BACKGROUND: There may be important public health implications of increasing our 
knowledge of factors associated with age of dementia onset. The pre-morbid 
personality domain of Neuroticism constituted an interesting and theoretically 
plausible, yet uninvestigated, candidate for such an association. We aimed to 
examine whether midlife Neuroticism was associated with earlier age of onset of 
Alzheimer's disease (AD).
METHOD: This was a case-comparison study of 213 patients with probable AD. 
Detailed clinical information was collected for all patients including age of 
onset of dementia symptoms. One or two knowledgeable informants rated each 
patient's midlife personality retrospectively using the Neuroticism, 
Extraversion, Openness Five-Factor Inventory (NEO-FFI) questionnaire. The 
relationship between midlife Neuroticism and age of dementia onset was evaluated 
using both correlational analysis and backward linear regression analysis.
RESULTS: Midlife Neuroticism predicted younger age of dementia onset in females 
but not in males. The association found in females was independent of pre-morbid 
history of affective disorder.
CONCLUSIONS: This finding and its potential mechanism warrant further 
investigation.