Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study.
ABSTRACT Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.
Community-based, cross-sectional study of 3369 men aged 40-79 years.
Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE(2)) and 5alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE(2) were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.
Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 micromol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.
Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.
Article: The neuropsychology of aging.[show abstract] [hide abstract]
ABSTRACT: There are three general categories of causes of the cognitive decline associated with aging: disuse, disease, and aging per se. People tend to use certain skills or abilities less with age and, thus, those skills decline due to the disuse. Physical illnesses tend to increase with age, which will tend to compromise cognitive functioning. Further, there are actual neurobiological changes with age that will contribute to deterioration of cognitive abilities. Variability of performance between different individuals within an age group increases with age due to each of these three major contributing factors to age decline. The best defense against age-related cognitive deterioration is practice. Practice tends to mitigate the effects of aging by not allowing disuse to occur. In addition, practice can overcompensate for age effects by building a larger reserve capacity to offset any real neurobiological effects of age. Practice can also lead to compensatory strategies in which alternative way of maintaining performance levels are found.Experimental Gerontology 01/1995; 30(3-4):431-42. · 3.91 Impact Factor
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ABSTRACT: To determine whether low plasma dehydroepiandrosterone sulfate (DHEAS) levels predict poor cognitive function in the elderly. A prospective, population-based study with periodic clinical evaluations and 100% follow-up for vital status. Rancho Bernardo, California 270 men and 167 women (80% of surviving, local, age-eligible subjects) from the Rancho Bernardo cohort who had plasma obtained for DHEAS assays in 1972 to 1974 and screening for dementia in 1988 to 1991. DHEAS levels were measured by radioimmunoassay. There were five interviewer-administered standard screening tests of cognitive function: Mini-Mental Status Examination, Buschke selective reminding test, Trails B, category fluency, and Heaton Visual Reproduction test. DHEAS levels were higher in men than women and decreased with age in both sexes. There were no significant differences in age-adjusted DHEAS levels in the percent of men or women with categorically impaired performance on any test. When analyzed as a continuous variable, DHEAS levels were significantly correlated with only one test, the Bushke, and only in women. Low baseline DHEAS levels were not associated with any mention of dementia on death certificates or with non-participation of survivors. Low levels of DHEAS predicted mortality in men more than in women such that men were more likely to have died before cognitive function testing than women. The single DHEAS-memory association, restricted to women, is most likely to be spurious, consequent to multiple comparisons. We cannot exclude a true effect of low DHEAS, restricted to women and reflecting their better survival than men.Journal of the American Geriatrics Society 05/1994; 42(4):420-3. · 3.98 Impact Factor
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ABSTRACT: The molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human androgen receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon. An inverse relationship was observed between CAG repeat length and AR mRNA and protein levels. Trinucleotide repeat lengths of 43 and 65 associated with spinal/bulbar muscular atrophy decreased AR mRNA and protein levels but did not alter equilibrium binding affinity for [3H]R1881 or inherent transcriptional activity of AR, expressed as androgen-dependent fold induction of a mouse mammary tumor virus promoter-luciferase reporter vector. The findings indicate that glutamine expansion up to 66 residues in the NH2-terminal domain of AR does not alter AR functional activity. Rather, CAG repeat expansion in the region of the first exon reduces AR mRNA and protein expression. The study reveals a previously unrecognized effect of CAG repeat length on AR mRNA expression and a novel molecular mechanism for androgen resistance.Molecular Endocrinology 01/1997; 10(12):1527-35. · 4.75 Impact Factor