Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology

Background: Alzheimer disease (AD) is the most common cause of dementia. The effect of cerebral infarctions on the likelihood of dementia from AD pathology is not well understood. Methods: The study included 153 deceased Catholic clergy who participated in the Religious Orders Study. Annual evaluations, including 19 tests of cognitive function, were performed to determine a diagnosis of dementia and level of cognitive abilities proximate to death. At autopsy, neuritic and diffuse plaques and neurofibrillary tangles were counted and combined into a standardized summary measure of AD pathology. Number, volume, side, and distribution of old macroscopic infarctions were recorded. Analyses included logistic and linear regression, adjusting for age, sex, and education. Results: The AD pathology score ranged from 0 to 2.93 units, and 54 persons had infarctions. There was no relationship between AD pathology and infarctions ( r = 0.04, p = 0.56). Each unit of AD pathology increased the odds of dementia by 4.40-fold (95% CI = 2.33 to 8.32), and this was essentially unchanged after accounting for infarctions. The presence of one or more infarctions independently increased the odds of dementia by 2.80-fold ( 95% CI = 1.26 to 6.21). There was no interaction between AD pathology and infarctions to further increase the likelihood of dementia ( p = 0.39). The number, size, and distribution of infarctions added to the odds of dementia but also did not show an interaction with AD pathology. Similar results were found in analyses with global cognitive function and five different cognitive systems. Conclusion: Cerebral infarctions independently contribute to the likelihood of dementia but do not interact with AD pathology to increase the likelihood of dementia beyond their additive effect.