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  • ETH1: What is the severity level of the condition that IGG is directed to?
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What is the severity level of the condition that IGG is directed to?

Authors: Plamen Dimitrov, Anelia Koteva

Internal reviewers: Pseudo99 Pseudo99

Technological advances in medicine and healthcare over the past decades have increased the life expectancy of the population in industrialized countries, shifting the focus of public attention from communicable to chronic non-communicable diseases, including dementia.


According to WHO data for 2010, the approximate number of people suffering from dementia worldwide is estimated at 35.6 million people, with the figure expected to double by 2030 reaching 65.7 million people and more than triple by 2050 (115.4 million people)[1]. The total number of new cases of dementia each year amounts to 7.7 million, which makes one case every 4 seconds[2]. More recent figures, but in a regional context, are provided by the Alzheimer’s Association, where 5.2 million Americans from all age groups are reported[3] to have Alzheimer’s disease for 2013 in the USA alone. The same report states that 1 in 9 Americans over 65 years of age, respectively, one-third of the persons aged 85 and older suffer from the disease. Among the total number of individuals covering the criteria[4] for AD diagnosis, the distribution is as follows: 4%  - below 65 years of age, 13% - aged between 65 and 74 years , 44% - 75-84 years and 38% - aged 85 and over. In terms of gender distribution, females prevail over males (about two-thirds of women and one third of men).


Dementia is not isolated from individuals alone; rather, it affects their family members, relatives and friends by involving significant healthcare and social care resources for persons with dementia, thus influencing the general public as well. Costs that society bears in health, economic and social  dimensions are substantial, representing a huge burden on the budget. According to the WHO report, the global costs associated with dementia reached the impressive figure of USD 604 billion in 2010 (corresponding to 1.0% of the aggregated worldwide GDP)[5], of which the share of direct medical costs, measured in high-income countries, amounts to only 15%. The rest, being a much more, are indirect costs.


Therefore, the high morbidity of dementia on a global scale, including Alzheimer’s disease, combined with the high cost of this condition in all spheres of public life, the growing need to provide long-term care for the persons with dementia and the related social isolation and stigmatization to cope with, make dementia a global challenge, placing it among public health priorities.


Alzheimer’s disease, the most common cause of dementia, belongs to the group of neurodegenerative diseases characterized by unknown etiology, hereditary predisposition and gradual progression over many years. The disease is of great medical and social importance with unnoticeable onset and irreversible course, being incurable at present, leading to death.


In accordance with the most common description used by clinicians, the disease is known to progress slowly, lasting on average 10-12 years from the time of diagnosis. Early signs are often ignored by the patient and his/her relatives, being mistakenly attributed to aging, thus making it difficult to correctly and adequately diagnose. The most common symptom is the short-term memory loss expressed in difficulties in remembering or reminding recent events and inability to acquire new knowledge and memories. As the disease progresses, the clinical signs become more obvious, being complemented by spatial and temporal disorientation, confusion, mood swings, depression, irritability, aggression, behavioral disturbances, abstract thinking problems, difficulties in speech and loss of long-term memory as well as complete personal degradation with worsening social skills, causing permanent disability and inability to lead full-value life. Finally, organ functions gradually diminish and death occurs.


In order to classify individuals with memory impairment that normally does not progress to dementia, in 1962 V.A. Kral proposed the term “benign senescent forgetfulness”[6]. In addition to the cognitive deficit remaining stable and not deepening in the course of time, these adults show a slight memory decrease when evaluated by memory tests, without significant deviation from age-related norms.


It is this state of gradual transition from norm to pathology that is identified in the literature as “mild cognitive impairment”. MCI is typical of persons without other neurological, psychiatric, vascular, endocrine, communicable and neoplastic diseases, injuries, drug or alcohol intoxication carrying the potential for such diversions, with the MCI individuals exhibiting memory impairment that is more pronounced than what should normally be expected for a certain age and education level with preserved consciousness and cognitions, and routine daily activities remaining undisturbed.


As noted above, the term makes it possible to distinguish between dementia patients and fake dementia ones as well as those characterized by an isolated cognitive deficit due to physiological aging. The first one is an example of irreversible dementia, while in the other mentioned groups memory deficit remains stable or reversal occurs.


It should be emphasized that mild cognitive impairment is not actually a diagnosis (or a distinct nosological unit); rather, it is a concept for which specialized literature has suggested relevant diagnostic criteria that have undergone modifications over time. The MCI term denotes a preclinical, prodromal stage, not automatically presuming the medical diagnosis of Alzheimer’s disease.


To conclude, mild cognitive impairment causes a slight but noticeable and measurable decline in cognitive status, being associated with an increased risk of developing Alzheimer’s disease in the future. Long-term studies have found that in persons aged 65 and above, the frequency of MCI varies from 10 to 20%[7], and in a small percentage of cases mild cognitive impairment may progress to Alzheimer’s disease or other types of dementia, without it necessarily being so. The creation of this term is important in view of its practical importance as far as it is bound to the likelihood to early diagnose that type of degenerative dementia that allows for the application of a more effective treatment.


[1] According to WHO data for 2010, published in “Dementia: A Public Health Priority”, World Health Organization , 2012, p.2, available at: .

[2] Ibid, p.2., available at: .

[3]2013 Alzheimer’s Disease Facts and Figures”, Report of the Alzheimer’s Association, vol. 9, issue 2, 2013, p. 15, available at: .

[4] The report explicitly states that it is based on estimates and not actual number of cases of dementia diagnosed by a physician, which is due to the impossibility to cover all patients. It is also noted in the report that half of the 5.2 million Americans exhibiting clinical symptoms of Alzheimer’s disease are probably not aware of this fact – author’s note.

[5] See: the WHO Report for 2010: “Dementia: A Public Health Priority”, World Health Organization, p. 25, available at: .

[6] Kral, V., “Senescent Forgetfulness: Benign and Malignant”, Journal of the Canadian Medical Association, February, 1962, vol. 86 (6): 257-260, available at: .

[7] According to the data of Alzheimer’s Association: .

Dimitrov P, Koteva A Result Card ETH1 In: Dimitrov P, Koteva A Ethical analysis In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 24 October 2020]. Available from: