Diabetes, Head Trauma, Marriage, and Dementia
February 1, 2000
Diabetes, Head Trauma, Marriage, and Dementia
Abstracts & Commentary
Sources: Ott A, et al. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999;53:1937-1941; Mehta KM, et al. Head trauma and risk of dementia and AD: The Rotterdam Study. Neurology 1999;53:1959-1962; Helmer C, et al. Marital status and risk of AD. Neurology 1999;53:1953-1958.
Diabetes mellitus type 2 (dm) increases the risk of stroke and persons with stroke are thought to be more likely to develop dementia if they suffer from diabetes. It has been suggested that DM might also be a risk factor of Alzheimer’s disease (AD). Among a community-based prospective cohort study based in the Netherlands, 6370 involved participants were screened for DM and dementia, with an average follow-up period of 2.1 years. In approximately 1100 other cases with no follow-up information, dementia status was culled from medical records.
DM was found to nearly double the age- and gender-adjusted risk of dementia in 692 diabetics. The incidence risk of dementia was highest in those requiring insulin treatment, and lowest among newly diagnosed or untreated mild cases. DM incidence in men or women was about equal, with no clear trend in age. When the likely cause of dementia and other confounders was evaluated, diabetes was found to increase by two-fold the risk of both dementia in general and AD in particular.
The Rotterdam study also addressed the possibility of a relationship between mild head trauma and the development of dementia. This arm of the study included 6645 subjects, age 55 and older, who were free of dementia at the onset. Self-report of past head trauma was obtained from this cohort and incident cases of dementia were determined over the 2.1-year follow-up period. A total of 129 subjects developed dementia over this time. In concordance with some past studies, no increased risk of dementia was found as a function of exposure to head trauma with or without loss of consciousness. In contrast to earlier studies by other groups, possession of the APOE-e4 allele was not found to modify the relationship between head trauma and the development of AD.
A French research team examined the issue of whether marital status affected risk of dementia. Helmer and colleagues divided their cohort of 3675 subjects into groups of married/cohabitant, divorced/separated, widowed, and never married. Helmer et al found the relative risk of dementia was increased among the never married relative to the married individuals, and the risk was specifically associated with AD. The risk of dementia was not significantly elevated among widows and divorced subjects. The results remained significant even after taking into account potentially confounding factors such as educational achievement and wine consumption. The analysis did not permit a firm conclusion to be drawn as to whether never married persons were actually at increased risk or married persons enjoyed some protection against the disease.
Commentary
These results warrant further investigation. One previous indication of a possible association between diabetes and AD came from recent studies showing increased advanced glycosylation end products (AGE) in the brain of Alzheimer’s patients. Increased AGE expression is found in other end organs that are frequently affected by complications in diabetics. While there are many possible explanations for such an association, further work will be needed to confirm this observation.
The lack of an association between head trauma and dementia in this report is not surprising, in that five out of every six studies of head trauma and dementia carried out before 1990 failed to demonstrate just such a relationship. However, more recent work has suggested an additive or even synergistic relationship between head trauma, dementia, and APOE genotype. The negative findings in this case may, in part, reflect differences in the method of ascertainment of head trauma history or another unrecognized confounding factor.
Failure to marry has not been previously implicated as a risk factor for AD. Helmer et al made a valiant effort to measure the subjects’ social involvement independent of marriage, and found that level of social activity did not correlate with dementia incidence. One could postulate similar protective mechanisms for marriage as for higher education. An alternative explanation is that unmarried persons have some underlying personality trait that segregates with the propensity to develop dementia. Whatever the explanation, its somewhat comforting to know that the much-maligned institution of marriage may have benefits above and beyond joint tax returns. —nrr
Epidemiological evidence suggests that the risk of developing dementia:
a. is increased by marriage.
b. is decreased in juvenile-onset diabetes.
c. is decreased by head trauma.
d. is increased among insulin-treated diabetics.
e. is decreased in unmarried diabetics with head trauma.
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