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Population aging is accompanied by an increase in cases of dementia, particularly Alzheimer's disease (AD). The aging process is accompanied by a spontaneous decline in the production of sex hormones. Circulating testosterone is predominantly (50-60%) through a strong link with the protein carriers of sex hormones (SHBG).
The testosterone seems to develop a neuroprotective role in the development of Alzheimer's disease.
The relationship between sex hormones and cognition, however, remains uncertain, where some studies have shown no correlation, such the investigation by Pennanen et al.8 which demonstrated high levels of testosterone in AD individuals. To compare levels of testosterone among individuals with mild or moderate Alzheimer's disease and individuals without dementia. A total of 41 men aged more than sixty years with AD were selected from the Reference Center for Cognitive Disorders (CEREDIC) and the Department of Neurology, both part of the Hospital of the University Medical School of Sao Paulo.
There were 31 men aged more than sixty years, without dementia, accompanied by the Multidisciplinary Assistance Clinic for the Aged (GAMIA) under the Geriatrics Division of the Clinicas Hospital of University of Sao Paulo. The groups were grouped according to criteria of the Clinical Dementia Rating9 (CDR) into Controls (Group I) formed by individuals without dementia (CDR-0), or patients (Group 2) with mild (CDR-1) or moderate AD (CDR-2).
The socio-demographic variables analyzed were age, education, marital status, occupation, religion and clinical profile of individuals: smoking, drinking, body mass index (BMI), history of cancer, coronary artery disease, diabetes mellitus, hypertension, heart failure, stroke, hyperthyroidism, hypothyroidism, benign prostatic hyperplasia, osteoporosis, auditory and visual acuity complaints and current medications.
The study was approved by the Ethics Committee of the Medical Hospital of the Faculty of Medicine of the University of Sao Paulo. At the end of this study all subjects had received a letter at their residences containing their cognitive performance and results of hormone examinations. Blood sample were collected within a period of fifteen days before or after the clinical evaluation, always in the morning, because of circadian fluctuations of testosterone.
Serum levels of total testosterone were evaluated by the Fluoroimmunoassay method (AutoDELFIA Wallace, Turku, Finland) while levels of SHBG were ascertained using the method immunofluorometric method (AutoDELFIA Wallace, Turku, Finland). The correlation between age and free testosterone was not statistically significant (p=0.068), but suggested that the higher the age, the lower the serum level of free testosterone (Table 3). The results of this cross-sectional study showed no difference in levels of testosterone among patients with Alzheimer's disease (mild or moderate) and the group without dementia. Few studies have investigated the relationship between testosterone and neurodegenerative diseases such as Alzheimer's disease while results to date have been contradictory. Moreover, Pennanen et al.8 performed a cross-sectional study comparing the testosterone levels in fourteen men with AD and sixteen men without dementia.
Because of the scarcity of studies in the medical literature on this topic it was difficult to deepen the discussion, highlighting the need for further studies that address the correlations between hormones and cognition.
In view of the limitations of this study outlined future studies are warranted that include assessments of bioavailable testosterone and groups which are matched for age.
Acknowledgments - The authors acknowledge the collaboration of all patients who took part in this study as well as the Departments of Geriatrics, Neurology and Laboratory of the Central Hospital of the Faculty of Medicine of the University of Sao Paulo. Objectives: To compare testosterone levels between older men with and without Alzheimer's disease.
Objetivos: comparar niveis de testosterona entre homens idosos com doenca de Alzheimer e sem demencia.


The prevalence of dementia doubles every 5 years after 65 years of age, reaching 15 to 20% after the 75th year.1 There are many studies have been conducted to unravel the pathological mechanisms, risk factors, protective factors and pharmacological agents able to halt or modify the course of AD. In elderly men the production of testosterone gradually falls.2,3 Many older men have testosterone levels at the lower limit of normal.
The receptors of androgen and estrogen are found in high concentrations in male sexual organs and in some other areas of the body including the brain, skeletal muscle, heart, vascular smooth muscle and bone.
Approximately 1 to 2% of circulating testosterone is free and 40 to 50% is weakly bound to albumin.3 The concentrations of free and albumin-bound testosterone represent the testosterone biologically available to the body. Studies suggest that testosterone inhibits hyperphosphorylation of tau protein and formation of amyloid-? This prospective study investigated the relationship between reduced levels of total testosterone and free testosterone index associated with age and subsequent development of Alzheimer's disease.
The result of free testosterone was based on the calculation of total testosterone and SHBG described by Vermeulen. Quantitative variables were analyzed by Student's t test or the non-parametric Kruskal-Wallis test. The AD group presented a trend toward lower levels of free testosterone and higher levels of SHBG. Since the AD group was older than the control group, it is possible that the observed trend of correlation between testosterone and AD was mediated by the age factor. It seems that biological function introduces bioavailable testosterone in the body and therefore a fraction of testosterone was not examined in this study that could have acted on cognitive function. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Methods: Fourteen men with Alzheimer's disease were compared with twenty eight men without dementia. Metodos: Comparamos 14 individuos com doenca de Alzheimer leve e moderada, provavel e possivel e 28 sem demencia. Currently, one of the aspects under study is the correlation between cognitive disorders and sex hormones in the elderly. The individuals were subjected to physical, neurological and neuropsychological evaluations every two years. The examinations were conducted at the Central Laboratory of the Hospital of the Faculty of Medicine of the University of Sao Paulo. Therefore, the assessment of levels of testosterone in the groups suggests that the variable was an age bias. His group cross developed a case-control study which evaluated 83 patients with AD and 103 patients without cognitive disorder. This study concluded that patients with AD showed high levels of total testosterone, free testosterone index and free androgen (free androgen index). All the patients in question had a diagnosis of AD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
Lopes et al10 found a positive correlation between hearing impairment and mild cognitive impairment in elderly patients through a cross case-control study. Within fifteen days before or after the described evaluation, measures of total testosterone and Sex Hormone Binding Globulin (SHBG) were performed.


Em um periodo de quinze dias antes ou depois da avaliacao clinica, foram realizadas coletas sericas de testosterona total e SHBG. It was concluded that the levels of free testosterone at initial assessment and at last hormone measurement showed an association with AD. This study includes patients with probable and possible AD, according to the NINCDS-ADRDA criteria (Working Group of the National Institute of Neurology and the Association of Alzheimer's disease and Related Disorders USA).
The group of patients with cognitive disorders was older than the control group and this difference was statistically significant where age was also found to be a bias factor in the cited study. This study showed low levels of total testosterone in elderly men with Alzheimer's disease. Thus, many trials have encountered the same difficulty in assessing elderly people with cognitive disorder, who are usually very old.
In contrast, among women there was no difference in levels of total testosterone between AD and controls. Quantitative variables were analyzed using Student's t test or Kruskal-Wallis test, while qualitative variables were analyzed using chi-square or Fisher test.
Variaveis quantitativas foram analisadas pelo teste T-Student (parametricas) ou Kruskal-Wallis (nao-parametricas); variaveis qualitativas, pelo teste Qui-quadrado ou de Fisher.
Suravarapu et al.12 showed a higher incidence of dementia in patients with lower levels of total and bioavailable testosterone, although the results were not statistically significant. Resultados: Medias de idade nos grupos Controle e DA foram 72,0 (±4,8) e 79,3 (±5,9) anos, respectivamente (p=0,001). Perhaps the main limitation of this study was that 36.7% of the original sample was composed of young people between 60-69 years. The short length of follow-up was another limiting factor leading to a small number of diagnosed dementia cases.
There were no statistically significant differences between the two groups for testosterone levels, although a trend was observed for the Alzheimer's disease group to present lower levels than the control group (p=0.066).
Nao houve diferenca estatisticamente significativa entre os niveis de testosterona livre nos dois grupos, embora se observasse uma tendencia do grupo DA a apresentar niveis menores que o controle (p=0,066). There was no direct correlation between free testosterone and age, although a trend was evident (p=0.068). Nao houve correlacao direta entre testosterona livre e idade, embora seja possivel observar uma tendencia (p=0,068). Conclusions: There was no significant difference in testosterone between men with AD and those without dementia.
Conclusoes: nao houve diferenca significativa quanto aos niveis de testosterona entre individuos com DA e sem demencia.



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