Medical History and the Risk of Alzheimer's Disease: A Collaborative Re-Analysis of Case-Control Studies

Abstract

In a re-analysis of eight case-control studies on Alzheimer's disease we explored several medical conditions that had previously been suggested as possible risk factors for Alzheimer's disease. History of hypothyroidism was increased in cases as compared to controls (relative risk 2.3; 95% confidence interval 1.0-5.4). Severe headaches and migraine were inversely related to Alzheimer's disease (relative risk 0.7; 95% confidence interval 0.5-1.0). More cases than controls reported epilepsy before onset of Alzheimer's disease (relative risk 1.6; 95% confidence interval 0.7-3.5), especially for epilepsy with an onset within 10 years of onset of dementia. Neurotropic viruses, allergic conditions, general anaesthesia and blood transfusions were not associated with Alzheimer's disease.

Longitudinal evidence of the impact of normal thyroid stimulating hormone variations on cognitive functioning in very old age

“…The finding that the reliable TSH-cognitive performance associations were all positive, both cross-sectionally and longitudinally, may seem at odds with previous studies showing that hypothyroidism (in which TSH values are high) constitute a risk factor for developing dementia at a later stage (e.g., Breteler et al, 1991;Ganguli et al, 1996). It is however not uncommon that the predictive power (both in terms of strength and direction) changes outside normal ranges (e.g., Wahlin et al, 1996) or that the predictive directions are best described as an inverted U-shaped form.…”

On the issue of transmissibility of Alzheimer disease

“…16,32 Early studies focused on the identification of potentially infectious agents. Like in other diseases of unknown origin, slow virus infections were suspected to play a role in AD pathogenesis.…”

“…Numerous studies were conducted with different populations in several countries with various methods, yet no evidence for an association between prior blood transfusions and the risk of AD could be shown. 32,33,39,[43][44][45] However, these studies were prone to recall biases (subjects answers are affected by their memory) as well as to selection biases of the control group (error in choosing the group correctly) to some extent. (Table 1).…”

“…Breteler et al discussed this issue in detail, but until now, no feasible solution has been developed. 32 [When blood transfusions additional literature not covered by the database search. Since epidemiological evidence is scarce, all relevant literature was sought to be included into this review.…”

“…Molecular mechanisms were hypothesized and especially volatile anesthetics were demonstrated to be associated with Aβ production, Aβ oligomerization, Tau formation and Tau phosphorylation as described thoroughly in a review by Papon et al 56 Several observational studies were designed to substantiate these experimental theories with epidemiological data. 32,47,48,[57][58][59][60] Nonetheless, a recent systematic review concluded that, despite the amount of studies available, evidence for an association of anesthesia with AD is Selected were those possibly associated with AD induction by a potentially transmissible pathogen (e.g., viral infections, blood transfusion, cns surgery). Therefore, studies regarding anesthesia, peripheral surgery, life style factors, genetics, etc., which are more abundant, are not shown.…”