Risk Factors for Mild Cognitive Impairment, Dementia and Mortality: The Sydney Memory and Ageing Study

Background: The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years.

Methods: We classified 873 community-dwelling individuals (70-90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline.

Results: Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01-1.14 for MCI; 1.19, 1.09-1.31 for dementia), MCI at baseline (5.75, 3.49-9.49; 8.23, 3.93-17.22), poorer smelling ability (per extra test point: 0.89, 0.79-1.02; 0.80, 0.68-0.94), slower walking speed (per second: 1.12, 1.00-1.25; 1.21, 1.05-1.39), and being an APOE ε4 carrier (1.84, 1.07-3.14; 3.63, 1.68-7.82). All except APOE genotype were also associated with mortality (age: 1.11, 1.03-1.20; MCI: 3.87, 1.97-7.59; smelling ability: 0.83, 0.70-0.97; walking speed: 1.18, 1.03-1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63-5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI.

Conclusion: A core group of late-life risk factors indicative of physical and mental frailty are associated with each of dementia, MCI, and mortality after 6 years. Tests for slower walking speed and poorer smelling ability may help screen for cognitive decline. Individuals with normal cognition are at greater risk of future cognitive impairment if they have a history of MCI.