Outcome over seven years of healthy adults with and without subjective cognitive impairment

Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects.

A consecutive series of healthy subjects, aged ≥40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14‐year interval, were studied and followed up during an 18‐year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 ± 9.1 years, was well‐educated (mean, 15.5 ± 2.7 years), and cognitively normal (Mini‐Mental State Examination, 29.1 ± 1.2).

A total of 213 subjects (81.9% of the study population) were followed up. Follow‐up occurred during a mean period of 6.8 ± 3.4 years, and subjects had a mean of 2.9 ± 1.6 follow‐up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined (P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow‐up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9–10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45–0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects (P = .0003).

These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7‐year mean follow‐up interval. Relevance for community populations should be investigated, and prevention studies in this at‐risk population should be explored.