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THE ROLE OF TESTOSTERONE ON COGNITION AND BETA AMYLOID LEVELS
IN THE AGEING MALE
Martins, R.N.
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private
Hospital, Edith Cowan University and University of
Western Australia
Alzheimer's disease is the most common neurodegenerative disorder
in the developed world. Ageing and the e4 allele of
apolipoprotein are considered to be the major risk
factors for Alzheimer's disease, but the actual trigger
has still remained elusive. What is known is that
a small peptide beta amyloid is central to the pathogenesis
of Alzheimer's disease. We have demonstrated that
depletion of testosterone in men with prostate cancer
results in increased levels of plasma beta amyloid.
We have reproduced and extended these findings in
castrated guinea pigs where beta amyloid levels are
also observed in the brain. In a pilot study of cognitively
normal individuals and mild to moderate AD cases we
observed that an increase in testosterone levels correlated
negatively with plasma beta amyloid levels. We have
recently examined the relationship between the genetic
risk for Alzheimer's disease (i.e. possession of an
e4 allele) and serum androgen levels on cognitive
functioning in a cross-sectional study with 67 males
aged between 55 to 85 years. We observed that higher
androgen concentrations were associated with better
general cognitive performance in healthy elderly men
lacking the e4 allele. By contrast, in elderly men
carrying the e4 allele, higher androgen concentrations
were associated with lower scores on tests of executive
functioning and attention. These interesting findings
will be clinically important in determining which
individuals will benefit from hormone replacement
therapy but must await confirmation from larger independent
studies.
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