major factors in the pathogenesis of dementia, particularly AD and VaD, that contributes to a lion's share of total dementias. Adopting a healthy lifestyle from young can therefore slow down the onset of dementia in old age. The evidence that LSRFs/BRFs and VRFs are connected to ischemic heart disease and stroke is strong. Therefore, targeting these risk factors for the prevention of dementia is also appropriate. LSRFs and BRFs include physical exercise, cognitive activity, social and creative engagement, [30] leisure activities; diet, [31] cigarette smoking, alcohol, head trauma, depression, and associated lifetime chronic stressors. The VRFs include mid-life hypertension, diabetes mellitus, mid-life obesity, metabolic syndrome, hyperhomocysteinemia. The control of VRFs has also been shown to beneficially modify the influence of ApoE4. [32] In this context, the public health slogan should resonate with the caption " heart smart is brain smart."

The HBA strategies are targeted towards preserving brain function, increasing cognitive reserve, promoting brain resilience and preventing dementias. Such strategies should be translated to clinical care, public education as a tool for effective cognitive health messages, future dementia prevention research, and public policy. A healthy brain lifestyle/brain-health diet mandates the following:

  1. Stay mentally active by staying curious and involved and committing to lifelong learning: Read, write, work puzzles, attend plays or lectures, play games, garden, or pursue memory exercises;
  2. Remain socially active: Engage in social and leisure activities by volunteering, travelling, or joining social clubs;
  3. Stay physically active: Engage in activities such as walking, bicycling, gardening, yoga, and other physical activities for about 30 min daily;
  4. Avoid head injuries;
  5. Adopt a brain-healthy diet: Include antioxidant-rich foods and consider taking vitamin supplements; and
  6. Keep body weight, blood pressure, cholesterol, and blood sugar under control.


Cardiovascular risk factors have been associated with an increased risk for the development of an unhealthy brain in later-life. [33] Therefore multi-component "intensive vascular care" during mid-life would be a window of opportunity to increase the level of "HBA" and prevent, delay or shorten the course of late-life dementia. [34] A recent study in 2009 clearly showed that aggressive treatment of all VRFs in patients who have established AD was associated with a slower cognitive decline. They suggested that dementia should not prevent treatment of multiple VRFs. [35]

Increasing evidence points to the potential risk roles of vascular factors and disorders (e.g., mid-life obesity, dyslipidemia, diabetes, high blood pressure, cigarette smoking, and cerebrovascular lesions) and the potential protective roles of psychosocial factors (e.g., higher education, regular exercise, healthy diet, intellectually challenging leisure activities, and active socially integrated lifestyle) in the pathogenic process and clinical manifestation of dementing disorders. [5] Since dementia is now viewed as a "lifestyle disease," the simple and inexpensive solutions for dementia would be to recognize the connection between brain-health attitudes and cognitive health such as physical exercises, cognitively stimulating activities, social activities and other creative engagements. Higher level of education and life-long learning appears to reduce the risk for dementia. More frequent participation in cognitive activity is associated with reduced incidence of dementia. [36] A cognitively inactive person seems to be more likely to develop AD than a cognitively active person. Frequent cognitive activity across the life span has an association with slower late-life cognitive decline that is independent of common neuropathologic conditions; consistent with the cognitive reserve hypothesis. [37] There even appears to be a dose-response relationship of education, each additional year of formal education further delays the time of accelerated cognitive decline.

The brain is a social organ and therefore creative engagement (e.g., storytelling, painting, song writing, dance, yoga, spirituality, and drama) strengthens resilience. Socially integrated lifestyle with rich social networking, leisure activities, mentally stimulating activities (reading, playing musical instruments, doing crossword puzzles or Sudoku, playing memory games, learning to play musical instruments, learning a foreign language, debates, visiting friends or relatives, going to movies or restaurants), and physical activity has demonstrated neuroprotective effects and retention of cognitive capacity or cognitive reserve. Psychosocial factors include a lack of social activity or social support networks, living alone, crystallized intelligence, and depressive episodes. Depression can be associated with significant cognitive deficits and can be co-morbid with dementia. Meta-analyses concluded that a history of depression may confer an increased risk for later developing AD and may act as an independent risk factor for the disease. [38],[39] Depression, chronic distress and life-long stressors (allostatic load) is associated with elevated cortisol levels, which may directly damage the hippocampus and increase the risk of dementia. Furthermore, recent studies have suggested that people with depression have enhanced deposition of β-amyloid plaques. [40],[41]

Yoga, Ayurveda and its Medhya rasayanas, Meditation and Pranayama are "push-ups for the brain" and paths to brain wellness. The neuroscience of meditation does indeed show structural changes in cortical thickness, grey matter density, gray and white matter neuroplasticity, changes in functional connectivity and anatomical connectivity, and changes in electroencephalography patterns. Moreover, the neural mechanisms of mindfulness-based stress reduction did also reveal an increase in gray matter concentrations in areas that were involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking. [42]

The literature from both animal and human trials on the science of dietary and caloric restriction (CR) and alternate-day fasting does show beneficial effects of fasting by promoting brain-health, HBA and life span through resistance of neurons to neurodegeneration, and chronic disease prevention such as type 2 diabetes mellitus, cardiovascular disease (CVD), and cancer. [43] Observational studies on the Okinawa centenarians revealed that the adult energy intake was 20% less than the Japanese national average. It is interesting to know that the anti-aging effects of CR is mediated at various levels, that is, through effective modulation of metabolic, mitochondrial bioenergetics, and functional risk factors, retardation of oxidative stress, improving insulin sensitivity, regulation of neuroendocrine status, suppression of apoptosis, and regulation of gene expression and preventing macromolecular damage. Nutrigenomics and nutrigenetics have also established an association between telomere length, telomerase activity, sirtuin activators, Mediterranean diet, and healthy aging. The so-called "MediterrAsian" diet that is especially rich in "sirtfoods" and CR exerts their effects through sirtuin activation. [44] Thus such dietary modifications may be promising new strategies in brain well-being to ensure protection against and recovery from the various aging-related neurological diseases, and steer human longevity towards successful and HBA. Future research studies in CR research are sorely needed, which could translate into new strategies for effective brain-healthy lifestyle interventions.

Brain-healthy diet such as consuming a Mediterranean diet, people with high consumption of fish, and having higher fruit and vegetable intake may have a lower risk of developing dementia and cognitive decline. Population studies have reported that intake of antioxidants (vitamin E and flavonoids) or polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid in fatty fish), B group vitamins such as folate, B6 and B12 and vitamin D to be associated with a reduced incidence of dementia.

According to the researchers in the field of exercise neuroscience, the volume of gray matter shrinks in late adulthood and often precedes cognitive impairment. Levels of physical activity in mid-life have also been linked to the development of AD in later-life. [45] In a study in 2010 researchers concluded that walking maintains brain volume, and prevents cognitive impairment. [46] They reported that at the 9 years point, participants who had reported walking at least about 6-9 miles a week at the start of the study, had more grey matter volume than those who walked less participation in physical activity and exercise has been hypothesized to protect against the deterioration of brain tissue. The results of this study suggested an association between physical activity, in the form of walking, brain structure, and dementia across the period of a decade. This certainly does provide yet another reason for the medical community to prescribe physical activity as means to reduce the probability of age-associated neurodegenerative disease. Exercise facilitates neuroplasticity in the brain as evidenced by enhanced brain neurotrophic factors, improved synaptogenesis, enhanced hippocampal functioning, modify apoptosis, and increased vascular reserve of the brain. [47],[48] Furthermore a recent study from a geriatric psychiatry outpatient clinic of a Brazilian public medical school did document that the regular practice of physical activity did not only contribute to a reduction in neuropsychiatric symptoms in dementia patients, but also to attenuate the burden of the caregivers of these patients with dementia. [49]


  Dementia Risk Predictive Scores Top


From a clinical and public health perspective, it is important to be able to predict who is at highest-risk of developing future dementia and when. Taking the cumulative and combined exposure to various potential modifiable behavioral and lifestyle risk factors and protective factors for the development of dementia, the development of a meaningful dementia risk index (DRI) would be crucial to identify and educate at-risk patients and family members of those with dementia about the relevance of addressing modifiable risk factors as early as possible so as to potentially delay or mitigate the expression of clinical dementia phenotype before death. [50] The two well known DRI include Cardiovascular risk factors Aging and Dementia (CAIDE) risk score [51] and the late-life DRI. [52]

Similar to the Framingham heart scores, such dementia predictor indices would form the fundamental basis for preventive neurology strategies. From a clinical and public health perspective, such risk assessments tools could be used in understanding who the target population is and when to start HBA interventions in such high-risk groups. Since dementia is now conceptualized on the "continuum of aging casualty," with a spectrum of asymptomatic preclinical stages, predementia stages to clinically overt mild, moderate and severe dementia, implementation of early to mid-life brain-healthy lifestyles targeted at as a prevention strategy spells optimism.

A recent study documented that the Framingham vascular risk scores for cardiovascular disease and stroke were more effective to predict cognitive decline in late middle age when compared with CAIDE risk score augmenting the established link between vascular health and cognition. [53]


  The Future Challenges: Neurocentric Health and Brain Well-being Top


With the dawn of the neurocentric age, HBA and preventive neurology strategies as a life-course approach model, from " conception/cradle to grave" must be advocated as the public health roadmap to maintaining cognitive health.

The negativistic attitude to preventive neurology and HBA strategies arose after the release of the National Institutes of Health (NIH) report that concluded that current research evidence on many risk and protective factors for cognitive decline and AD were not of sufficient strength, thus suggesting that the recommendations for prevention of dementia cannot be made. [54] However, it is crucial to note that these negative perspectives have been criticized since the analytical strategy used in the evidence-based review did not take into account the life-course perspective.

Is the glass half empty or full in the search for a safe, effective, and hopefully, affordable ways to prevent or delay dementia? It is important not to be dismayed by the report of the US Department of Health and Human Services NIH consensus conference on "Preventing Alzheimer's Disease and Cognitive Decline", instead to re-focus on multiple interventions targeting VRFs, and modifiable behavioral and lifestyle risk factors, and take up the challenges and methodological issues in designing dementia prevention trials in the future. [55] Thus, only properly designed RCTs of sufficient power and long follow-up can convincingly define the window of opportunity for prevention of dementia since dementia is a disorder resulting from cumulative brain damage with a long latent period. [56],[57]

Is it justifiable to seek to shape the environment and society to push or nudge people to adopt healthier lifestyles? I would reiterate that the absence of evidence is not the evidence for absence and should not be a boondoggle. Evidence should need to be translated, whether or not it is complete! For example, no RCT has ever evaluated whether smoking increases the risk for lung cancer, and therefore over-reliance on RCTs is similar to balancing the whole health care evidence on a one-legged stool. Although current research evidence is equivocal and limited on preventive neurology strategies that can delay or decline the onset of dementia, the promising data from large scale observational studies, certainly opens up the possibility that people who are able to take control of their lives can reduce their individual risk of dementia. As a public health road map to preventing or delaying dementia, all health care providers should educate patients and lay public about potential brain-health promoting effects of healthy lifestyle. Dementia education in children, school professionals, teenagers, adults, and the elderly should foster a brain-health labyrinth adopting a concept of "cradle to grave life-course approach" targeting brain and heart for cognitive health and dementia prevention in India. With India's mobile users to be estimated as more than 500 million, m-health should be channelized to create brain-health awareness and to disseminate effective cognitive health messages for wider targets in our society. Albeit the negative impact of the NIH consensus report, renewed optimism for HBA strategies has been reflected by a recent study that documented that significant proportion of AD may be preventable. [58] The study suggested that the biggest modifiable risk factors for AD were, in descending order of magnitude, low educational attainment, smoking, physical inactivity, depression, mid-life hypertension, diabetes and mid-life obesity. Together, up to half of AD cases worldwide were potentially attributable to these risk factors. Thus these risk factor interventions could potentially have a dramatic impact of AD prevalence over time.

The future for preventive strategies for dementia will be to implement intervention programs that take into account both the life-course model and the multifactorial nature of dementia. [59] There is a critical need to significantly expand global efforts for multinational research infrastructure to obtain an evidence base for multi-domain interventions and HBA strategies for a breakthrough solution to delay the onset of symptoms of dementia and/or AD, slow its progression, and eventually prevent the disease. The life-course approach model include high educational attainment in childhood and early adulthood, active control of vascular factors and disorders over adulthood, and maintenance of mentally, physically, and socially active lifestyles during middle age and later in life. In this respect, the European Dementia Prevention Initiative (EDPI), an international collaboration, looks at the various methodological inconsistencies and challenges in designing dementia prevention trials. [60] The EDPI now include three large ongoing European trials: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Prevention of Dementia by Intensive Vascular Care, and multi-domain Alzheimer Prevention study with focus of dementia research to develop interventions to prevent or delay the onset of dementia as well as identifying special high-risk populations who could be targeted in intervention trials. Such international collaboration aiming to improve strategies for preventing dementia will be a step forward from knowledge to action that could provide robust evidence on dementia or AD prevention.


  Conclusion Top


There is a recurrent theme in a growing body of literature that has pointed out moderately strong evidence to support the association of modifiable vascular, behavioral and lifestyle risk factors with cognitive impairment or AD/VaD. The future would be convincingly shown by designing dementia prevention trials and clinical therapeutic trials based on a life-course model. Such trials should meticulously address methodological inconsistencies and challenges, and promote an international collaboration. The proactive brain-healthy lifestyle needs to be started at the earliest of ages, beginning in the womb, and to be prioritized across the entire lifespan. Such early to mid-life preventive neurology strategies can turn into a freeway leading to a life free from dementia at old age. Thus, dementia will not be a destiny inescapably linked to aging, and HBA strategies could alter brain's cognitive and emotional trajectory to one of a positive, creative, healthy and successful brain aging thus keeping dementia at bay.

"When meditating over a disease, I never think of finding a remedy for it, but instead a means of preventing it"

-Louis Pasteur; 1884

 
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Introduction
Shifts in Thinki...
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Healthy Brain Ag...
Dementia Risk Pr...
The Future Chall...
Conclusion
'Life at the Ext...
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