Rates and risk factors for progression to incident dementia vary by age in a population cohort

Objective: To estimate rate of progression from normal cognition or mild impairment to dementia, and to identify potential risk and protective factors for incident dementia, based on age at dementia onset in a prospective study of a population-based cohort (n = 1,982) aged 65 years and older.

Methods: Following the cohort annually for up to 5 years, we estimated incidence of dementia (Clinical Dementia Rating ≥1) among individuals previously normal or mildly impaired (Clinical Dementia Rating 0 or 0.5). In the whole cohort, and also stratified by median onset age, we examined several vascular, metabolic, and inflammatory variables as potential risk factors for developing dementia, using interval-censored survival models.

Results: Based on 67 incident cases of dementia, incidence rate (per 1,000 person-years) was 10.0 overall, 5.8 in those with median onset age of 87 years or younger, and 31.5 in those with onset age after 87 years. Adjusting for demographics, the risk of incident dementia with onset age of 87 years or younger (n = 33) was significantly increased by baseline smoking, stroke, low systolic blood pressure, and APOE*4 genotype, and reduced by current alcohol use. Among those with dementia with onset after 87 years (n = 34), no risk or protective factor was significant.

Conclusion: Risk and protective factors were only found for incident dementia with onset before the median onset age of 87 years, and not for those with later onset. Either unexplored risk factors explain the continued increase in incidence with age, or unknown protective factors are allowing some individuals to delay onset into very old age.