Maintaining and Measuring Mental Wellness – Scientific Background

Cognitive Decline

Aging society is a general tendency in Europe as well as in the United States. The number of people belonging to the population aged 65 or over has tripled in the last 50 years and this tendency is estimated to continue in the next 50 years [1]. Dementias are more frequent among women, some form of dementia occurs in 11% of men and 16% of women aged older than 71. Data on the prevalence of dementia are varying but consistent in the increasing prevalence of the disease in older age. About one third of people above 85 years of age are affected [1]. The health care of patients imposes a more and more serious social and financial burden in aging society.  Total payments for health care, long-term care, and hospice for people with AD and other dementias only in the US are projected to increase from $203 billion in 2013 to $1.2 trillion in 2050 (in 2013 dollars) [1].

The most frequent form of dementias is Alzheimer disease, which is responsible approximately for the 60-70% of the cases. Alzheimer's disease results from a combination of genetic, lifestyle and environmental factors that affect the brain over time. Although the causes of Alzheimer's are not yet fully understood, its effect on the brain is clear. Alzheimer's disease damages and kills brain cells (plaques: collection of beta-amyloid on the outside of brain cells). Short term memory impairment is the first sign of the disease. The second most frequent type is vascular dementia, which accounts approximately for 30% of the cases in western countries, however in some countries as in Japan this figure can be much higher (~50%). Vascular dementia results from conditions that damage the brain's blood vessels, reducing their ability to supply your brain with the amounts of nutrition and oxygen. In vascular dementias initial cognitive symptoms can be divers including memory, executive function and attention impairments or general slowing in thinking. Executive functions (e.g.: planning, mental flexibility) are affected first in frontotemporal dementias. Attention can be affected relative early in all forms of dementias. It is important to note that in the later phase (i.e. severe dementia) the symptoms of the different types of dementias are very similar. 

The decline of cognitive functions is an age-related process that affects everybody above the age of 40, but it does not reach an abnormal level in every person.  The early signs of having a higher risk for a pathological decrease in cognition are called Mild Cognitive Impairment (MCI) [2], in this state conversion to dementia is much higher (>10-15% / year) compared to healthy elderly people. The importance of recognizing the population at risk is underlined by scientific data showing, that treatment initiated in the early phase can prolong this phase, and can prolong the ability for independence [3]. 

As there is no effective drug therapy for MCI or dementias, the focus is on prevention at the moment. As Norton et al. [4] showed the major contributing factors to Alzheimer dementia are low education,  vascular risk factors (e.g.: physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. Based on these results and other findings emphasizing the importance of cognitive activity [5–8] we can conclude that cognitive training and physical activity are the best options to prevent dementia at the moment. In the United States there are websites for cognitive training (Lumosity, Happy Neuron), and there have been scientific publications about their effectiveness [9] but in the European Union similar sites are still scarce and not widely known. 

Measuring Cognitive Functions (“Measuring Mental Wellness”)

Since there is no effective treatment for dementias, the early detection of symptoms and the identification of methods for slowing the progression of the disease have been the main focus in the last few years. At the same time, the transitory condition between physiological aging and dementia known as MCI has gained a significant focus of interest. In addition to the preserved global cognitive functions and everyday activities, this means the mild impairment of cognitive skills objectivised by neuropsychological tests [2]. This is a significant process and the change from physiological to pathological aging identifies its start while the development of mild dementia identifies its end. Within this interval the severity and type of involvement determinates the distribution and degree of symptoms.

The clinical significance of the pre-disease conditions is based on the increased conversion rate of affected patients compared to the average. While dementia occurs annually in 1-4% of average elderly population, this rate is 10-15% in case of mild cognitive impairment [10,11]. In view of the above it is understandable that several studies target the symptoms and differences from the average population that are closely linked to the development of dementia and therefore assist the early diagnosis. 

Several recent studies have demonstrated that brain volumes measured by MRI, especially the volume of the temporal lobe structures as the hippocampus can differentiate between patients with Alzheimer’s disease, patients with MCI and healthy subjects [12,13]. In addition, more and more studies have demonstrated that volumes and thickness of temporal structures predict the later development of Alzheimer’s disease in patients with mild cognitive impairment [14,15], in other words these brain volumes can identify subjects at risk. The major drawback of MRI is its high costs, and low availability, therefore it is not suitable for screening at the moment. In addition to brain imaging technologies, the predictive strength of neuropsychological tests such as the Paired Associates Learning (PAL) test has also been demonstrated by several studies [16–18]. Neuropsychological testing is much more cost-effective than imaging; however its screening capabilities are still limited by the required expertise by trained psychologists or psychiatrists.

We believe that cognitive games can be useful tools in monitoring the early signs of cognitive decline. Compared with MRI and neuropsychological testing, the benefits of computer games are their accessibility, their cost-effectiveness, and the fact that no special expertise is required. Due to these factors cognitive games have the potential to monitor the cognitive status much more frequently than imaging or neuropsychological testing, and to compare the results of the subjects to their previous achievements. However correlation studies with MRI examinations and neuropsychological testing are still needed to validate the results of the cognitive games. In addition we would like to emphasize that computer games can only be appropriate tools of general screening, they are not appropriate for diagnosing and therefore they cannot replace the detailed neuropsychological investigation in clinical practice.

Brain plasticity and cognitive training to prevent cognitive decline (“Maintaining Mental Wellness”)

Aging brain retains a lifelong capacity for plasticity and adaptive reorganization. Brain plasticity or in other words synaptic plasticity refers to changes in neural pathways and synapses which are due to changes in behavior, environment and neural processes, as well as changes resulting from bodily injury [19]. In this framework cognitive training can be viewed as a kind of behavior that changes neural pathways and synapses in the brain. In the last decade a lot of evidence was accumulated showing that cognitive training, or “mental fitness” can prevent, or at least delay the onset of cognitive decline or dementias [7,20]. 

One decade ago Verghese et al. [21] found that engaging in leisure activities decrease the risk of dementias in elderly. Later McNab et al. [22] found direct connection between mental activity and brain plasticity by showing that cognitive training was associated with changes in both prefrontal and parietal dopamine D1 receptor binding profile. Anguera et al. [23] used a custom-designed 3D video game to train elderly subjects, and found that the training resulted in performance benefits even in untrained cognitive control abilities such as sustained attention and working memory, which improvements persisted even 6 months after training. They confirmed their results by electroencephalography (EEG), and “highlighted the robust plasticity of the prefrontal cognitive control system in the aging brain”. 

In the last decade several further studies showed that cognitive remediation therapies can be effective even in risk groups, namely in people with Mild Cognitive Impairment or mild Alzheimer Disease [5,6,8,9].

Games in the M3W Project – “Maintaining, Measuring and Entertaining”

The focus was on the measuring and maintaining capabilities when we developed the Cognitive Games in the framework of the M3W project. They improve and test attention, executive functions (planning, mental flexibility, problem solving, decision making), memory (visual span, visuospatial memory, working memory), and language functions. Furthermore we found it very important to develop entertaining games, since involving a broad range of people, what makes them really effective as measuring and developing tools. The R&D challenge was to find the proper balance between validated tests and entertaining solutions.

The objective of the project was to develop a mental wellness toolset for self usage (i.e. for the individuals and their families), and only to a lesser extent for the medical experts (psychiatrists, psychologists, carers, etc.) Our goal was to measure and visualize mental changes, tendencies in an entertaining way, and to give indications, a sort of reports, to the effected persons and their relatives or friends that it is advisable to visit an expert. Our ambition was to compare one's mental wellness to their own past mental wellness conditions (in relative values). The other important mission of the project was that the same games can be used to improve or at least preserve cognitive functions in elderly.