Testosterone levels and spatial ability in men

Testosterone (T) levels were measured by salivary assays in 59 males at times of the day when T was expected to be highest and lowest. Relationships were evaluated for mean hormone levels across the two sessions and hormone level changes between sessions with performance on three-dimensional mental rotations, a spatial test which customarily favours males. An anagrams task and the digit symbol test were used as controls. Mental rotations scores showed a significant positive relationship with mean T levels but not with changes in T. There were no significant relationships between control test scores and mean T levels. Findings are discussed in terms of their contributions to the resolution of ambiguities in prior reported data.     

Androgens in the etiology of Alzheimer's disease in aging men and possible therapeutic interventions

Animal experiments and cell biology studies have provided evidence that both estrogens and androgens can play a protective role against Alzheimer's disease (AD) related neurodegeneration. Males who become hypogonadal in later life often report problems with their memory. Lower than normal testosterone levels have also been detected in patients prior to the onset of AD, as well as in younger late-onset male AD patients, when compared to appropriate controls. The results of some small clinical trials suggest that testosterone can improve cognitive function in andropause. Although such improvement in cognitive function is subtle, patients on testosterone replacement therapy have reported memory improvements in both declarative and procedural domains. In contrast, there is no clinical evidence to date which suggest that the hormone dihydroepiandrosterone (DHEA) can improve cognitive function. Rises in the levels of the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been associated with AD, but the clinical effects of reducing their levels remain to be determined. We hypothesize that androgens, gonadotropin modulators, or perhaps selective androgen receptor modulators may be useful components of therapy aimed at preventing the onset or delaying the progression of AD in male patients.     

Testosterone and cognition in normal aging and Alzheimer's disease: an update

There is evidence to suggest that testosterone loss constitutes a risk for cognitive decline and possibly dementia, and that elderly men might benefit from exogenous supplementation of testosterone. Studies in non-human animals repeatedly report neuroexcitatory and neuroprotective properties of testosterone and enhanced memory performance after acute or chronic treatment. Positive effects of testosterone supplementation in older men have been reported in several, but not all, studies and require replication in larger randomized clinical trials before recommendations for clinical practice can be made. The current review summarizes recent studies on the neurobiological connection between testosterone and cognitive function in humans and non-human animals. When appropriate, we use the hippocampus as a model structure given it's involvement in sexually dymorphic spatial ability and sensitivity to both androgens and aging. In addition, a number of potential explanations of the discrepancy between data obtained in humans and non-human animals are discussed.     

Testosterone supplementation improves spatial and verbal memory in healthy older men.

OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition. METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests. RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures. CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.     

Testosterone deficiency and apathy in Parkinson's disease: a pilot study

BACKGROUND: Low testosterone in men with Parkinson's disease may be associated with non-motor symptoms of the disease, such as apathy. OBJECTIVE: To determine the association between free serum testosterone level and apathy in elderly men with Parkinson's disease. METHODS: Consecutive non-demented patients (n = 49) and knowledgeable informants (n = 40) participated in the study. Patients and informants reported on apathy using the Frontal Systems Behavior Scale and two visual analogue scales. Patients also provided self reported symptoms of depression on the Beck depression inventory-II. Blood samples were drawn at the time of assessment to determine testosterone levels. RESULTS: A low total testosterone concentration was found in 46.9% of the patients, defined as < or = 325 ng/dl. Free testosterone was significantly correlated with both patient reported and informant reported apathy, independent of disease severity. CONCLUSIONS: Apathy is common in Parkinson's disease and is inversely correlated with free testosterone. Testosterone replacement therapy could be considered as a potential treatment for apathy in some men with Parkinson's disease. More research is needed to replicate these findings and to investigate the response to treatment.     

Testosterone and hand skill in right-handed men and women

The relationship between serum testosterone level and hand skill was studied in right-handed young adults. Hand preferences was assessed by the Edinburgh Handedness Inventory. Hand skill was assessed by the peg moving task. Serum testosterone level was determined using tritium-marked-radioimmunoassay. In the total sample, only the right-hand skill showed a direct correlation and an inverse correlation with serum testosterone for men and women, respectively. In male subjects with right-eye preference, both hand skills exhibited a direct relation to serum testosterone. In the total sample, there was a direct and an inverse relationship between the difference in skill between hands and serum testosterone in men and women, respectively. This was, however, affected by right-eye and right-foot preference. It was concluded that the serum testosterone in young adults is associated with hand skill exhibiting fundamental differences between men and women; the left cerebral hemisphere seems to be the main target of testosterone.     

Testosterone and nonverbal intelligence in right-handed men and women

The relationship between serum testosterone level and nonverbal intelligence was studied in right-handed young adults. Hand preference was assessed by the Edinburgh Handedness Inventory. Serum testosterone level was determined using tritium-marked-radioimmunoassay. Only in men, nonverbal intelligence (Cattell's Culture Fair Intelligence Test) was found to be significantly and directly related to serum testosterone levels. It was concluded that the serum testosterone in young adults is associated with nonverbal intelligence exhibiting fundamental differences between men and women.     

Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications

Autophagy is a highly conserved intracellular pathway involved in the elimination of proteins and organelles by lysosomes. Known originally as an adaptive response to nutrient deprivation in mitotic cells, autophagy is now recognized as an arbiter of neuronal survival and death decisions in neurodegenerative diseases. Studies using postmortem human tissue, genetic and toxin-induced animal and cellular models indicate that many of the etiological factors associated with neurodegenerative disorders can perturb the autophagy process. Emerging data support the view that dysregulation of autophagy might play a critical role in the pathogenesis of neurodegenerative disorders. In this review, we highlight the pathophysiological roles of autophagy and its potential therapeutic implications in debilitating neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer's, Parkinson's and Huntington's diseases.     

Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men.

BACKGROUND: Testosterone (T) level declines progressively with age. Psychiatric symptoms of T deficiency (e.g., dysphoria, fatigue, irritability, low libido) are also symptoms of depression, and appear to be variably expressed. METHODS: We assessed independent measures of hypothalamic-pituitary-gonadal axis functioning, i.e., total T level and androgen receptor (AR) CAG repeat length (CAG RL), a genetic trait marker associated with AR function; and depression (diagnosed by above-threshold score on the Center for Epidemiologic Studies-Depression Scale [CES-D]) in 1000 men (mean age = 62.6 years; SD = 8.3) who participated in the Massachusetts Male Aging Study. RESULTS: There were 110 (11%) men with "depression" (CES-D score > or = 16) in the analysis sample. Neither total T level nor CAG RL was associated with depression in bivariate analyses. Among men with shorter CAG RLs, the percentage of men with depression was 21.6% in the lowest subgroup of total T (defined by quintiles) and 4.2% in the highest subgroup of total T. This was confirmed in simple logistic regression models with depression as the dependent variable and continuous total T as the predictor, run separately within the three CAG RL subgroups: depression was significantly and inversely associated with total T in men with shorter CAG RLs but not in men with moderate and longer CAG RLs. CONCLUSIONS: CAG isotype, a genetic trait marker of androgen receptor function, may mediate the expression of the central nervous system effects of T deficiency in men.     

Plasticity of neuroendocrine-immune interactions during aging.

Intact neuroendocrine-immune interactions are essential for the development and functional maintenance of both systems. Normal physiological aging appears to be, in part, dependent on age-related modifications of neuroendocrine-immune interactions. The thymus plays a major role in this context. Experimental manipulation at the thymic or neuroendocrine level may reciprocally correct the age-associated dysfunctions, suggesting the reversible nature of such phenomena.     

Psychoneuroendocrinoimmunology: the basis for a novel therapeutic approach in aging.

Along with the nervous and the endocrine systems, the immune system is one of the three major integrative systems in higher organisms. Growing evidence demonstrates an intimate relationship between the immune system and the endocrine and nervous systems: The psychoneuroendocrine system can influence the immune response and thereby the capacity of the organism to cope with illness, and the immune system can have an impact on neuroendocrine function. Such cross-talk among systems is dependent upon feedback loops working to maintain homeostatic equilibrium.     

No relationship between testosterone levels and depressive symptoms in aging men.

We investigated the associations between depression and serum testosterone levels in the elderly. There was no significant difference in the mean levels of the serum testosterone between the groups of patients and normals. For both groups, there was no significant correlation between testosterone and total depression scores or age.     

Insecure attachment and alexithymia in young men with mood symptoms

According to attachment theorists, affect regulation and quality of attachment are closely linked. As a personality trait associated with deficits in the cognitive processing and regulation of affects, alexithymia has been hypothesized to correlate with insecure attachment. To test this hypothesis, we studied the relationships between alexithymia, adult attachment style, and retrospective memories of separation anxiety symptoms during childhood in 100 young men with clinically significant mood symptoms. The most common DSM-IV diagnosis (N = 72) was adjustment disorder with depressed mood, with anxiety, or with mixed anxiety and depressed mood. Each participant completed the Twenty-Item Toronto Alexithymia Scale (TAS-20), the Beck Depression Inventory (BDI), the state form of the State-Trait Anxiety Index (STAI), the Attachment Style Questionnaire (ASQ), the Relationship Questionnaire (RQ), and the Separation Anxiety Symptom Inventory (SASI). Alexithymic traits were more pronounced in those participants who had patterns of insecure attachment and who reported more severe symptoms of separation anxiety during childhood, independently of the severity of their current anxiety and depressive symptoms. Among the subgroup of participants with insecure attachment styles, those with preoccupied or fearful patterns had a higher prevalence of alexithymia (65% and 73%, respectively) than those with a dismissing pattern (36%). These data suggest a role for early developmental factors in the etiology of alexithymia     

Testosterone therapy in men with Parkinson disease: results of the TEST-PD Study

BACKGROUND: Testosterone deficiency has been reported in patients with Parkinson disease (PD), Alzheimer disease, and Huntington disease. It is not known whether testosterone therapy (TT) in men with borderline hypogonadism and neurodegenerative diseases will be of substantial benefit. Previously, we reported that testosterone deficiency is more common in patients with PD compared with age-matched control subjects, and we also reported in 2 small open-label studies that some nonmotor symptoms responded favorably to TT. OBJECTIVE: To define the effects of TT on nonmotor and motor symptoms in men with PD and probable testosterone deficiency. DESIGN: Double-masked, placebo-controlled, parallel-group, single-center trial. PATIENTS: Two experimental groups: patients with PD who were receiving either TT or placebo. INTERVENTIONS: Participants received either the study drug by intramuscular injection (200 mg/mL of testosterone enanthate every 2 weeks for 8 weeks) or placebo (isotonic sodium chloride solution injections). In patients in each group, the testosterone serum concentration was obtained at each study visit. During 2 study visits, testosterone levels were blindly evaluated and the intramuscular testosterone dose was increased by 200 mg/mL if the free testosterone value failed to double from the baseline value. MAIN OUTCOME MEASURES: The primary outcome variable was the St Louis Testosterone Deficiency Questionnaire, and secondary outcome measures included measures of mood, cognition, fatigue, motor function, and frequency of adverse events. At the end of the double-blind phase, all patients were offered open-label TT and were followed up after 3 and 6 months. RESULTS: Fifteen patients in the placebo group (mean age, 69.9 years), receiving a mean total levodopa equivalent dose of 924 mg/d, had a baseline free testosterone level of 47.91 pg/mL, compared with 15 patients in the TT group (mean age, 66.7 years), receiving an average total levodopa equivalent dose of 734 mg/d, who had a baseline free testosterone level of 63.49 pg/mL. Testosterone was generally well tolerated. More subjects in the TT group experienced lower extremity edema (40% vs 20%). In 2 patients, 1 in each group, prostate-specific antigen levels were elevated from baseline. The improvement in the TT group compared with the placebo group (1.7 vs 1.1) on the St Louis Testosterone Deficiency Scale was not statistically significant. In addition, there were no significant differences in motor and nonmotor features of PD between the 2 groups, although a few subscales showed improvements (Hopkins Verbal Learning Test, P<.04; and Backward Visual Span subtrial, P<.03). However, long-term open-label TT resulted in delayed but sustained improvement in subjects in the TT group who continued to receive treatment (n = 6) compared with subjects in the placebo group who elected not to receive TT (n = 3). CONCLUSIONS: Testosterone therapy was generally well tolerated in elderly men with PD and probable testosterone deficiency. While there was no significant difference in the motor and nonmotor scales between the TT and placebo groups at the end of 8 weeks compared with baseline, this may be due to several study limitations, including small sample size, a strong placebo effect with intramuscular therapy, and short follow-up that did not allow measurement of delayed effects of TT in some subjects. Until more definitive studies are reported, practitioners should be particularly cautious in treatment of low testosterone concentrations in men with PD and borderline testosterone deficiency, and careful consideration should be given to the risks vs the benefits of TT.     

Neurocysticercosis: neurologic, pathogenic, diagnostic and therapeutic aspects

Worldwide neurocysticercosis is the most common parasitic infection of the human brain and meninges. Clinical features of the illness vary with the stage of ova infection, but most problems arise when the mature cyst degenerates. Seizures, increased intracranial pressure, and focal neurologic signs then often develop. Computed tomography and magnetic resonance usually demonstrate Cysticercus cellulosae cysts in the brain. A new immunoblot test for antibodies to the cysticercus seems both sensitive and specific. Treatment with praziquantel or albendazole has hastened the disappearance of the cysts on computed tomography and improved clinical symptoms.