Sarah Banks

Functional neuroimaging of mentalizing during the trust game in social anxiety disorder

Individuals with generalized social anxiety disorder tend to make overly negative and distorted predictions about social events, which enhance perceptions of threat and contribute to excessive anxiety in social situations. Here, we coupled functional magnetic resonance imaging and a multiround economic exchange game (‘trust game’) to probe mentalizing, the social-cognitive ability to attribute mental states to others. Relative to interactions with a computer, those with human partners (‘mentalizing’) elicited less activation of medial prefrontal cortex in generalized social anxiety patients compared with matched healthy control participants. Diminished medial prefrontal cortex function may play a role in the social-cognitive pathophysiology of social anxiety.

Self-awareness and self-monitoring of cognitive and behavioral deficits in behavioral variant frontotemporal dementia, primary progressive aphasia and probable Alzheimer's disease

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimers disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined.

Neuropsychiatric symptoms in behavioral variant frontotemporal dementia and primary progressive aphasia.

Neuropsychiatric symptoms are well defined in behavioral variant frontotemporal dementia but are not as well studied in primary progressive aphasia. This study compared caregiver reported neuropsychiatric symptoms in these 2 forms of dementia at short and long disease duration. Patients with behavioral variant frontotemporal dementia had more symptoms than patients with primary progressive aphasia. However, when divided by duration of disease, patients with primary progressive aphasia with long duration had a similar number of symptoms to patients with behavioral variant frontotemporal dementia at either duration. Furthermore, this group of patients with primary progressive aphasia had more symptoms typical of behavioral variant frontotemporal dementia and less mood-related symptoms which were more common in patients with primary progressive aphasia with shorter duration. This study illustrates the emergence of neuropsychiatric symptoms as primary progressive aphasia progresses and highlights the increasing overlap with behavioral variant frontotemporal dementia because the disease affects areas outside of the language network.

Serum α-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment

Objectives: Associations of past dietary vitamin E intake, past and current vitamin E supplement use, and current serum α-tocopherol levels, with memory (amnestic) and mixed-domain cognitive impairment in older women, ascertained from an in-depth neuropsychological assessment, were explored. Methods: This analysis used baseline data from 526 participants in a single-site ancillary study to the Womens Health Initiative, the Cognitive Change in Women study. Results: In bivariate analyses, neither past dietary vitamin E intake (<8 mg/day vs more) nor current vitamin E supplement use was associated with impairment. Women who did not use vitamin E supplements at Womens Health Initiative baseline had an increased risk of mixed-domain impairment (odds ratio [OR] 1.88; 95% CI 1.09 to 3.23). This association lost significance when adjusting for age, education, American National Adult Reading Test (ANART) score, and time between measurement of past vitamin E use and cognitive testing. Concurrent serum α-tocopherol had significant cross-sectional associations with both memory and mixed impairments, with women in the lowest quartile of serum α-tocopherol nearly twice as likely to show signs of memory (1.92; 1.24 to 2.97) and mixed-domain (2.01; 1.13 to 3.57) impairments. In multivariable models adjusting for age, education, and ANART score, the lowest quartile of serum α-tocopherol was associated with increased odds of memory impairment (OR 2.02; 1.27 to 3.20) and mixed impairments (OR 2.00; 1.04 to 3.85). Additional adjustment for APOE e4 did not affect these results. Conclusion: There was weak or no evidence of a protective effect of previous vitamin E intake on cognitive function. However, the association of low concurrent serum α-tocopherol with memory and mixed impairment merits further exploration.

Cognitive Deficits and Reduced Insight in Primary Progressive Aphasia

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA.

The Association between Montreal Cognitive Assessment Memory Scores and Hippocampal Volume in a Neurodegenerative Disease Sample

Despite widespread use, there have been few investigations into the neuroanatomical correlates of the Montreal Cognitive Assessment (MoCA). In a sample of 138 consecutive patients presenting with cognitive complaints, we report significant correlations between lower MoCA memory scores and smaller hippocampal volumes (r = 0.36–0.41, p < 0.001). We also report that the newly devised memory index score, designed to better capture encoding deficits than the standard delayed recall score, was not significantly better for predicting hippocampal volume. These initial results suggest that poor performance on the MoCA’s memory section should prompt further evaluation for hippocampal atrophy.

Multimodal MR Imaging Signatures of Cognitive Impairment in Active Professional Fighters

Purpose To investigate whether combining multiple magnetic resonance (MR) imaging modalities such as T1-weighted and diffusion-weighted MR imaging could reveal imaging biomarkers associated with cognition in active professional fighters. Materials and Methods Active professional fighters (n = 297; 24 women and 273 men) were recruited at one center. Sixty-two fighters (six women and 56 men) returned for a follow-up examination. Only men were included in the main analysis of the study. On the basis of computerized testing, fighters were separated into the cognitively impaired and nonimpaired groups on the basis of computerized testing. T1-weighted and diffusion-weighted imaging were performed, and volume and cortical thickness, along with diffusion-derived metrics of 20 major white matter tracts were extracted for every subject. A classifier was designed to identify imaging biomarkers related to cognitive impairment and was tested in the follow-up dataset. Results The classifier allowed identification of seven imaging biomarkers related to cognitive impairment in the cohort of active professional fighters. Areas under the curve of 0.76 and 0.69 were obtained at baseline and at follow-up, respectively, with the optimized classifier. The number of years of fighting had a significant (P = 8.8 × 10-7) negative association with fractional anisotropy of the forceps major (effect size [d] = 0.34) and the inferior longitudinal fasciculus (P = .03; d = 0.17). A significant difference was observed between the impaired and nonimpaired groups in the association of fractional anisotropy in the forceps major with number of fights (P = .03, d = 0.38) and years of fighting (P = 6 × 10-8, d = 0.63). Fractional anisotropy of the inferior longitudinal fasciculus was positively associated with psychomotor speed (P = .04, d = 0.16) in nonimpaired fighters but no association was observed in impaired fighters. Conclusion Without enforcement of any a priori assumptions on the MR imaging-derived measurements and with a multivariate approach, the study revealed a set of seven imaging biomarkers that were associated with cognition in active male professional fighters.

Neuropsychological Testing in Pathologically Verified Alzheimer Disease and Frontotemporal Dementia: How Well Do the Uniform Data Set Measures Differentiate Between Diseases?

Background/Aims: Differences in cognition between frontotemporal dementia (FTD) and Alzheimer disease (AD) are well described in clinical cohorts, but have rarely been confirmed in studies with pathologic verification. For emerging therapeutics to succeed, determining underlying pathology early in the disease course is increasingly important. Neuropsychological evaluation is an important component of the diagnostic workup for AD and FTD. Patients with FTD are thought to have greater deficits in language and executive function while patients with AD are more likely to have deficits in memory. Objectives: To determine if performance on initial cognitive testing can reliably distinguish between patients with frontotemporal lobar degeneration (FTLD) and AD neuropathology. In addition, are there other factors of the neuropsychological assessment that can be used to enhance the accuracy of underlying pathology? Methods: Using a logistic regression we retrospectively compared neurocognitive performance on initial evaluation of 106 patients with pathologically verified FTLD (pvFTLD), with 558 pathologically verified AD (pvAD) patients from the National Alzheimer’s Coordinating Center using data from the Uniform Data Set (UDS) and the neuropathology data set. Results: As expected, pvFTLD patients were younger, demonstrated better memory performance, and had more neuropsychiatric symptoms than pvAD patients. Other results were less predictable: pvFTLD patients performed better on one test of executive function (trail making test part B) but worse on another (digit span backward). Performance on language testing did not strongly distinguish the 2 groups. To determine what factors led to a misdiagnosis of AD in patients with FTLD, we further analyzed a small group of pvFTLD patients. These patients demonstrated older age and lower Neuropsychiatric Inventory Questionnaire counts compared with accurately diagnosed cases. Conclusions: Other than memory, numerical scores of neurocognitive performance on the UDS are of limited value in differentiating FTLD from AD at the initial visit. These results highlight the difficulty of obtaining an accurate early diagnosis of FTLD and argue for adding supplemental tests to those included in the UDS to assess cognition in FTD and AD patients.

MRI CLASSIFIERS CHARACTERIZE MILD TRAUMATIC BRAIN INJURY IN SYMPTOMATIC AND PRESYMPTOMATIC STAGES AND DIFFERENTIATE FROM ALZHEIMER’S DISEASE–RELATED IMPAIRMENT

Figure 1. Voxel based comparison of healthy volunteers separated into young (18 to 36) and older (38 to 71) age groups, compared to unimpaired and impaired retired boxers. Higher CV1 scores reflect greater expression of the pattern of atrophy shown at left. Young and older HV do not differ, Dix U. Meiberth, Xiaochen Hu, Ann-Katrin Schild, Annika Spottke, Frederic Brosseron, Katharina Buerger, Klaus Fliessbach, Michael T. Heneka, Ingo Kilimann, Christoph Laske, Oliver Peters, Josef Priller, Anja Schneider, Stefan J. Teipel, Jens Wiltfang, MichaelWagner, Emrah D€uzel, Frank Jessen and the DELCODE Study Group, Department of Psychiatry and Psychotherapy, University Hospital Cologne, Cologne, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Neurology, University of Bonn, Bonn, Germany; Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; Institute for Stroke and Dementia Research (ISD), Klinikum der Universit€at M€unchen, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; University Hospital Bonn, Bonn, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of T€ubingen, T€ubingen, Germany; German Center for Neurodegenerative Diseases (DZNE), T€ubingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charit e-Universitaetsmedizin Berlin, Berlin, Germany; Charit e Universit€atsmedizin Berlin & Berlin Institute of Health, Berlin, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany. Contact e-mail: dix.meiberth@uk-koeln.de

CAN TRAINED IMPROVISATION TECHNIQUES HELP REDUCE CAREGIVER BURDEN AND DEPRESSION

CDR 0.5; n1⁄411), mild (MMSE 22-30, CDR 0.5-1; n1⁄414), or moderate (MMSE 16-21, CDR 0.5-2; n1⁄48) AD. [F]GTP1 SUVR was measured in a meta-ROI that included the amygdala and the entorhinal, parahippocampal, fusiform, inferior temporal, and middle temporal cortices, using the cerebellar gray as reference. Results: Across the entire cohort, Spearman correlation analyses demonstrated associations between baseline [F]GTP1 SUVR and 12month longitudinal change on the MMSE (rs1⁄4-0.56, p<0.001), ADAS-Cog13 (rs1⁄40.63, p<0.001), RBANS z-score (rs1⁄4-0.49, p1⁄40.002), and CDR-SB (rs1⁄40.39, p1⁄40.011). These prognostic associations were primarily driven by the prodromal and mild AD cohorts, particularly on the ADAS-Cog13 (prodromal: rs1⁄40.69; mild: rs1⁄40.66) and RBANS z-score (prodromal: rs1⁄4-0.28; mild: rs1⁄40.54). After adjustments for baseline age and MMSE scores, baseline [F]GTP1 SUVR in the combined prodromal and mild AD groups continued to correlate with longitudinal decline on the ADAS-Cog13 (p1⁄40.005) and RBANS z-score (p1⁄40.008) Conclusions:These preliminary results confirm and extend prior findings suggesting the utility of tau PET signal in the temporal lobe as a prognostic biomarker in AD, particularly for prodromal and mild AD. More specific ROIs may yield further prognostic value at different stages of disease progression or for decline in individual cognitive domains.