Cognitive performance and structural brain correlates in long-term anabolic-androgenic steroid exposed and nonexposed weightlifters.

OBJECTIVE: To test for associations between long-term anabolic-androgenic steroid (AAS) use and cognitive functioning, and establish a candidate neuronal basis by assessing the associations between cognitive performance and brain morphology both in users and nonusers. METHOD: Eighty four previous or current AAS-users and 69 non-AAS-using male weightlifters aged 19-75 years (mean 32.6, SD 8.8) underwent MRI of the brain and a comprehensive neuropsychological test battery. Performance on fine motor speed, speed of processing, learning and memory, working memory, executive functioning, and problem solving was compared between the groups, and between AAS users with short versus long AAS exposure. Associations between cognitive scores and regional cortical thickness and arealization defined using FreeSurfer were tested using linear models. RESULTS: Relative to nonexposed, AAS-exposed weightlifters performed significantly worse on several cognitive domains, independent of age, education, verbal IQ, and exposure to classical drugs of abuse. Strongest effects were observed for speed of processing (ηp2 = .07), working memory (ηp2 = .08) and problem solving (ηp2 = .09). Longer duration of AAS-use was associated with poorer memory function (ηp2 = .11). Within AAS users, individuals with better memory and working memory performance had with thicker frontoparietal cortex and larger medial frontal surface area, respectively. CONCLUSIONS: Prolonged high-dose AAS use is associated with poorer cognitive function across multiple domains, and the observed regional associations between cortical brain morphometry and memory and working memory performance may suggest differential brain-based mechanisms. The public, health care professionals, and policymakers should be aware that use of AAS in large doses potentially could lead to poorer brain health and cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Types or modes of malingering? A confirmatory factor analysis of performance and symptom validity tests.

Recently, the dichotomy between performance validity tests (PVT) and symptom validity tests (SVT) has been suggested to differentiate between invalid performance and invalid self-report, respectively. PVTs are typically used to identify malingered cognitive impairment, while SVTs identify malingered psychological or somatic symptoms. It is assumed that people can malinger different types of problems, but the impact of modes of reporting invalidly has been largely unexplored. A mixed neurological sample (n = 130) was tested with the Test of Memory Malingering, the Forced Recognition part of the California Verbal Learning Test, and the self-report Structured Inventory of Malingered Symptoms (SIMS). Confirmatory factor analyses testing both method- and content-based factor models found best fit for the method-based division. Regression analyses of other self-rating and performance-based tests provided further support for the importance of type of methods used to collect information. While acknowledging the types of symptoms malingered, the clinician is advised also to consider how information is gathered by using both PVTs and SVTs. SIMS is a good candidate for a stand-alone SVT, although the utility of the Low Intelligence subscale is questionable as a validity measure.

Effects of cognitive training on gray matter volumes in memory clinic patients with subjective memory impairment.

Subjective memory impairment (SMI) is a common risk factor for Alzheimer's disease, with few established options for treatment. Here we investigate the effects of two months episodic memory training on regional brain atrophy in 19 memory clinic patients with SMI. We used a sensitive longitudinal magnetic resonance imaging protocol and compared the patients with 42 matched healthy volunteers randomly assigned to a group performing the same training, or a no-training control group. Following intervention, the SMI sample exhibited structural gray matter volume increases in brain regions encompassing the episodic memory network, with cortical volume expansion of comparable extent as healthy training participants. Further, we found significant hippocampal volume increases in the healthy training group but not in the SMI group. Still, individual differences in left hippocampal volume change in the patient group were related to verbal recall improvement following training. The present results reinforce earlier studies indicating intact brain plasticity in aging, and further suggest that training-related brain changes can be evident also in the earliest form of cognitive impairment.

Hippocampal subfield volumes correlate with memory training benefit in subjective memory impairment.

Although some older adults experiencing memory problems have been shown to benefit from cognitive training, evidence regarding who will improve from this type of intervention is lacking. Automated hippocampal volumetry might be used to foresee treatment outcomes. We hypothesized that larger hippocampal volumes are associated with greater memory performance changes following training, and that effects are selectively related to specific hippocampal subfields. 19 memory clinic outpatients with subjective memory impairment (mean age=60.9 years) underwent MRI-scanning and then followed an eight week training scheme aimed at improving verbal memory. We assessed verbal memory before and after training, and tested whether pretraining hippocampal volumes were related to memory improvements. To delineate regional specificity, we employed a new technique enabling automated volumetry of seven hippocampal subfields - including the cornu ammonis (CA) sectors and the dentate gyrus (DG). The results showed that larger hippocampal volumes before training were related to greater verbal recall improvements. Subfield volumetry revealed specific correlations between memory improvement and pretraining volumes of the left CA2/3 and CA4/DG. Depressive symptoms further gave a unique contribution in predicting gain of the intervention, independent of hippocampal volume. The results indicated that subjects with a stronger depressive symptom load benefited more from the training. A prediction model including baseline CA2/3-volume and depressive symptoms explained 42% of the variation in recall improvement. Our results are the first to suggest that hippocampal subfield volumetry is related to intervention outcomes in older adults experiencing memory problems. Also, previous studies have tended to exclude patients with concomitant depressive symptoms and memory complaints. The present results, however, strengthen the rationale and potential for cognitive intervention in these patients.

Memory training impacts short-term changes in aging white matter: a longitudinal diffusion tensor imaging study.

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging- and training-related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract-based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI-scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10-week interval. Further, group analysis demonstrated positive effects of training on the short-term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin-related processes in WM plasticity.

Amnesia following herpes simplex encephalitis: diffusion-tensor imaging uncovers reduced integrity of normal-appearing white matter.

PURPOSE: To explore white matter (WM) and gray matter tissue integrity in the apparently unaffected hemisphere of patients with herpes simplex encephalitis (HSE) who have gross unilateral medial temporal lobe (MTL) lesions and both verbal and visuospatial memory deficits. MATERIALS AND METHODS: This study had institutional ethics committee approval and included written informed consent. Magnetic resonance (MR) imaging was performed in five patients who had recovered from HSE (one woman, four men; median age, 32 years; interquartile range, 28.5-37 years) and 51 age-matched controls (30 women, 21 men; median age, 32 years; interquartile range, 28-37 years). As markers of microstructural WM integrity, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) derived from diffusion-tensor (DT) imaging were used. An automated regional brain segmentation approach yielded estimates of subcortical volumes, including hippocampus, and cortical thickness. Group differences were evaluated by using permutation tests. RESULTS: Examination of standard MR images found unilateral lesions in all patients. The patients with HSE showed reduced FA and increased MD and RD in several WM tracts contralateral to lesions (P < .05, corrected for multiple comparisons). Affected tracts included connections between the MTLs and other parts of the brain. No significant group differences were observed in subcortical volume or cortical thickness. CONCLUSION: These results suggest that patients with HSE have reduced microstructural integrity of normal-appearing WM contralateral to grossly visible lesions. These subtle lesions, detectable at DT imaging, probably contribute to the memory impairment manifested by these patients. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100179/-/DC1.

Effects of memory training on cortical thickness in the elderly.

The brain's ability to alter its functional and structural architecture in response to experience and learning has been extensively studied. Mental stimulation might serve as a reserve mechanism in brain aging, but macrostructural brain changes in response to cognitive training have been demonstrated in young participants only. We examined the short-term effects of an intensive memory training program on cognition and brain structure in middle-aged and elderly healthy volunteers. The memory trainers completed an 8-week training regimen aimed at improving verbal source memory utilizing the Method of Loci (MoL), while control participants did not receive any intervention. Both the memory trainers and the controls underwent magnetic resonance imaging (MRI) scans and memory testing pre and post 8 weeks of training or no training, respectively. Cortical thickness was automatically measured across the cortical mantle, and data processing and statistical analyses were optimized for reliable detection of longitudinal changes. The results showed that memory training improved source memory performance. Memory trainers also showed regional increases in cortical thickness compared with controls. Furthermore, thickness change in the right fusiform and lateral orbitofrontal cortex correlated positively with improvement in source memory performance, suggesting a possible functional significance of the structural changes. These findings demonstrate that systematic mental exercise may induce short-term structural changes in the aging human brain, indicating structural brain plasticity in elderly. The present study included short-term assessments, and follow-up studies are needed in order to assess whether such training indeed alters the long-term structural trajectories.

A double blind evaluation of cognitive decline in a Norwegian cohort of asymptomatic carriers of Huntington's disease.

Previous studies investigating subclinical signs of cognitive decline in presymptomatic carriers of Huntington's disease (HD) have shown conflicting results. The current study examines cognition in 105 at-risk individuals, using a broad neuropsychological test battery and adopting strict inclusion criteria for attaining a homogeneous sample. Results obtained by analyses of variance and effect size calculations indicate no clinical evidence of significant cognitive decline in asymptomatic HD carriers very far from onset of illness compared to noncarriers. Closeness to disease onset amongst gene carriers influenced cognition negatively whereas cytosine-adenine-guanine (CAG) repeat size did not. The findings call for longitudinal follow-up studies using a combination of clinical instruments and experimental paradigms to pinpoint when subtle cognitive deficits occur and within which of the cognitive domains.