Longitudinal Assessment of Serum Free Testosterone Concentration Predicts Memory Performance and Cognitive Status in Elderly Men

Abstract

Circulating testosterone (T) levels have behavioral and neurological effects in both human and nonhuman species. Both T concentrations and neuropsychological function decrease substantially with age in men. The purpose of this prospective, longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

“…There was an overall pattern of associations between higher total T levels and smaller total GM volume but these associations were not statistically significant. Cognitive functioning was not related to SHBG or T levels, which is consistent with several studies in older adults (Lessov‐Schlaggar et al., 2005; Moffat et al., 2002; Yaffe et al., 2002). …”

“…Studies in men have focused predominantly on older age. It is well‐established that T levels decrease with age; and, this aging‐driven decline in total‐T or bio‐T levels has been associated with increased risk of dementia, cognitive decline (Holland et al., 2011; Moffat et al., 2002; Verdile et al., 2014; Yaffe, Lui, Zmuda, & Cauley, 2002), and dementia‐related neuropathology (Strozyk et al., 2007; Verdile et al., 2014). Increasing SHBG levels during aging have also been linked to cognitive disorders (Caldwell & Jirikowski, 2009; Muller, Schupf, Manly, Mayeux, & Luchsinger, 2010).…”

Can endocrine disruptors influence neuroplasticity in the aging brain?

“…In healthy men, the decline is gradual; by their seventies, their testosterone levels are about 40% below those found in men in their twenties. Although not wholly unambiguous, the literature largely supports the view that lower testosterone in older men is correlated with lower cognitive performance on tests of verbal and spatial memory (Moffat et al, 2002;Janowsky, 2006a,b). Figure 2 is based on Yaffe et al (2002), who found that free, rather than total testosterone, correlated with performance in a sample of older men (mean of 73 yrs old).…”

A view of geriatrics through hormones. What is the relation between andropause and well-known geriatric syndromes?

“…Animal and human studies support a positive effect of T on global cognitive function [8,20] and separate cognitive domains such as memory [59][60][61], attention [60], visuospatial ability [59,61,62] and executive function [63]. Visuospatial function seems particularly related to androgen status [62].…”