Outcomes of Aural Rehabilitation Provided in Person or by Telehealth Among Deaf/Hard of Hearing Young Children with Cochlear Implants or Hearing Aids.

Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

Auditory Cortex Maturation and Language Development in Children with Hearing Loss and Additional Disabilities.

A significant portion of hearing-impaired children have additional disabilities, but data about the maturation of their auditory cortex are scarce. In these children, behavioral tests are often unreliable, and objective tests are needed for diagnostics and follow-up. This study aimed to explore auditory cortical maturation and language development, and the usability of an objective electroencephalogram-based biomarker in children with multiple disabilities. In 65 hearing aid and cochlear implant users (36 females; 36 with multiple disabilities; 44.3 ± 18.5 months of age, mean ± SD), auditory processing was examined using the P1 cortical auditory evoked response biomarker, and language development with the Preschool Language Scales 5th edition (PLS-5). During the study, all of the children received intensive extra language therapy for six months. No significant differences were found between the groups in P1 latency development, the proportion of abnormal P1 latencies, or the number of children whose P1 latencies changed from abnormal to normal during the study. The PLS-5 total language scores, auditory comprehension scores, or expressive communication scores did not differ between groups either. The P1 latencies showed meaningful negative correlations with the language scores. The results suggest that auditory cortex development is similar in hearing-impaired children with/without additional disabilities, and the P1 biomarker is a feasible tool to evaluate central auditory maturation in children with multiple disabilities.

Impacts of breast cancer and chemotherapy on gut microbiome, cognitive functioning, and mood relative to healthy controls.

Women diagnosed with breast cancer undergoing chemotherapy experience cognitive impairment, symptoms of anxiety and depression, and physical side effects including disruption in the diversity and community composition of the gut microbiome. To date, there is limited research exploring the associations among these specific challenges. The present cross-sectional study explored the associations of self-reported cognitive functioning, depression, and anxiety symptoms, and gut microbiome diversity and community composition in women who were diagnosed with and undergoing chemotherapy treatment for breast cancer (BC) compared to cancer-free healthy controls (HC). The BC group displayed higher rates of cognitive dysfunction (p < 0.001) and depressive symptoms (p < 0.05) relative to HC. There was a significant difference in microbiome community composition between BC and HC, particularly characterized by a decreased relative abundance of the mucin-degrading genus Akkermansia in BC compared to HC (p < 0.05). Association models identified significant associations among group, cognitive, depression, and microbiome variables (p < 0.001). Overall, the study identified that BC participants experienced significant differences in self-reported cognitive functioning, self-reported depression symptoms, microbiome community composition, and mucin-degrading bacteria of the gut-mucosal barrier, relative to HC. The present study is consistent with the hypothesis that gut microbiome community composition impacts a woman's experience with breast cancer and treatment suggesting that microbiome-based interventions have potential for improving quality of life outcomes in individuals with breast cancer.

Qualitative Study of Long-Term Cardiac Arrest Survivors' Challenges and Recommendations for Improving Survivorship.

Background Cardiac arrest survivorship refers to the lived experience of long-term survivors of cardiac arrest and the many postdischarge challenges they experience. We aimed to gather a nuanced understanding of these challenges and of survivors' perceptions of ways to improve the recovery process. Methods and Results We conducted 15 semistructured, one-on-one interviews with cardiac arrest survivor members of the Sudden Cardiac Arrest Foundation; the interviews were conducted by telephone and recorded and transcribed verbatim. We used thematic analysis, informed by the Framework Method, to identify underlying themes regarding cardiac arrest survivorship challenges and recommendations to improve cardiac arrest survivorship. Regarding challenges, the overarching theme was a feeling of unpreparedness to confront postarrest challenges because of lack of resources, education, and appropriate expectations for recovery. Regarding recommendations, we uncovered 3 overarching themes including systemic recommendations (eg, providing appropriate resources and expectations, educating providers about survivorship, following up with survivors, including caregivers in treatment planning), social recommendations (eg, attending peer support groups, spending time with loved ones, providing support resources for family members), and individual coping recommendations (eg, acceptance, resilience, regaining control, seeking treatment, focusing on meaning and purpose). Conclusions We described common challenges that survivors of cardiac arrest face, such as lacking resources, education, and appropriate expectations for recovery. Additionally, we identified promising pathways that may improve cardiac arrest survivorship at systemic, social, and individual coping levels. Future studies could use our findings as targets for interventions to support and improve survivorship.

The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness.

FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies.

Clinical and Molecular Correlates of Abnormal Changes in the Cerebellum and Globus Pallidus in Fragile X Premutation.

BACKGROUND: Fragile X premutation carriers (55-200 CGG triplets) may develop a progressive neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), after the age of 50. The neuroradiologic markers of FXTAS are hyperintense T2-signals in the middle cerebellar peduncle-the MCP sign. We recently noticed abnormal T2-signals in the globus pallidus in male premutation carriers and controls but the prevalence and clinical significance were unknown. METHODS: We estimated the prevalence of the MCP sign and pallidal T2-abnormalities in 230 male premutation carriers and 144 controls (aged 8-86), and examined the associations with FXTAS symptoms, CGG repeat length, and iron content in the cerebellar dentate nucleus and globus pallidus. RESULTS: Among participants aged ≥45 years (175 premutation carriers and 82 controls), MCP sign was observed only in premutation carriers (52 vs. 0%) whereas the prevalence of pallidal T2-abnormalities approached significance in premutation carriers compared with controls after age-adjustment (25.1 vs. 13.4%, p = 0.069). MCP sign was associated with impaired motor and executive functioning, and the additional presence of pallidal T2-abnormalities was associated with greater impaired executive functioning. Among premutation carriers, significant iron accumulation was observed in the dentate nucleus, and neither pallidal or MCP T2-abnormalities affected measures of the dentate nucleus. While the MCP sign was associated with CGG repeat length >75 and dentate nucleus volume correlated negatively with CGG repeat length, pallidal T2-abnormalities did not correlate with CGG repeat length. However, pallidal signal changes were associated with age-related accelerated iron depletion and variability and having both MCP and pallidal signs further increased iron variability in the globus pallidus. CONCLUSIONS: Only the MCP sign, not pallidal abnormalities, revealed independent associations with motor and cognitive impairment; however, the occurrence of combined MCP and pallidal T2-abnormalities may present a risk for greater cognitive impairment and increased iron variability in the globus pallidus.

Associations between posttraumatic stress symptoms and quality of life in cardiac arrest survivors and informal caregivers: A pilot survey study.

AIM: To estimate the proportion of significant posttraumatic stress (PTS) in both cardiac survivors with good neurologic recovery and informal caregivers, and to pilot test the hypothesis that greater PTS are associated with worse quality of life (QoL) in both cardiac arrest survivors and informal caregivers of cardiac arrest survivors. METHODS: We distributed an online survey to survivor and caregiver members of the Sudden Cardiac Arrest Foundation. Participants provided demographic and cardiac arrest characteristics and completed the PTSD Checklist-5 (PCL-5), the Lawton Instrumental Activities of Daily Living scale, and the WHOQOL-BREF. We identified covariates through bivariate correlations or linear regressions as appropriate. Six multiple regression models (three each for survivors and caregivers) examined associations between PCL-5 scores with each QoL subscale, adjusted for covariates identified from the bivariate models. RESULTS: We included 169 survivors (mean months since arrest: 62.8, positive PTS screen: 24.9%) and 52 caregivers (mean months since arrest: 43.2, positive PTS screen: 34.6%). For survivors, the following showed significant bivariate associations with QoL: Lawton scores, daily memory problems, sex, months since arrest, age, and income; for caregivers, months since arrest, age, and income. In adjusted models, greater PCL-5 scores were associated with worse QoL (ß: -0.35 to -0.53, p < .05). CONCLUSIONS: Our pilot results suggest that PTS are prevalent years after the initial cardiac arrest and are associated with worse QoL in survivors and informal caregivers. Further study is needed to validate these findings in a larger, representative sample.

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

BACKGROUND: A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses. METHODS: The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration. RESULTS: Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives. CONCLUSION: These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

Executive functioning as a predictor of stroke rehabilitation outcomes.

Objective: Stroke is a common cause of death and adult chronic neurologic disability. Although factors such as cardiovascular disease affect the incidence of stroke, less is known about factors influencing longitudinal stroke outcomes. The purpose of this research was to assess the contribution of executive functioning (EF) at discharge to the prediction of functional status at several timepoints between discharge from a stroke rehabilitation unit and 12 months, in comparison with depression, mental status, comorbidity, and pain at discharge, and daily functioning prior to admission. Methods: The sample comprised 246 inpatients aged 65 and older who were on inpatient rehabilitation services following acute hospitalization for a stroke. Patients (or proxies) were interviewed in person at discharge about their ability to engage in activities of daily living (ADL), and by telephone at follow-ups 3, 6, 9, and 12 months after discharge. Functional outcomes included independence in bathing, dressing, walking, use of the toilet, and chair/bed transfers. Hypotheses were tested concerning the relative contribution of EF, depression, mental status, comorbidity, and several other demographic and clinical variables to ADL performance. Results: Executive functioning, depression, and pre-admission ADL functioning were strong predictors of outcome at all five timepoints, while neither comorbidity nor mental status were retained in any regression models. Pain at discharge was a significant predictor at discharge and 6 month follow-up. Conclusions: Executive functioning and depression are robust predictors of functional status following stroke rehabilitation. Although not consistently a significant predictor, pain might also be a useful addition to predictive models.

3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats.

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.

3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial.

BACKGROUND: Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms. AIMS: This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams. METHODS: Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session. RESULTS: In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of -26.3 (29.5) for 125 mg, -24.4 (24.2) for 100 mg, and -11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set ( p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up ( p<0.001) with 76% ( n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated. CONCLUSIONS: Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.

Harnessing centred identity transformation to reduce executive function burden for maintenance of health behaviour change: the Maintain IT model.

The inability to produce sustainable lifestyle modifications (e.g., physical activity, healthy diet) remains a major barrier to reducing morbidity and mortality from prevalent, preventable conditions. The objective of this paper is to present a model that builds on and extends foundational theory and research to suggest novel approaches that may help to produce lasting behaviour change. The model aims to integrate factors not typically examined together in order to elucidate potential processes underlying a shift from behaviour initiation to long-term maintenance. The central premise of the Maintain IT model builds on approaches demonstrating that in-tact executive function (EF) is critical for health behaviour initiation, for more complex behaviours beyond initiation, and in unsupportive environments and circumstances, but successful recruitment of EF is effortful and prone to error. Enduring changes are more likely if the underlying cognitive processes can become less effortful (non-conscious, automatic). The Maintain IT model posits that a centred identity transformation is one path leading to less effortful processing and facilitating successful recruitment of EF when necessary over the long term, increasing the sustainability of health behaviour change. A conceptual overview of the literature supporting the utility of this integrative model, future directions, and anticipated challenges are presented.

Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning.

OBJECTIVES: To clarify the neuropsychiatric phenotype of fragile X-associated tremor/ataxia syndrome (FXTAS), and assess the extent to which it is mediated by the dysexecutive syndrome that is a major feature of the disorder. METHODS: We examined the prevalence of clinically meaningful psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, in comparison with men with a normal allele. Measures included the Neuropsychiatric Inventory (NPI), Symptom Checklist-90-R (SCL-90-R), and the Behavioral Dyscontrol Scale, a measure of executive functioning. Between-group differences were evaluated using logistic regression, followed by a mediation analysis with ordinary least squares regression to assess the contribution of dysexecutive syndrome to the observed psychiatric domains. RESULTS: Men with FXTAS showed higher rates of clinically significant symptoms overall and in specific domains: somatization, obsessive compulsive, depression, anxiety, psychoticism, agitation/aggression, apathy/indifference, irritability, and nighttime behavior problems. Post hoc analyses suggested that findings of psychoticism among men with FXTAS may be associated with participants' accurate acknowledgment of cognitive and physical dysfunction, rather than reflecting psychosis. Asymptomatic carriers showed no evidence of clinically significant psychiatric symptoms, but when all carriers were compared with men having a normal FMR1 allele, executive function deficits were found to mediate scores in several domains on both NPI and SCL-90-R. CONCLUSIONS: Building on prior research, the results provide evidence that the psychiatric phenotype for men includes clinically meaningful depression, hostility, and irritability, in association with behavioral and attentional disinhibition. It is likely that these problems reflect the effects of impaired executive functioning.

Fragile X-associated tremor/ataxia syndrome: another phenotype of the fragile X gene.

OBJECTIVE: Neuropsychologists have an important role in evaluating patients with fragile X-associated disorders, but most practitioners are unaware of the recently identified neurodegenerative movement disorder known as fragile X-associated tremor ataxia syndrome (FXTAS). The objective of this editorial is to orient the reader to FXTAS and highlight the importance of clinical neuropsychology in describing the fragile X premutation phenotype and the role practitioners may have in assessing and monitoring patients with or at risk for neurodegeneration. METHOD: We issued a call for papers for the special issue, highlighting the primary objective of familiarizing clinical neuropsychologists with FXTAS, and with the neuropsychological phenotype of both male and female asymptomatic carriers. RESULTS: Eight papers are included, including an overview of the fragile X-associated disorders (Grigsby), a review of the neuroradiological and neurological aspects of FXTAS and how the disorder compares to other movement disorders (O'Keefe et al.), a perspective on the prominence of white matter disease and dementia in FXTAS (Filley), and a review of mouse models of FXTAS (Foote). There are four research papers, including one on self-reported memory problems in FXTAS (Birch et al.), and three papers focused on the neuropsychiatric aspects of the fragile X premutation, a review (Bourgeois), an examination of autism-related traits (Schneider), and a research paper on executive functioning and psychopathology (Grigsby). CONCLUSIONS: The issue highlights the importance of awareness of fragile X-associated disorders for neuropsychologists, an awareness that must reach beyond neurodevelopmental aspects related to fragile X syndrome into the realm of neurodegenerative disease and aging.

Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder caused by a repeat expansion in the fragile X mental retardation 1 (FMR1) gene. The disorder is characterized by kinetic tremor and cerebellar ataxia, shows age-dependent penetrance, and occurs more frequently in men. This paper summarizes the key emerging issues in FXTAS as presented at the Second International Conference on the FMR1 Premutation: Basic Mechanisms & Clinical Involvement in 2015. The topics discussed include phenotype-genotype relationships, neurobehavioral function, and updates on FXTAS genetics and imaging.

The fragile X mental retardation 1 gene (FMR1): historical perspective, phenotypes, mechanism, pathology, and epidemiology.

OBJECTIVES: To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS) for neuropsychologists. METHODS: Selective review of the literature on FXTAS. RESULTS: FXTAS is an X-linked neurodegenerative disorder of late onset. One of several phenotypes associated with different mutations of the fragile X mental retardation 1 gene (FMR1), FXTAS involves progressive action tremor, gait ataxia, and impaired executive functioning, among other features. It affects carriers of the FMR1 premutation, which may expand when passed from a mother to her children, in which case it is likely to cause fragile X syndrome (FXS), the most common inherited developmental disability. CONCLUSION: This review briefly summarizes current knowledge of the mechanisms, epidemiology, and mode of transmission of FXTAS and FXS, as well as the neuropsychological, neurologic, neuropsychiatric, neuropathologic, and neuroradiologic phenotypes of FXTAS. Because it was only recently identified, FXTAS is not well known to most practitioners, and it remains largely misdiagnosed, despite the fact that its prevalence may be relatively high.

Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial.

Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS.

Managing Problems Before Problems Manage You.

Every day we face problems, both personal and professional, and our initial reaction determines how well we solve those problems. Whether a problem is minor or major, short-term or lingering, there are techniques we can employ to help manage the problem and the problem-solving process. This article, based on my book Don't Tick Off The Gators! Managing Problems Before Problems Manage You, presents 12 different concepts for managing problems, not "cookie cutter" solutions, but different ideas that you can apply as they fit your circumstances.

White matter disease and cognitive impairment in FMR1 premutation carriers.

OBJECTIVE: This cross-sectional, observational study examined the role of white matter involvement in the cognitive impairment of individuals with the fragile X mental retardation 1 (FMR1) premutation. METHODS: Eight asymptomatic premutation carriers, 5 participants with fragile X tremor/ataxia syndrome (FXTAS), and 7 noncarrier controls were studied. The mean age of the asymptomatic premutation carriers, participants with FXTAS, and noncarrier controls was 60, 71, and 67 years, respectively. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to examine the middle cerebellar peduncles (MCP) and the genu and splenium of the corpus callosum in relation to executive function and processing speed. MRS measures were N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine, and fractional anisotropy (FA) was used for DTI. Executive function was assessed with the Behavioral Dyscontrol Scale and the Controlled Oral Word Association Test (COWAT), and processing speed with the Symbol Digit Modalities Test. RESULTS: Among all 13 FMR1 premutation carriers, significant correlations were found between N-acetyl aspartate/creatine and choline/creatine in the MCP and COWAT scores, and between FA in the genu and performance on the Behavioral Dyscontrol Scale, COWAT, and Symbol Digit Modalities Test; a correlation was also found between FA in the splenium and COWAT performance. In all regions studied, participants with FXTAS had the lowest mean FA. CONCLUSION: Microstructural white matter disease as determined by MRS and DTI correlated with executive dysfunction and slowed processing speed in these FMR1 premutation carriers. Neuroimaging abnormalities in the genu and MCP suggest that disruption of white matter within frontocerebellar networks has an important role in the cognitive impairment associated with the FMR1 premutation.

Effects of pioglitazone or exercise in older adults with mild cognitive impairment and insulin resistance: a pilot study.

AIMS: To examine the effects of pioglitazone or endurance exercise training on cognitive function in older adults with mild cognitive impairment (MCI) and insulin resistance. METHODS: Seventy-eight adults (mean age ± SD: 65 ± 7 years) with central obesity and MCI were randomized to 6 months of endurance exercise, pioglitazone or control. RESULTS: Sixty-six participants completed the study. Exercise training did not significantly increase peak oxygen uptake compared to control (p = 0.12). Compared to control, insulin resistance improved in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25). There was no measureable effect of pioglitazone or exercise on cognitive performance compared to control. CONCLUSION: In this pilot study, pioglitazone improved insulin resistance but not cognitive performance in older adults with MCI and insulin resistance.