Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia

Background: Risk factors for dementia can be divided into those that lead to pathologic insults and those that render the brain more vulnerable to such insults. Dementia prevention strategies need to be informed as to whether to prioritize reducing risk of pathology or to reduce the vulnerability of the brain to pathologic insult. Lower premorbid cognitive ability is associated with both increased vascular risk and reduced cognitive reserve, a measure of brain vulnerability. We investigated differential effects of premorbid cognitive ability on dementia subtypes to clarify which causal pathway was predominant. Methods: A total of 297 cases of late onset dementia were identified from local case registers, born in 1921, and thus may have participated in the Scottish Mental Survey of 1932 (SMS1932). A total of 183 had mental ability scores identified in the SMS1932. A total of 173 of these were matched by birth records to one set of controls (controls1) by date of birth, sex, and district of birth registration. A further set of controls (controls2) was generated additionally matched on paternal occupation. Results: Vascular dementia cases had significantly lower premorbid cognitive ability (OR 0.62, 95% CI 0.41-0.94, for every 10-point increase [0.7 SD] in mental ability score vs controls2), but there was no significant difference in the premorbid cognitive ability of Alzheimer disease cases (OR 1.02, 95% CI 0.82-1.28) vs controls2. Conclusion: Lower premorbid cognitive ability is a risk factor for vascular dementia, but not Alzheimer disease. This suggests its effect acts mainly through vascular pathology rather than brain vulnerability.