Stephan Bandelow

Testosterone levels and cognition in elderly men: A review

Average testosterone levels and many cognitive functions show a decline with age. There is evidence to suggest that this association is not just age related. Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function. Alzheimers disease (AD) is characterised by brain pathology affecting cognitive function and AD prevalence increases with age. Testosterone levels are lower in AD cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede AD onset. Men with AD may show accelerated endocrinological ageing, characterised by an earlier lowering of thyroid stimulating hormone, an earlier increase in sex hormone binding globulin (SHBG), a subsequent earlier decrease in FT and an earlier increase in gonadotropin levels in response to this. Positive associations have been found between testosterone levels and global cognition, memory, executive functions and spatial performance in observational studies. However, non-significant associations were also reported. It may be that an optimal level of testosterone exists at which some cognitive functions are improved. This may be modified with an older age, with a shifting of the optimal testosterone curve to maintain cognition to the left and a lower optimal level thus needed to be beneficial for the brain. Genetic factors, such as APOE and CAG polymorphisms may further interact with testosterone levels in their effects on cognition. The roles of SHBG, gonadotropins, thyroid hormones and estrogens in maintaining cognitive function and preventing dementia in men are also not completely understood and should be investigated further. Hypogonadal men do not seem to benefit from testosterone supplementation but small scale, short term intervention studies in eugonadal men with and without cognitive impairments have shown promising results. Larger randomised, controlled trials are needed to further investigate testosterone treatment in protecting against cognitive decline and/or dementia.

Caffeine Improves Physical and Cognitive Performance during Exhaustive Exercise

UNLABELLED Caffeine is thought to act as a central stimulant and to have effects on physical, cognitive, and psychomotor functioning. PURPOSE To examine the effects of ingesting a performance bar, containing caffeine, before and during cycling exercise on physical and cognitive performance. METHODS Twenty-four well-trained cyclists consumed the products [a performance bar containing 45 g of carbohydrate and 100 mg of caffeine (CAF), an isocaloric noncaffeine performance bar (CHO), or 300 mL of placebo beverage (BEV)] immediately before performing a 2.5-h exercise at 60% VO2max followed by a time to exhaustion trial (T2EX) at 75% VO2max. Additional products were taken after 55 and 115 min of exercise. Cognitive function measures (computerized Stroop and Rapid Visual Information Processing tests) were performed before exercise and while cycling after 70 and 140 min of exercise and again 5 min after completing the T2EX ride. RESULTS Participants were significantly faster after CAF when compared with CHO on both the computerized complex information processing tests, particularly after 140 min and after the T2EX ride (P < 0.001). On the BEV trial, performance was significantly slower than after both other treatments (P < 0.0001). There were no speed-accuracy tradeoffs (P > 0.10). T2EX was longer after CAF consumption compared with both CHO and BEV trials (P < 0.05), and T2EX was longer after CHO than after BEV (P < 0.05). No differences were found in the ratings of perceived exertion, mean heart rate, and relative exercise intensity (% VO2max; P > 0.05). CONCLUSION Caffeine in a performance bar can significantly improve endurance performance and complex cognitive ability during and after exercise. These effects may be salient for sports performance in which concentration plays a major role.

Visual Impairment in Alzheimer's Disease: A Critical Review

Visual impairment is a common symptom of Alzheimers disease (AD). Recent studies have demonstrated the potential of visual interventions to improve the functioning of AD patients. Therefore, clarification of the profile of visual deficits in AD and possible mechanisms underlying these deficits are needed. This review focuses on three areas as mechanisms for the visual impairment in AD: 1) the broad-band pathway deficit; 2) glaucoma; and 3) the relative dysfunction of the ventral and dorsal streams of vision. While much research has been produced with regard to these areas, methodological flaws and lack of continuity between studies has led to conflicting findings. Nevertheless, recent imaging research suggests that the loss of retinal ganglion cells in AD may play an important role in the visual deficit in AD. This review looks to critically evaluate current research and highlight the need to investigate recent significant findings in primary vision research in understanding the impairment of vision in AD.

Breakfast consumption and cognitive function in adolescent schoolchildren

This study examined the effects of breakfast consumption on cognitive function, mood and blood glucose concentration in adolescent schoolchildren. With the institutions ethical advisory committee approval, 96 adolescents (12 to 15 years old) completed two randomly assigned trials (one following breakfast consumption and one following breakfast omission), scheduled 7 days apart. Cognitive function tests (visual search test, Stroop test and Sternberg paradigm), a mood questionnaire and a finger prick blood sample (in a subgroup of 60 participants) were completed immediately following breakfast and 120 min after the baseline measures. Following breakfast consumption, accuracy on the more complex level of the visual search test was higher than following breakfast omission (p=0.021). Similarly, accuracy on the Stroop test was better maintained across the morning following breakfast consumption when compared to breakfast omission (p=0.022). Furthermore, responses on the Sternberg paradigm were quicker later in the morning following breakfast consumption, particularly on the more complex levels (p=0.012). Breakfast consumption also produced higher self-report energy and fullness, lower self-report tiredness and hunger and higher blood glucose concentrations (all p<0.0005). Overall, the findings of the present study suggest that breakfast consumption enhances cognitive function in an adolescent population when compared to breakfast omission.

Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review.

Low testosterone (T) levels may predispose to Alzheimer disease (AD), but it is unclear whether this is a co-morbid effect due to cachexia, subclinical hyperthyroidism or other co-morbidity. The biological plausibility for potential protective effects of T on brain functions is substantial. In addition, higher levels of gonadotropins found in older cases with AD suggest that low levels of T are not due to brain degeneration and that the hypothalamic-pituitary-gonadal (HPG) axis is still intact. Men genetically at risk for AD were also already found to have lower levels of T. However, despite having lower levels of T, women do not show accelerated cognitive decline with age when compared to men. In addition, castration has not necessarily shown a decline in cognitive functions; some studies even found improvement of memory recall. Age may be an important factor when assessing optimal levels of T and several studies suggest that free or bioavailable T may be a better marker than total T levels when investigating associations of androgen activity with cognitive function. Small-scale T intervention trials in elderly men with and without dementia suggest that some cognitive deficits may be reversed, at least in part, by short term T supplementation. Age and prior hypogonadism may play an important role in therapy success and these factors should be investigated in more detail in future large scale randomized controlled studies. For elderly women, T treatment does not seem to have additional benefits over estrogen treatment for postmenopausal complaints and cognitive decline and may increase cardiovascular disease.

Modification of estrogen's association with Alzheimer's disease risk by genetic polymorphisms.

Contrasting effects of estrogen treatment on cognitive function and Alzheimers disease (AD) risk have been reported. It may be that genetic factors modify these relations. In the present study, 696 participants from the Oxford Project to Investigate Memory and Ageing were included (355 AD cases, 341 controls). Those individuals with other types of dementia and those using hormone treatment had been excluded. Analyses controlled for body mass index, age at blood sampling, and education. Analyses of variance revealed main effects, but not an interaction, for apolipoprotein E (APOE) and Catechol-O-methyl transferase (COMT) genotypes on estradiol (E2) levels in men (p=0.003 and p=0.10, respectively), but not in women (p=0.82 and p=0.49, respectively). Men carrying the APOE ε4 allele had lower E2 levels, while those carrying the COMT Val/Val alleles had higher E2 levels compared to Met/Val (p<0.05) allele carriers. Higher estrone (E1) levels and carrying the APOE ε4 allele (but not COMT alone, or in combination with the APOE genotype) were independent risk factors for AD. Similar to earlier studies, the heterozygous COMT genotype (Met/Val) showed a synergistic effect with the APOE ε4 allele being non-significantly associated with lower cognitive function. In conclusion, the present study suggests that elevated E1 levels significantly increase AD risk in both men and women. However, interactions between APOE ε4 and genetic polymorphisms related to sex steroid metabolism and AD risk need to be further investigated.

Should surgical menopausal women be treated with estrogens to decrease the risk of dementia

Hormone treatment to improve or maintain cognitive function in postmenopausal women has always been a contentious issue. In the late 1980s and 1990s, there was brief enthusiasm for hormones to be a potential prophylactic treatment for dementia, based on findings from cell culture, animal, small treatment, and observational studies.1 However, the tide turned when a large randomized placebo-controlled study (the Womens Health Initiative Memory Study or WHIMS) found an increased risk for dementia already after 1 year of combination hormone treatment in women over 65 years of age.1,2 This study also confirmed earlier reported increased risks with long-term hormone treatment for dangerous adverse events, such as cardiovascular disease, stroke, and breast cancer.2 The use of hormone treatment dropped by a third and NIH guidelines2 recommended that hormones, when indicated for severe perimenopausal symptoms, should be prescribed at the lowest dose for the shortest period possible to reduce these risks. So how long should surgically menopausal women, who often report severe menopausal symptoms, be treated? In this issue of Neurology ®, the Mayo Clinic team in Minnesota reports that surgical menopause overall increased the risk of dementia or cognitive impairment by 45% in a large observational follow-up study.3 When unilateral oophorectomy was performed before 41 years of age, there was an almost doubled risk and when it was done before 34 years of age, this risk was more than four times higher. For …

Prevalence of Behavioural and Psychological Symptoms of Dementia in Individuals with Learning Disabilities.

A review of 23 studies investigating the prevalence of Behavioural and psychological symptoms of dementia (BPSD) in the general and learning disability population and measures used to assess BPSD was carried out. BPSD are non-cognitive symptoms, which constitute as a major component of dementia regardless of its subtype Research has indicated that there is a high prevalence of BPSD in the general dementia population. There are limited studies, which investigate the prevalence of BPSD within individuals who have learning disabilities and dementia. Findings suggest BPSDs are present within individuals with learning disabilities and dementia. Future research should use updated tools for investigating the prevalence of BPSD within individuals with learning disabilities and dementia.

Meta-analyses of the effect of hormone treatment on cognitive function in postmenopausal women.

As we age, most of us experience a certain degree of cognitive decline. In most cases, this decline is gradual. However, in some cases, cognitive impairment is so severe that it can be classified as dementia and this impacts greatly on activities of daily living. Alzheimers disease, the most common form of dementia, has been linked to the reduction in estrogen levels that comes with aging. More specifically, many researchers have hypothesized that estrogen, and hence estrogen replacement via hormone therapy, could protect against cognitive decline in women. However, recent randomized, controlled trials did not reflect this. In fact, some reports showed that hormone therapy could have detrimental effects on cognitive function in older postmenopausal women. The most publicized of these has been the Womens Health Initiative Memory Study. Studies have thus yielded conflicting results and conclusions. The reasons for this may be due to a number of factors, such as the age of participants, the time of hormone therapy onset (‘window of opportunity’ theory), type of treatment, type of menopause (surgical or natural) and, possibly, genetic risk factors. We performed quantitative and qualitative meta-analyses and reviewed each of these factors in detail. The future may lie in combining these factors in order to fully understand the potential mechanisms behind estrogen and its effect on cognition.

Associations Between Sedentary Behaviors and Cognitive Function: Cross-Sectional and Prospective Findings From the UK Biobank

We investigated the cross-sectional and prospective associations between different sedentary behaviors and cognitive function in a large sample of adults with data stored in the UK Biobank. Baseline data were available for 502,643 participants (2006-2010, United Kingdom). Cognitive tests included prospective memory (baseline only: n = 171,585), visual-spatial memory (round 1: n = 483,832; round 2: n = 482,762), fluid intelligence (n = 165,492), and short-term numeric memory (n = 50,370). After a mean period of 5.3 years, participants (numbering from 12,091 to 114,373, depending on the test) also provided follow-up cognitive data. Sedentary behaviors (television viewing, driving, and nonoccupational computer-use time) were measured at baseline. At baseline, both television viewing and driving time were inversely associated with cognitive function across all outcomes (e.g., for each additional hour spent watching television, the total number of correct answers in the fluid intelligence test was 0.15 (99% confidence interval: 0.14, 0.16) lower. Computer-use time was positively associated with cognitive function across all outcomes. Both television viewing and driving time at baseline were positively associated with the odds of having cognitive decline at follow-up across most outcomes. Conversely, computer-use time at baseline was inversely associated with the odds of having cognitive decline at follow-up across most outcomes. This study supports health policies designed to reduce television viewing and driving in adults.