Executive decline and dysfunction precedes declines in memory: the Women's Health and Aging Study II

Abstract

Background: Understanding preclinical transitions to impairment in cognitive abilities associated with risks for functional difficulty and dementia. This study characterized in the Women's Health and Aging Study (WHAS) II 9-year declines and transitions to impairment across domains of cognition.

Methods: The WHAS II is an observational study of initially high-functioning, community-dwelling women aged 70-80 years at baseline. Random-effects models jointly compared rates of decline, and discrete-time Cox models estimated hierarchies of incident clinical impairment on measures of psychomotor speed and executive function (EF) using the Trail Making Test and in immediate and delayed verbal recall using the Hopkins Verbal Learning Test. Patterns of transition were related to incidence of global cognitive impairment on the Mini-Mental State Exam (MMSE).

Results: Mean decline and impairment occurred first in EF and preceded declines in memory by about 3 years. Thereafter, memory decline was equivalent to that for EF. Over 9 years, 49% developed domain-specific impairments. Risk of incident EF impairment occurred in 37% of the sample and was often the first impairment observed (23.7%), at triple the rate for psychomotor speed (p < .01). Risk of immediate and delayed recall impairments was nearly double that for psychomotor speed (p values <.01). Incident impairment in EF and delayed recall was associated with greater risk for MMSE impairment.

Conclusions: Executive dysfunction developed first among nearly one quarter of older women and was associated with elevated risk for global cognitive impairment. Because EF declines preceded memory declines and are important to efficient storage and retrieval EF represents an important target for interventions to prevent declines in memory and MMSE both of which are associated with progression to dementia.

Figure 1.

Mean rates of decline across cognitive domains, including the Trail Making Test, Part A (dotted line); HVLT immediate recall (dashed and dotted line); HVLT delayed recall (solid line), and the Trail Making Test, Part B (long dashed line), from univariate random-effects models.

Figure 2.

Hazard ratios and corresponding 95% confidence intervals examining risk for incident impairment on each cognitive test, based on a multivariate discrete-time survival model, adjusting for age, education, race, and number of chronic diseases. The Trail Making Test, Part A, served as the reference test.

Figure 3.

Proportion of the sample remaining cognitively intact over time for each cognitive test from the multivariate discrete-time Cox proportional hazard models, based on a mean age of 73.8 years, mean education of 13 years, and average of 1.5 chronic diseases.