Background: The purpose of this study was to test nongenetic factors that might explain discordance for dementia in monozygotic twin pairs. Risk factors included education, engaged lifestyle in midlife, and early life circumstances indexed by tooth loss, short adult height, and parental social class.
Methods: Data are from the HARMONY study, including members of the Swedish Twin Registry age 65 and older and alive in 1998, who were screened and assessed clinically for dementia. Analyses included a case-control design to evaluate the risk factors and a co-twin control design that permits testing nongenetic risk factors while controlling for genetic influences. Case-control analyses included 310 dementia cases and 3,063 nondemented controls. There were 106 monozygotic twin pairs discordant for dementia. Risk factors were assessed independently by the Swedish Twin Registry three decades previously.
Results: Case-control findings showed that history of tooth loss before age 35 and low educational attainment were significant risk factors for Alzheimer's disease, with short adult height also contributing to risk for total dementia. In co-twin control analyses, only history of tooth loss before age 35 was a significant risk factor for Alzheimer's disease, whereas low educational attainment also contributed to risk for total dementia and lack of physical exercise to risk for non-Alzheimer's dementias.
Conclusions: Potentially modifiable risk factors from early and midlife, with a cumulative detrimental effect on the brain, contribute to risk of dementia. Based on the association with tooth loss, further investigation of inflammatory load as a risk factor for Alzheimer's disease is warranted.