Abstract

Decline in cognitive function is an early symptom of dementia. Studies conducted in elderly women and men suggested that higher levels of endogenous estradiol and testosterone are associated with better cognitive function. However, recent studies in women demonstrated adverse effects of estrogen on cognition. To determine whether low levels of endogenous sex hormones are associated with increased risk of cognitive decline in very old men. The Frail Old Men Study is a population based prospective cohort study among 403 independently living elderly men in The Netherlands to determine risk factors of health and aging in the oldest old. Participants were aged 73–94 years at baseline in 1996 and were re–examined in 2000. At baseline, serum concentrations of total and free testosterone, total and free estradiol, estrone, and relevant covariates were determined. As a measure of global cognitive functioning, participants underwent the Mini Mental State Examination (MMSE) at baseline and follow–up after 4 years. Cognitive decline was defined as a decline of 4 or more points on the MMSE at follow–up. Follow–up was complete in 244 men. Of these, the mean (SD) baseline age was 77.4 (3.2), and the mean (range) baseline MMSE was 27.5 (20–30). At follow–up, 44 men (18%) had a decline of 4 or more points on the MMSE. Using multiple logistic regression analyses, levels of total and free testosterone were not associated with cognitive decline (OR per SD increase 1.1; 95%CI 0.8–1.5 and 1.0; 95%CI 0.7–1.4, respectively). Higher levels of total and free estradiol were related to increased risk of cognitive decline (OR per SD increase 1.5; 95%CI 1.0–2.1 and 1.4; 95%CI 1.0–2.0, respectively). For estrone the OR per SD increase was 1.4 (95%CI 1.0–2.0). These associations were independent of age, education, ApoE4, BMI, waist–to–hip ratio, blood pressure, diabetes, smoking, and serum cholesterol levels. The results do not support the hypotheses that high levels of endogenous sex hormones in elderly men are associated with lower risk of cognitive decline. Further longitudinal investigations are needed to more fully understand the role of hormonal effects on cognitive decline and dementia in older men.

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