Cognitive decline affects a large portion of Quebec seniors which can have troubling consequences for these seniors along with their loved ones. Indeed, more than 500,000 people are affected by a neurocognitive disorder in Canada according to the Alzheimer Society of Canada. This statistic will almost double in the next 10 to 15 years[1]. Unfortunately, the prevalence of neuro-cognitive disorders is rising rapidly in the community and there is very little to offer to this population.

In addition, the impact on the community is very important. Indeed, for each person affected, there are one to three caregivers who invest in time and care with immense socio-economic impacts. It is even estimated that one in five Canadians has already acted as a caregiver for someone with cognitive impairment within their lifetime[2].

The costs related to Alzheimer’s disease and neurodegenerative diseases are $8.3 billion annually in Canada (2011) and are expected to reach $293 billion by 2040, according to Canada’s Standing Senate Committee on Social Affairs, Science and Technology.

In about 70% of cases of neuro-cognitive disorders, Alzheimer’s disease is found to be the cause. Nearly 50% of people with a cognitive disorder, including Alzheimer’s disease, are also diagnosed at a too-advanced stage of the disease[3],[4]. As it is progressive, the manifestations of the evolution of this pathology vary from one person to another and can last between eight and ten years, or even more. In all cases, the affected individual gradually loses their cognitive function and develops a relationship of dependence on those closest to them to carry out the activities of their daily life. The diagnosis of Alzheimer’s always represents a death sentence and inevitably triggers, in the caregiver, what is called white mourning, as the personality of the person affected changes and no longer corresponds to that which has been known before[5].

Even if we note that Alzheimer’s is a very complex pathology on the biological level which results from several physiopathological processes, the pharmaceutical industry is still and always looking for a monotherapy (a single drug) that can change the future of this terrible disease. The drugs developed to try to reverse the process of cognitive disorders are numerous, but the negative clinical studies number in the hundreds. Only a tiny minority have shown benefits, which are, however, marginal. Moreover, it costs approximately $359 million to successfully bring a drug used in the treatment of cognitive disorders to market, from start to finish[6]. Imagine all that we could do in prevention with this amount!

Interestingly, degenerative brain changes can occur up to 25 years before the first symptoms appear. It is well known that unhealthy behaviors such as smoking, physical inactivity, social isolation, alcohol abuse, and suboptimal diet are modifiable risk factors for dementia. We also know that there are many associations between Alzheimer’s disease and cardiovascular health, often resulting from poor lifestyle habits[7].

Systematically optimizing lifestyle habits and nutritional status in at-risk individuals could most certainly slow down, possibly even eliminate, the likelihood of the onset of Alzheimer’s, dementia, as well as many other well-known chronic metabolic diseases (cardiovascular disease, diabetes, high blood pressure, etc.). This would inevitably result in a net cost reduction in the healthcare system.

Currently, there is no integrated care structure in the healthcare system in Quebec that offers to slow down, or even reverse to varying degrees, an individual’s cognitive decline in order to reduce the burden on the healthcare system, and, for the most part, to optimize the well-being of the affected individual. However, multiple studies demonstrate the positive effect of a multimodal approach based on the optimization of lifestyle habits and nutritional status on cognitive status. This type of approach is referred to as optimization and metabolic enhancement approaches to counter neurodegeneration[8].

A few key studies, namely the FINGER[9] study, the PREDIVA[10] study, the NUN[11] study, the Hawaii Dementia Prevention trial[12], the SINGER[13] study, the multimodal study on metabolic enhancement to counter neurodegeneration[14] as well as the work of Dr. Dale Bredesen in the United States who is at the origin of the ReCode® program[15] prove that supporting the individual in adopting healthy lifestyle habits in the hope of controlling or even reversing their metabolic risk factors is very beneficial in the prevention of dementia. Other research projects are even currently underway around the world to concretely study the implementation of structured programs with a multimodal approach aimed at improving lifestyle habits in order to slow down cognitive decline[16]. Dr. Michael Nehls also offers a vision he has called the “unified theory of Alzheimer’s disease” where he encourages a reframing of the scientific literature to highlight several possible causes of cognitive decline, most of which fall under the category of lifestyle habits, in order to bring about a paradigm shift when we think about this pathology[17].

Some researchers behind these few landmark studies identified different cognitive decline subtypes and developed a plan focusing on 7 modifiable factors: diet, physical activity, sleep, stress management, cognitive stimulation, intrinsic functions of detoxification and homeostasis, as well as targeted supplementation. Various scientific data are now available and demonstrate the benefit of addressing these spheres of health to prevent and improve well-being in cognitive decline.

The strength of a multimodal approach (i.e. focused on several interventions at the same time) and also personalized from a perspective of metabolic enhancement to counter neurodegeneration is to be able to structure the interventions in a personalized way based on a large collection of data from various spheres: metabolic, clinical, anthropometric, volumetric (MRI of the brain, if accessible), from the anamnesis (the history of the current illness), and from longitudinal life history (all events in the past that have an impact on the physiology of the present illness). It goes without saying that these elements are rarely recorded in detail in the context of current conventional care in Quebec, but are nevertheless essential to understanding the etiology of cognitive decline and to prevent further decline by addressing disturbed physiological processes.

Contrary to the philosophy of donating a molecule for a specific pathology in the hope of controlling all the symptoms of the disease without success, the global and functional approach with a preventive aim is intended to be a personalized approach making it possible to work on the physiological terrain that underlies the probability of developing pathological lesions with the aim of eliminating them, slowing them down and/or promoting the regeneration of certain damaged tissues.

This way of seeing things is quite recent and stems from the reframing of scientific literature. Indeed, many studies have pointed to characteristic subgroups of the disease. A researcher, Dr. Dale Bredesen[18], categorized these subtypes. They are as follows:

Type 1 (inflammatory)

Inflammation is an acute healthy and protective mechanism, which has the objective of recognizing, destroying, and eliminating all the substances which are foreign to it while promoting the healing of the tissues of our body that have been injured. However, when the inflammation becomes uncontrolled, or chronic, that is where the damage to the body becomes noticeable. Chronic inflammation is caused by exposure to constant and unhealthy attacks on the body, especially through behaviors (e.g., poor quality food, smoking, abundant pollution, etc.). Chronic inflammation is prevalent through cardiovascular disease, diabetes[19], depression [20] [21] and Alzheimer’s disease, among others. In these cases, the inflammation comes from different factors from the environment and life behaviors. Indeed, we have an immune system inside our brain itself which, when activated, exacerbates the presence of 𝛃-amyloid plaques and promotes the accumulation of the tau protein associated with neurofibrillary tangles[22],[23]. Chronic inflammation encourages the brain to destroy synapses faster than it creates them[24]. It is therefore quite logical and even crucial to take an interest in inflammatory markers and the functioning of the immune system if we wish to improve our interventions in the face of Alzheimer’s disease and prevent families from seeing their loved ones have their memories stolen too early. We must develop effective interventions that address the underlying causes and factors that promote chronic inflammation. It is also recognized that the likelihood of suffering from a cognitive disorder with “type 1” etiology tends to be inherited, as it is common in people who carry one or two ApoE4 alleles (ApoE itself is considered a pro-inflammatory gene)[25]. These people have an exaggerated inflammatory reaction against simple attacks and will be more at risk of developing Alzheimer’s disease and cardiovascular disease. Mitigating chronic inflammation by managing and reversing its causes is therefore paramount for this population.

Type 1.5 (glycotoxic)

Type 1.5 is the meeting between type 1 and type 2. It is a type where there is the presence of brain inflammation combined with a lack of neurotrophic and trophic support (see next section). We see the deleterious effects of chronic hyperglycemia on the brain by contributing to inflammation and by promoting the glycation of molecules (impairment of functionality going as far as the destruction of non-functional cells, through the excess of sugar).

Type 2 (atrophic)

Trophic and neurotrophic factors refer to what nourishes tissues, organs, and neurons. The atrophic type here, therefore, refers to a lack of factors nourishing these different structures. This results in a cascade where the end consequence is a “drying up” of brain synapses as the brain begins to destroy synapses faster than it creates them[26]. Two of these trophic factors are brain-derived neurotrophic factors (BDNF for Brain-Derived Neurotrophic Factor), as well as nerve growth factors or NGF for Nerve Growth Factor. The BDNF factor plays a crucial role in cognition, learning, and memory formation. It has an important role in new learning as well. Low levels of BDNF in the brain have been associated with higher incidences of Alzheimer’s disease[27]. Unlike inflammatory type 1, atrophic type 2 does not have such problematic inflammatory markers (sometimes they are even normal), but impaired glucose metabolism, i.e., chronic resistance to insulin or too low a level of insulin (as in an individual who may be malnourished, for example) leading to a loss of trophic support[28]. We also note the absence of the trophic state of male and female sex hormones and thyroid hormones in several cases. This reduction in trophic support is consistently seen in Alzheimer’s disease type 2. Type 2 is also more common in people who carry one or two copies of the ApoE4 allele, but symptoms tend to appear around ten years later than those of inflammatory disease type 1.

Type 3 (toxic)

Type 3 is an etiological subtype of cognitive decline completely different from the others. It tends to occur in people who carry the ApoE3 allele rather than ApoE4. It affects individuals at a younger age, usually between their late 40s and early 60s. It is associated with increased exposure to environmental toxins that negatively impact brain function, such as heavy metals and mold (mycotoxins).

Type 4 (vascular)

Type 4 is of vascular etiology. Arterial blockage caused by a buildup of cholesterol can cause reduced blood flow to the brain, which ultimately deprives the brain of oxygen and essential nutrients. The brain is an extremely vascular tissue, which means that it needs large quantities of oxygen and even slight damage to the vascular supply can cause significant damage to the cells. A lack of oxygen in the brain leads to hypoperfusion (low blood flow) and compromises the blood-brain barrier, allowing harmful substances to leak in and further damage neurons[29]. The cerebral vasculature is extremely important as it is one of the ways the body eliminates beta-amyloid buildup.

Type 5 (traumatic)

Alzheimer’s disease type 5 is induced by a series of traumas that disrupt the normal functioning of the brain, in particular its ability to learn and think. Certain types of head injuries and their frequency can increase the risk of developing Alzheimer’s disease years after the injury[30]. One of the most landmark studies showed that people with a history of moderate traumatic brain injury had a 2.3x higher risk of developing Alzheimer’s disease than older adults with no history of traumatic brain injury and that people with a history of severe head traumas had a 4.5x higher risk[31].

 

The health of seniors should be a priority for the country because we know that the burden on the health system is immense. It is clear that a well-structured preventive approach has the power to make a significant difference as much in the individual and their loved ones, as in the healthcare resources that will prove to be less consumed. An open mind is necessary in regard to new ways of preventing and reversing chronic diseases such as neurodegenerative diseases. A gain in autonomy, a reduction in hospitalizations, an improvement in known chronic diseases, a reduction in the consumption of medication, and a less dependent relationship with caregivers, are all elements that are likely to be improved with optimal support and lifestyle habits that promote brain health. When will there be many integrative clinics in the province that will finally allow this kind of care?

 

 

Anne-Isabelle Dionne, MD

Dr. Dionne has been a general practitioner since 2014 and practices in intensive care at the Honoré-Mercier Hospital in St-Hyacinthe as well as in an FMG on the South Shore of Montreal. In 2018, she founded a preventive medicine center specializing in supporting people suffering from various health problems in improving their daily lifestyle habits through diet, physical activity, stress management, and sleep. Le Centre Axis is an NPO that offers multidisciplinary preventive care to the general population wishing to improve their health and prevent or reverse a known chronic disease while reducing the need for associated medication. The services of Le Centre Axis can be dispensed remotely through telemedicine. To contact us: 514-953-2947 or info@centreaxis.ca.

Cynthia Gariepy, ND

Cynthia Gariépy has been a certified naturopath since 2003 and practices in private clinics as well as at the Axis Center.

 

Article initially published in Vitalité Québec

 

 

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