Baseline subjective memory complaints associate with increased risk of incident dementia: the PREADVISE trial

Abstract

Background: Subjective memory complaints reflect patient-identified deficits in memory and have been linked to increased risk of future dementia in nondemented (including cognitively intact) older adults.

Objectives: To assess the risk of incident dementia during follow-up for participants in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADVISE) study who reported memory complaints at baseline.

Design: Double-blind, placebo controlled 2×2 randomized controlled trial that transformed into an observational cohort following discontinuation of supplementation in the SELECT parent trial.

Setting: PREADVISE participants were assessed at 130 local clinical study sites in the United States, Canada, and Puerto Rico during the controlled trial phase and were later followed by telephone from a centralized location during the observational phase.

Participants: PREADVISE enrolled a total of 7,547 nondemented men over the age of 60; 4,271 consented to participation in the observational study.

Measurements: Participants were interviewed at baseline for memory complaints. The Memory Impairment Screen (MIS) was administered to each participant at the annual memory screening. Participants who failed the MIS also received a more detailed neurocognitive assessment: an expanded Consortium to Establish a Registry in Alzheimer's Disease (CERADe) neuropsychological battery was used during the RCT, and the modified Telephone Interview for Cognitive Status (TICS-m) was used during the observational study. Participants who failed the second screen were asked to have a memory work-up with a local physician and to share their medical records with PREADVISE. Subgroups of men who did not fail the MIS were also asked to complete the CERADe battery and TICS-m for validation purposes. Additional measures collected include self-reported medical history, medication use, and the AD8 Dementia Screening Test.

Results: After controlling for important risk factors for dementia, Cox proportional hazards regression revealed that men who reported memory changes at baseline had an 80% increase in the hazard of incident dementia compared to men who reported no SMC. Men who reported memory problems at baseline had almost a 6-fold increase in the hazard of incident dementia compared to men who reported no memory complaint.

Conclusions: Memory complaints in nondemented older men predicted future dementia. Men who reported that the changes in their memory were a problem were especially at risk, and the presence of common comorbidities like diabetes, sleep apnea, and history of head injury further exacerbated this risk.

Keywords: dementia; longitudinal cohort; subjective memory complaints.

Figure 1

Kaplan-Meier product-limit estimates of failure probability by baseline memory complaint status. Red (bottom) = No Memory Complaint, Blue (middle) = Memory Change, Green (top) = Memory Problem. Censored observations are indicated with a ‘+’ symbol.

Figure 2

Estimated years to dementia diagnosis based on Cox regression results for hypothetical participants with different risk profiles. All hypothetical participants are white, age 70 at baseline, and have 12 years of education. ‘Comorbidities’ indicates presence of hypertension, diabetes, sleep apnea, and history of head injury.