Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.

OBJECTIVES: To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). METHODS: Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups. RESULTS: Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD. INTERPRETATION: AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109.

Prevalence of Cognitive and Vestibular Impairment in Seniors Experiencing Falls.

BACKGROUND: Falls are a growing concern in seniors (≥65 yrs). Cognitive impairment (CI) and vestibular impairment (VI) increase fall risk. The aim of this study is to assess the prevalence of CI and VI in seniors experiencing falls. METHODS: Participants (≥65 yrs) with falls were recruited from Falls Prevention Programs (FPPs) and a Memory Clinic (MC). CI was assessed using the Montreal Cognitive Assessment at FPPs. VI was assessed at an MC and FFPs using the Head Impulse- (video + bedside), Headshake-, Dix-Hallpike test, and test of sensory interaction in balance. Questionnaires included Dizziness Handicap Inventory (DHI) and Activities-specific Balance Confidence Scale (ABC). RESULTS: Of 41 participants (29 FPPs, 12 MC); mean age was 80.1 ± 7.1 years, and 58.5% were female. Overall, 82.9% had VI. At FPPs, 76.0% had CI, and 72.3% had CI + VI. Bilateral vestibular hypofunction (BVH) was more common than unilateral vestibular hypofunction (UVH) (70.6% vs. 29.4%); p = 0.016. Dizziness Handicap (DHI) was not different between those with a VI (23.5 ± 23.9) versus without VI [PVI + no impairment] (10.0 ± 15.4); p = 0.160. Balance confidence (ABC) was lowest in VI but not significantly different between those with a VI (63.4 ± 27.3) versus without VI [PVI + no impairment] (85.0 ± 16.5); p = 0.053. CONCLUSIONS: VI and CI are prevalent in seniors experiencing falls. For seniors with history of falls, both cognitive and vestibular functions should be considered in the assessment and subsequent treatment. Screening enables earlier detection, targeted interventions, and prevention, reducing the clinical and financial impact.

Vestibular Exercises as a Fall Prevention Strategy in Patients with Cognitive Impairment.

Vestibular impairment (VI) and cognitive impairment (CI) are risk factors for senior falls. We tested the feasibility of a self-directed 12-week vestibular rehabilitation (VR) program in Memory Clinic patients (65 years+) with a fall, CI and VI. We assessed recruitment, exercise adherence and ability to complete questionnaires/assessments. Twelve patients with CI and falls were screened and 8/12 (75% - prevalence) had VI. All patients completed the screening tests/questionnaires (100% - completeness); 7/8 patients were recruited (87.5% - recruitment); 1/7 (85.7% - attrition) patient attended follow-up. VI is prevalent in patients with CI experiencing falls but traditional VR is not feasible, so a novel delivery of VR must be explored.

Les exercices de réadaptation vestibulaire comme stratégie de prévention des chutes chez des patients atteints de troubles cognitifs. Les troubles vestibulaires (TV) et les troubles cognitifs (TC) sont des facteurs de risque de chute chez les personnes âgées. À cet égard, nous avons évalué le caractère réalisable d'un programme autonome de réadaptation vestibulaire de 12 semaines offert, dans une clinique de la mémoire, à des patients âgés de 65 ans et plus ayant chuté au moins une fois et qui sont atteints de TV et de TC. Nous nous sommes ainsi penchés sur leur recrutement, leur adhésion aux exercices du programme et leur capacité à compléter des questionnaires d'évaluation. Douze patients aux prises avec des TC ont été examinés. De ce nombre, huit d'entre eux (75 %) étaient aussi atteints de TV. Tous ces patients ont complété des tests de dépistage ainsi que des questionnaires, lesquels ont été remplis dans 100 % des cas. Au total, sept patients sur huit ont été recrutés, soit 87,5 %, tandis qu'un seul, ce qui représente un taux d'attrition de 85,7 %, s'est présenté lors d'un suivi. Même si les TV affectent les patients atteints de TC, un programme de réadaptation vestibulaire n'est pas réellement réalisable dans ce contexte, de sorte qu'un nouveau programme devrait être exploré.

Progression of neuropsychiatric and cognitive features due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene: a case report.

Physical symptoms of myoclonus dystonia due to epsilon-sarcoglycan mutations are well documented; however, the progression of neuropsychiatric and cognitive symptoms remains unclear. We present a case of a 34-year-old woman with early childhood onset of myoclonic jerks, dystonic posture and developmental delay due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene. Over time, she developed neuropsychiatric symptoms. She underwent bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus for her motor symptoms, which greatly improved but she exhibited slow deterioration of her neuropsychiatric and cognitive symptoms, particularly apathy, aggression and severe executive dysfunction.

18F-Flortaucipir (AV1451) imaging identifies grey matter atrophy in retired athletes.

BACKGROUND: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning. METHODS: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [18F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels). RESULTS: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played. CONCLUSION: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration.

Investigating the use of plasma pTau181 in retired contact sports athletes.

BACKGROUND: Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration. METHODS: Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging. RESULTS: Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (ß = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10-3 mm2/s vs. 0.90 ± 0.03 × 10-3 mm2/s, p = 0.003; CC axial diffusivity: 1.49 ± 0.04 × 10-3 mm2/s vs. 1.41 ± 0.02 × 10-3 mm2/s, p < 0.001, respectively). CONCLUSIONS: Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.

Progression of neuropsychiatric symptoms in young-onset versus late-onset Alzheimer's disease.

Young-onset and late-onset Alzheimer's disease has different clinical presentations with late-onset presenting most often with memory deficits while young-onset often presents with a non-amnestic syndrome. However, it is unknown whether there are differences in presentation and progression of neuropsychiatric symptoms in young- versus late-onset Alzheimer's disease. We aimed to investigate differences in the prevalence and severity of neuropsychiatric symptoms in patients with young- and late-onset Alzheimer's disease longitudinally with and without accounting for the effect of medication usage. Sex differences were also considered in these patient groups. We included 126 young-onset and 505 late-onset Alzheimer's disease patients from National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). We investigated the prevalence and severity of neuropsychiatric symptoms using the Neuropsychiatric Inventory-Questionnaire over 4 visits with 1-year intervals, using a linear mixed-effects model. The prevalence of depression was significantly higher in young-onset than late-onset Alzheimer's disease over a 4-year interval when antidepressant usage was included in our analyses. Our findings suggest that neuropsychiatric symptom profiles of young- and late-onset Alzheimer's disease differ cross-sectionally but also display significant differences in progression.

PET Tau Imaging and Motor Impairments Differ Between Corticobasal Syndrome and Progressive Supranuclear Palsy With and Without Alzheimer's Disease Biomarkers.

Introduction: Frontotemporal lobar degeneration (FTLD)-related syndrome includes progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). PSP is usually caused by a tauopathy but can have associated Alzheimer's disease (AD) while CBS can be caused by tauopathy, transactive response DNA binding protein 43 kDa, or AD pathology. Our aim was to compare the parkinsonian syndromes presenting without AD biomarkers (CBS/PSP-non-AD) to parkinsonian syndromes with AD biomarkers (CBS/PSP-AD). Materials and Methods: Twenty-four patients [11 males, 13 females; age (68.46 ± 7.23)] were recruited for this study. The whole cohort was divided into parkinsonian syndromes without AD biomarkers [N = 17; diagnoses (6 CBS, 11 PSP)] and parkinsonian syndromes with AD biomarkers [N = 7; diagnoses (6 CBS-AD, 1 PSP-AD)]. Anatomical MRI and PET imaging with tau ligand [18F]-AV1451 tracer was completed. Cerebrospinal fluid analysis or [18F]-AV1451 PET imaging was used to assess for the presence of AD biomarkers. Progressive supranuclear palsy rating scale (PSPRS) and unified Parkinson's disease rating scale (UPDRS) motor exam were implemented to assess for motor disturbances. Language and cognitive testing were completed. Results: The CBS/PSP-non-AD group [age (70.18 ± 6.65)] was significantly older (p = 0.028) than the CBS/PSP-AD group [age (64.29 ± 7.32)]. There were no differences between the groups in terms of gender, education, years of disease duration, and disease severity as measured with the Clinical Dementia Rating scale. The CBS/PSP-non-AD group had significantly lower PET Tau Standard Volume Uptake Ratio (SUVR) values compared to the CBS/PSP-AD group in multiple frontal and temporal areas, and inferior parietal (all p < 0.03). The CBS/PSP-non-AD group had significantly higher scores compared to the CBS/PSP-AD group on PSPRS (p = 0.004) and UPDRS motor exam (p = 0.045). The CBS/PSP-non-AD group had higher volumes of inferior parietal, precuneus, and hippocampus (all p < 0.02), but lower volume of midbrain (p = 0.02), compared to the CBS/PSP-AD group. Discussion: The CBS/PSP-non-AD group had higher motor disturbances compared to the CBS/PSP-AD group; however, both groups performed similarly on neuropsychological measures. The AD biomarker group had increased global uptake of PET Tau SUVR and lower volumes in AD-specific areas. These results show that the presenting phenotype of CBS and PSP syndromes and the distribution of injury are strongly affected by the presence of AD biomarkers.

Association Between Social Cognition Changes and Resting State Functional Connectivity in Frontotemporal Dementia, Alzheimer's Disease, Parkinson's Disease, and Healthy Controls.

OBJECTIVE: To determine the relationship between alterations in resting state functional connectivity and social cognition dysfunction among patients with frontotemporal dementia (FTD), Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC). METHODS: Fifty-seven participants (FTD = 10, AD = 18, PD = 19, and HC = 10) underwent structural and functional imaging and completed the Awareness of Social Inference Test-Emotion Evaluation Test (TASIT-EET), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, Revised Self-Monitoring Scale (RSMS), Interpersonal Reactivity Index (IRI), and Social Norms Questionnaire (SNQ). A multi-variate pattern analysis (MVPA) was carried out to determine activation differences between the groups. The clusters from the MVPA were used as seeds for the ROI-to-voxel analysis. Relationship between social cognition deficits and uncinate integrity was also investigated. RESULTS: BOLD signal activation differed among the four groups of AD, PD, FTD, and HC in the left inferior temporal gyrus-anterior division [L-ITG (ant)], right central opercular cortex (R-COp), right supramarginal gyrus, posterior division (R-SMG, post), right angular gyrus (R-AG), and R-ITG. The BOLD co-activation of the L-ITG (ant) with bilateral frontal pole (FP) and paracingulate gyrus was positively associated with IRI-perspective taking (PT) (r = 0.38, p = 0.007), SNQ total (r = 0.37, p = 0.009), and TASIT-EET (r = 0.47, p < 0.001). CONCLUSION: Patients with neurodegenerative diseases showed alterations in connectivity in brain regions important for social cognition compared with HCs. Functional connectivity correlated with performance on social cognition tasks and alterations could be responsible for some of the social cognition deficits observed in all neurodegenerative diseases.

Elevated cerebrospinal fluid total tau in former professional athletes with multiple concussions.

OBJECTIVE: To identify CSF biomarkers that are related to decreased white matter (WM) integrity and poor cognitive performance in former professional athletes with a history of multiple concussions. METHODS: Concentrations of phosphorylated tau181, total tau (t-tau), and ß-amyloid in the CSF were measured in 3 groups: 22 former professional athletes with multiple concussions (mean ± SD age 55.9 ± 12.2 years), 5 healthy controls (age 57.4 ± 5.2 years), and 12 participants (age 60.0 ± 6.6 years) diagnosed with Alzheimer disease (AD). All participants in the former athletes group underwent diffusion tensor imaging to determine WM tract integrity and completed neuropsychological testing. We divided the former athletes group into those with normal (<300 pg/mL) and high (>300 pg/mL) CSF t-tau. RESULTS: CSF t-tau in the former athletes group was significantly higher than in the healthy control group (349.3 ± 182.6 vs 188.8 ± 39.9 pg/mL, p = 0.003) and significantly lower than in the patients with AD (349.3 ± 182.6 vs 857.0 ± 449.3 pg/mL, p = 0.007). Fractional anisotropy values across all the tracts were significantly lower in the high CSF t-tau group compared to the normal CSF t-tau group (p = 0.036). Participants in the high CSF t-tau group scored significantly lower on the Trail Making Test (TMT) Part B compared to the normal CSF t-tau group (t scores 45.6 ± 18.8 vs 62.3 ± 10.1, p = 0.017). CONCLUSION: Our findings indicate that former athletes with multiple concussions are at increased risk of elevated levels of CSF t-tau and that high CSF t-tau is associated with reduced WM integrity and worse scores on the TMT Part B.

Emotion Detection Deficits and Decreased Empathy in Patients with Alzheimer's Disease and Parkinson's Disease Affect Caregiver Mood and Burden.

Background: Changes in social cognition occur in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and can be caused by several factors, including emotion recognition deficits and neuropsychiatric symptoms (NPS). The aims of this study were to investigate: (1) group differences on emotion detection between patients diagnosed with AD or PD and their respective caregivers; (2) the association of emotion detection with empathetic ability and NPS in individuals with AD or PD; (3) caregivers' depression and perceived burden in relation to patients' ability to detect emotions, empathize with others, presence of NPS; and (4) caregiver's awareness of emotion detection deficits in patients with AD or Parkinson. Methods: In this study, patients with probable AD (N = 25) or PD (N = 17), and their caregivers (N = 42), performed an emotion detection task (The Awareness of Social Inference Test-Emotion Evaluation Test, TASIT-EET). Patients underwent cognitive assessment, using the Behavioral Neurology Assessment (BNA). In addition, caregivers completed questionnaires to measure empathy (Interpersonal Reactivity Index, IRI) and NPS (Neuropsychiatric Inventory, NPI) in patients and self-reported on depression (Geriatric Depression Scale, GDS) and burden (Zarit Burden Interview, ZBI). Caregivers were also interviewed to measure dementia severity (Clinical Dementia Rating (CDR) Scale) in patients. Results: The results suggest that individuals with AD and PD are significantly worse at recognizing emotions than their caregivers. Moreover, caregivers failed to recognize patients' emotion recognition deficits and this was associated with increased caregiver burden and depression. Patients' emotion recognition deficits, decreased empathy and NPS were also related to caregiver burden and depression. Conclusions: Changes in emotion detection and empathy in individuals with AD and PD has implications for caregiver burden and depression and may be amenable to interventions with both patients and caregivers.

MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer's Disease.

Clinical diagnosis of Alzheimer's disease (AD) prior to the age of 65 years is classified as young-onset (YOAD), whereas diagnosis after the age of 65 years is considered late-onset (LOAD). Although rare autosomal mutations more commonly associate with YOAD, most YOAD and LOAD cases are sporadic. YOAD and LOAD share amyloid and tau pathology, but many YOAD patients show increased disease severity and rate of progression. The current study examined the microRNA (miRNA) expression profile from exosomes isolated from the cerebrospinal fluid (CSF) of YOAD patients with biomarker-confirmed AD. Results uncovered miR-16-5p, miR-125b-5p, miR-451a, and miR-605-5p as differentially expressed in the CSF-derived exosomes of YOAD patients when compared with healthy controls (HC). In a cohort of LOAD patients, miR-125b-5p, miR-451a, and miR-605-5p were similarly altered in expression, but miR-16-5p showed similar expression to control. Analysis of the mRNA targets of these miRNAs revealed transcripts enriched in biological processes relevant to the post-mortem posterior cingulate cortex transcriptome in YOAD from a previously published microarray study, including those related to neuron projections, synaptic signaling, metabolism, apoptosis, and the immune system. Hence, these miRNAs represent novel targets for uncovering disease mechanisms and for biomarker development in both YOAD and LOAD.

Decreased Number of Self-Paced Saccades in Post-Concussion Syndrome Associated with Higher Symptom Burden and Reduced White Matter Integrity.

The aim of this study was to examine the potential utility of a self-paced saccadic eye movement as a marker of post-concussion syndrome (PCS) and monitoring the recovery from PCS. Fifty-nine persistently symptomatic participants with at least two concussions performed the self-paced saccade (SPS) task. We evaluated the relationships between the number of SPSs and 1) number of self-reported concussion symptoms, and 2) integrity of major white matter (WM) tracts (as measured by fractional anisotropy [FA] and mean diffusivity) that are directly or indirectly involved in saccadic eye movements and often affected by concussion. These tracts included the uncinate fasciculus (UF), cingulum (Cg) and its three subcomponents (subgenual, retrosplenial, and parahippocampal), superior longitudinal fasciculus, and corpus callosum. Mediation analyses were carried out to examine whether specific WM tracts (left UF and left subgenual Cg) mediated the relationship between the number of SPSs and 1) interval from last concussion or 2) total number of self-reported symptoms. The number of SPSs was negatively correlated with the total number of self-reported symptoms (r = -0.419, p = 0.026). The number of SPSs were positively correlated with FA of left UF and left Cg (r = 0.421, p = 0.013 and r = 0.452, p = 0.008; respectively). FA of the subgenual subcomponent of the left Cg partially mediated the relationship between the total number of symptoms and the number of SPSs, while FA of the left UF mediated the relationship between interval from last concussion and the number of SPSs. In conclusion, SPS testing as a fast and objective assessment may reflect symptom burden in patients with PCS. In addition, since the number of SPSs is associated with the integrity of some WM tracts, it may be useful as a diagnostic biomarker in patients with PCS.

The relationship between brain atrophy and cognitive-behavioural symptoms in retired Canadian football players with multiple concussions.

Multiple concussions, particularly in contact sports, have been associated with cognitive deficits, psychiatric impairment and neurodegenerative diseases like chronic traumatic encephalopathy. We used volumetric and deformation-based morphometric analyses to test the hypothesis that repeated concussions may be associated with smaller regional brain volumes, poorer cognitive performance and behavioural symptoms among former professional football players compared to healthy controls. This study included fifty-three retired Canadian Football League players, 25 age- and education-matched healthy controls, and controls from the Cambridge Centre for Aging and Neuroscience database for validation. Volumetric analyses revealed greater hippocampal atrophy than expected for age in former athletes with multiple concussions than controls and smaller left hippocampal volume was associated with poorer verbal memory performance in the former athletes. Deformation-based morphometry confirmed smaller bilateral hippocampal volume that was associated with poorer verbal memory performance in athletes. Repeated concussions may lead to greater regional atrophy than expected for age.

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Random Item Generation Is Affected by Age.

Purpose: Random item generation (RIG) involves central executive functioning. Measuring aspects of random sequences can therefore provide a simple method to complement other tools for cognitive assessment. We examine the extent to which RIG relates to specific measures of cognitive function, and whether those measures can be estimated using RIG only. Method: Twelve healthy older adults (age: M = 70.3 years, SD = 4.9; 8 women and 4 men) and 20 healthy young adults (age: M = 24 years, SD = 4.0; 12 women and 8 men) participated in this pilot study. Each completed a RIG task, along with the color Stroop test, the Repeatable Battery for the Assessment of Neuropsychological Status, and the Peabody Picture Vocabulary Test-Fourth Edition (Dunn & Dunn, 2007). Several statistical features extracted from RIG sequences, including recurrence quantification, were found to be related to the other measures through correlation, regression, and a neural-network model. Results: The authors found significant effects of age in RIG and demonstrate that nonlinear machine learning can use measures of RIG to accurately predict outcomes from other tools. Conclusions: These results suggest that RIG can be used as a relatively simple predictor for other tools and in particular seems promising as a potential screening tool for selective attention in healthy aging.

Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech.

PURPOSE: Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech. METHOD: We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics). RESULTS: We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech. CONCLUSIONS: Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

The association between white-matter tract abnormalities, and neuropsychiatric and cognitive symptoms in retired professional football players with multiple concussions.

Retired professional athletes, who have suffered repetitive concussions, report symptoms of depression, anxiety, and memory impairment over time. Moreover, recent imaging data suggest chronic white-matter tract deterioration in sport-related concussion. The aim of this study is to evaluate the impact of repetitive concussions in retired professional football players on white-matter tracts, and relate these changes to neuropsychological function. All subjects (18 retired professional football players and 17 healthy controls) underwent imaging, neuropsychological assessment, and reported on concussion-related symptoms. Whole brain tract-based spatial statistics analysis revealed increased axial diffusivity in the right hemisphere of retired players in the (1) superior longitudinal fasciculus (SLF), (2) corticospinal tract, and (3) anterior thalamic radiations, suggesting chronic axonal degeneration in these tracts. Moreover, retired players report significantly higher neuropsychiatric and cognitive symptoms than healthy controls, and worsening of these symptoms since their last concussion. Loss of integrity in the right SLF significantly correlated with participants' visual learning ability. In sum, these results suggest that repetitive concussions in retired professional football players are associated with focal white-matter tract abnormalities that could explain some of the neuropsychiatric symptoms and cognitive deficits experienced by these retired athletes.