Heterogeneity in risk factors for cognitive impairment, no dementia: Population-based longitudinal study from the Kungsholmen Project

objectives: The objectives of this study were to investigate the relation of vascular, neuropsychiatric, social, and frailty-related factors with "Cognitive impairment, no dementia" (CIND) and to verify their effect independently of future progression to Alzheimer disease (AD). Methods: Seven hundred eighteen subjects aged 75+ years who attended baseline, 3- and 6-year follow-up examinations of the Kungsholmen Project, a Swedish prospective cohort study, were studied. CIND was defined according to the performance on the Mini Mental State Examination. Potential risk factors were collected at baseline and clustered according to four research hypotheses (frailty, vascular, neuropsychiatric, and social hypothesis), each representing a possible pathophysiological mechanism of CIND independently of subsequent development of AD. Results: Over a mean 3.4 years of follow up, 82 participants (11.4%) developed CIND. When the population was subsequently followed for a mean of 2.7 years, subjects with CIND had a threefold increased risk to progress to AD. After multiple adjustments, including adjustment for the development of AD at the 6-year follow up, risk factors for CIND were hip fracture, polypharmacy, and psychoses. Conclusions: The results suggest that not only the AD-type neurodegenerative process, but also neuropsychiatric- and frailty-related factors may induce cognitive impairment in nondemented elderly. These findings may have relevant preventive and therapeutic implications.