Free testosterone and risk for Alzheimer disease in older men

Moffat, Scott D.; Zonderman, Alan B.; Metter, E. Jeffrey; Kawas, Claudia H.; Blackman, Marc R.; Harman, S. Mitchell; Resnick, Susan M.

doi:10.1212/wnl.62.2.188

Cited by 346 publications

(249 citation statements)

References 48 publications

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“…At the same time, APOE4 allele, which is a major risk of late onset AD, is associated with significantly lower level of circulating testosterone [88]. In accordance with these results, the Baltimore Longitudinal Study on Aging had detected significantly lower testosterone level 5-10 years in healthy men prior to their development of clinically manifest AD compared to those who did not develop AD [89].…”

Section: Androgens and Alzheimer's Diseasesupporting

confidence: 55%

Sex Hormones and Alzheimer’s Disease

Bahnasy¹,

El-Heneedy²,

El-Seidy³

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Alzheimer's disease (AD) is the most common type of dementia and the most common neurodegenerative disorder of elderly. It is not an accelerated form of aging but it is characterized by distinct temporospatial brain pathological changes, including amyloid plaques accumulation, neurofibrillary tangles deposition, synaptic loss and neuronal death with gross brain atrophy. These changes result in persistent progressive memory and cognitive decline interfering with the usual daily activities. AD is a multifactorial disorder results from the interaction of genetic, epigenetic, environmental and lifestyle factors. Estrogen, progesterone and androgen effects are important building stones in AD pathogenesis, and their effect in brain modulation and development results in different gender susceptibility to the disease. These sex hormones whether gonadal or neurosteroids (synthesized locally in the brain) play important neuroprotective roles influencing the individual's vulnerability to AD development, rate of mild cognitive impairment (MCI)/AD conversion and speed of AD progression. Despite the little therapeutic implications of hormonal replacement therapy in AD treatment, yet this topic still represents a challenging hopeful way to construct a strategy for the development of personalized, gender-specific AD management.

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Section: Androgens and Alzheimer's Diseasesupporting

confidence: 55%

Sex Hormones and Alzheimer’s Disease

Bahnasy¹,

El-Heneedy²,

El-Seidy³

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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“…26 Men with Alzheimer's disease had a lower ratio of total testosterone to SHBG compared with age-matched controls, 27 and a higher ratio of total testosterone to SHBG predicted reduced incidence of Alzheimer's disease in a longitudinal study of men aged 32-87 years at baseline. 28 However, one cross-sectional study did not show a relationship between total or free testosterone and measures of working memory, speed/attention or spatial relations in men aged from 48 to 80 years. 29 Contradictory findings have also been reported from other cross-sectional analyses of similarly aged men, including associations between lower free testosterone levels and higher performance on spatial visualization tasks, and between higher free and total testosterone levels and poorer verbal memory and executive performance but faster processing speed.…”

Section: Testosterone and Cognitive Function In Older Menmentioning

confidence: 95%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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“…26 Prospective studies of male volunteers in the Baltimore Longitudinal Study of Aging demonstrate that men showing greater rates of decline in testosterone over a 10-to 20-year period also show the greatest rates of cognitive declines, the lowest rates of glucose metabolism in brain regions subserving cognition and the greatest risk of Alzheimer's disease. [27][28][29] Serum levels of testosterone are reported to be lower in men with Alzheimer's disease compared to the controls, 30 and men with a neuropathological diagnosis for Alzheimer's disease have lower brain levels of testosterone. 11 Findings from randomized, placebocontrolled clinical trials of testosterone supplementation in older or hypogonadal men show variable cognitive effects.…”

Section: Evidence For Cognitive Effects Of Testosteronementioning

confidence: 99%

Cognitive changes associated with ADT: a review of the literature

Jamadar¹,

Winters²,

Maki³

2012

Asian J Androl

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The use of androgen deprivation therapy (ADT) has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen (PSA) test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. Most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomized study, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.

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Free testosterone and risk for Alzheimer disease in older men

Cited by 346 publications

References 48 publications

Sex Hormones and Alzheimer’s Disease

Sex Hormones and Alzheimer’s Disease

Are declining testosterone levels a major risk factor for ill-health in aging men?

Cognitive changes associated with ADT: a review of the literature

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