engleski

Epidemiologicial Investigations of Alzheimer's Disease

Clinical neurologists gained important information from neuroepidemiological research, that has been increasing in its extension and importance in the last decade and greatly contributing to the rapid progress in our understanding of the causes, risks and pathomechanisms of many neurological disorders and diseases. The epidemiological studies have substantially supported clinical, laboratory and experimental research in the domain of neurological sciences, introducing new possibilities for early diagnostics, giving impulses for optimal management, therapy and efficient prevention of diseases regarded earlier as a fate. The best examples for this are cerebrovascular disorders, epilepsies, multiple sclerosis, but also, among others, Alzheimer's disease (AD). The concept of Alzheimer's disease and "senile dementias" has been changing from the fatalistic, degenerative, concept, through a unitary concept of senile dementias of the Alzheimer`s type (SDAT), to the presently broadly accepted concept of distinguishing the primary and secondary degenerative from the vascular and secondary symptomatic, potentially treatable dementias. Worldwide neuroepidemiological investigations have been critically analyzed for sometimes contrasting results obtained regarding the methodological problems. So, the methodologies of epidemiological investigations are being constantly improved, taking into account past experience, new development and changed concepts of diseases. On the ground of many studies most of the leading researchers in the field agree, that the age is a single most important risk factor for dementias of all kinds. The prevalence of dementias rises exponentially, and doubles every five years, in the age groups between 65 and 85. It has been questioned, whether the AD is a normal consequence of aging: most of the investigators refuse accepting such a hypothesis, believing that a combination of factors, including genetic predisposition and certain environmental influences, allow the manifestation of the disease. In most, but not all studies, investigating the factor gender, women seem to be at greater risk for dementia, particularly for AD. In spite of these statistical data, the reasons for this are further investigated, since some other social or medical factors could be responsible for this phenomenon. Many of older and more recent studies agree that low education is a risk factor for both AD and vascular dementia. This fact should be however investigated, whether either socioeconomic (nutrition, social condition) or sociocultural factors (life-style, differences in mental activity, lower-grade occupation) could be really responsible. A family history of dementia has been recognized as an important factor, esp. in cases with early appearance. The presence of APOE 4 has been accepted as a risk for developing AD. The factor of race has been found in some studies as relevant, while in recent studies it seems that there are no sure racial differences for the predisposition for AD. Hypertension in mid-life and hypotension in very old age, could be according to some studies, a risk factor, as well as social withdrawal and physical inactivity, diabetes, malnutrition, and exposure to solvents. Head injury with a loss of consciousness for a long time has been suspected as a risk factor for AD ; new investigations do not however accept the results of such studies as relevant. Also controversies exist in regard to thyroid disease, exposure to anesthesia or to blood transfusions, herpes infections and stomach ulcers, suspected in some studies to be risk factors for AD. The role of aluminum exposure has been rejected on the ground of critical analyses of previous studies, having itself quite different clinical course than AD. Some factors have been found as possibly "protective", like: postmenopausal estrogen use, use of non-steroid antiinflammafory drugs, APOE e2 allele and cigarette smoking. Although the last has been indeed recently proved in monozygotic twins, possibly through some so far unknown mechanism of nicotine, the general protective action of cigarette smoking is highly challenged, at least in regard to its known influence on cerebrovascular processes and its role in the pathogenesis of vascular dementia. Although for a long time the dementia with Levy bodies (D/LB) was clinically considered as a non specific variant of AD, nowadays it is clear that it has specific genetic and clinical characteristics. Also, there have been found new genetic factors responsible for some kind of predisposition for the appearance of AD. In spite of many thorough epidemiological studies in the field of dementia research, it is evident that we are now only at the beginning, but of the right route, which leads to the deeper understanding and accomplishments of mastering the responsible factors relevant for the occurrence of Alzheimer's disease and dementias at large. Search for the medical treatment will be the more efficient, the better we know the different Varieties of the disease, leading to future better classification of dementias, including various specific etiologic or risk factors. Although we will probably find more specific risk or protective factors, from the clinical point of view, it is evident already now, that the demential, whether AD or D/LB, are a complex problem with multiple inherited and environmental factors, probably operative mutually synergistically or antagonistically, in various intensities and modalities, in different varieties of the dementia - disease complex. Already now it is sure that avoidance of some risks and the appropriate, healthy life-style are protective factors in most, if not in all kinds of dementias. The future neuroepidemiological investigations, supported by present experience and new laboratory, genetic and biochemical possibilities, could in due time lead not only to new discoveries, but also to new concepts of complex management, including medical therapy, behavioral, social or other influences, changing the risky behavior of Various kinds. Therefore the earlier proposed projects of investigations in the Region of Alps-Adria get new importance and significance.

neuroepidemiology; dementias; Alzheimers disease; risk factors; protective factors

Proceedings of the 36 International neuropsychiatric symposium ; Pula, Hrvatska