SAN DIEGO – Subjective memory complaints at study enrollment predicted clinical memory impairment 8 years later in healthy men aged 60 years and older, findings from a large ongoing study showed.
"This suggests the utility of subjective memory complaints for future prevention trials," Erin L. Abner, Ph.D., said at the Clinical Trials Conference on Alzheimer’s Disease.
Dr. Erin L. Abner
She and her associates also found that hypertension, diabetes, black race, and education level emerged as significant risk factors for clinical impairment, while the use of antihypertensive agents and statins emerged as protective factors.
The findings come from centralized follow-up of men enrolled in the PREADVISE (Prevention of Alzheimer’s Disease by Vitamin E and Selenium) trial, which was launched in 2002 as an ancillary to the SELECT (Selenium and Vitamin E in Preventing Prostate Cancer) trial. PREADVISE was designed to assess the effect of vitamin E and selenium on reducing the incidence of Alzheimer’s disease and other neurodegenerative disorders.
The PREADVISE study had four arms: Participants received 400 IU vitamin E per day, 200 mcg of selenium per day, both, or matching placebos. Recruitment began in 2002, and a total of 7,553 nondemented men aged 60 and older participated. In 2008, SELECT was suspended because of an interim futility analysis, and study sites began closing. Two years later, 4,246 PREADVISE participants consented to centralized follow-up by telephone. Of these, 3,701 have been screened to date, said Dr. Abner of the Sanders-Brown Center on Aging and the department of epidemiology at the University of Kentucky, Lexington.
Men were eligible for PREADVISE if they scored at least a 5 on the Memory Impairment Screen (MIS) at baseline. "They received alternating versions of the MIS in subsequent years to minimize learning effects," she said. "If they failed the MIS, they were given the Consortium to Establish a Registry for Alzheimer’s Disease [CERAD] neuropsychological test battery. If their age-adjusted CERAD score was 35 or less, they were referred to a physician for a medical work-up and had their medical records forwarded to us." If they failed the MIS over the phone, they were administered the Modified Telephone Interview for Cognitive Status [TICS-M] test. "If they scored 31 or less on TICS-M, they were advised to seek a medical work-up." Dr. Abner explained. "Although the records were forwarded to us, we were still blinded to treatment status."
The main outcome of interest was clinical impairment, which was defined as impaired cognition indicated by failing scores on the CERAD or the TICS-M. Confirmed impairment was verified by a medical work-up, while suspected impairment was defined as that not yet confirmed. Subjective memory complaints were defined as self-perceived changes in memory that may not be reflected by cognitive testing. "Subjective memory complaints are common in older adults and have been previously reported to predict future cognitive decline," Dr. Abner noted. "All PREADVISE participants were asked at baseline if they had noticed any changes in their memory. Positive responders were also asked if they thought they had more problems with their memory than most people." Thus, participants were classified as having no memory complaint, memory changes, or memory problems at baseline.
The researchers used a stepwise Cox proportional hazards model to identify risk factors associated with the time from baseline to clinical impairment. The predictive variables in the model were both fixed and time dependent. Fixed variables (self-reported) were baseline age, education, black race, Hispanic ethnicity, mother’s age at childbirth, a family history of dementia, and comorbidities. Time-dependent variables were depression, anxiety, alcohol abuse, a high cholesterol level, antihypertensive use, hyperglycemia, thyroid disorder, and sleep apnea.
The mean age of the 3,701 participants was 68 years old, and most (77%) had no memory complaints at baseline. Participants underwent an average of eight annual assessments. Hypertension emerged as the most common comorbidity (34%), with 22% reporting the use of a statin. High cholesterol was the most common time-dependent comorbidity (68%), followed by antihypertensive use (64%), sleep apnea (18%), and depression (11%).
Dr. Abner reported that of the 3,701 men screened to date, 436 (12%) have clinical impairments with 332 having suspected mild cognitive impairment (MCI), 85 confirmed MCI, 4 suspected dementia, and 15 confirmed dementia. The risk of a clinical impairment was significantly increased by an older age at baseline (HR, 1.12 for every 1-year increment); baseline hypertension (HR, 1.96); African American race (HR, 3.24); a high school education or less (HR, 1.66); a history of diabetes (HR, 1.37); and, in the absence of apolipoprotein E4 (apo E4), baseline memory complaint (HR, 1.66 for changes vs. no complaint and HR, 4.48 for problems vs. no complaint). "It turns out that in the absence of apo E4, subjective memory complaints are predictive of clinical impairment," she said. "When apo E4 is present, the hazard ratios are not significant."