Joint transformer architecture in brain 3D MRI classification: its application in Alzheimer's disease classification.

Alzheimer's disease (AD), a neurodegenerative disease that mostly affects the elderly, slowly impairs memory, cognition, and daily tasks. AD has long been one of the most debilitating chronic neurological disorders, affecting mostly people over 65. In this study, we investigated the use of Vision Transformer (ViT) for Magnetic Resonance Image processing in the context of AD diagnosis. ViT was utilized to extract features from MRIs, map them to a feature sequence, perform sequence modeling to maintain interdependencies, and classify features using a time series transformer. The proposed model was evaluated using ADNI T1-weighted MRIs for binary and multiclass classification. Two data collections, Complete 1Yr 1.5T and Complete 3Yr 3T, from the ADNI database were used for training and testing. A random split approach was used, allocating 60% for training and 20% for testing and validation, resulting in sample sizes of (211, 70, 70) and (1378, 458, 458), respectively. The performance of our proposed model was compared to various deep learning models, including CNN with BiL-STM and ViT with Bi-LSTM. The suggested technique diagnoses AD with high accuracy (99.048% for binary and 99.014% for multiclass classification), precision, recall, and F-score. Our proposed method offers researchers an approach to more efficient early clinical diagnosis and interventions.

Sex differences in Parkinson disease-associated episodic memory and processing speed deficits.

OBJECTIVES: This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete. METHODS: One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups. RESULTS: Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding. CONCLUSIONS: Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.

Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias.

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) and its metabolites (acid-labile (e.g., iron-sulfur clusters) and bound (e.g., per-, poly-) sulfides) have been shown to modulate both vascular and neuronal homeostasis. We recently reported that elevated plasma sulfides were associated with cognitive dysfunction and measures of microvascular disease in ADRD. Here we extend our previous work to show associations between elevated sulfides and magnetic resonance-based metrics of brain atrophy and white matter integrity. Elevated bound sulfides were associated with decreased grey matter volume, while increased acid labile sulfides were associated with decreased white matter integrity and greater ventricular volume. These findings are consistent with alterations in sulfide metabolism in ADRD which may represent maladaptive responses to oxidative stress.

Cortical oscillatory dysfunction in Parkinson disease during movement activation and inhibition.

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

The emerging postural instability phenotype in idiopathic Parkinson disease.

Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson's Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.

Blood glutamine synthetase signaling in alcohol use disorder and racial disparity.

As of 2018, 14.4 million adults ages 18 and older in the U.S had alcohol use disorder (AUD). However, only about 8% of adults who had AUD in the past year received treatment. Surveys have also shown racial disparities regarding AUD treatments. Thus, it is imperative to identify racial disparities in AUD patients, as it may indicate a specific underlying pathophysiology in an AUD subpopulation. To identify racial disparity in AUD, we enrolled 64 cohorts, including 26 AUD participants and 38 healthy controls, from Northwest Louisiana using community-based enrollment. Then, we used psychometric scales to assess alcohol drinking patterns and measured blood metabolites change using LC-MS/MS. Alcohol-related scales from the questionnaires did not differ between the Caucasian AUD participants and African-American AUD participants. From blood metabolomics analyses, we identified that 6 amino acids were significantly different by AUD status and or race. Interestingly, Caucasian AUD participants had a higher glutamate metabolism mediated by glutamine synthetase (GS). The correlation between blood glutamate/glutamine ratio and GS activity was only significant in the Caucasian AUD group whereas no changes were observed in African-American AUD group or controls. Taken together, our findings from this sample population demonstrate that blood GS is a potential biomarker associated with Caucasian AUD, which is an important step towards the application of a new pharmacological treatment for AUD.

Alzheimer Disease and Related Dementia Resources: Perspectives of African American and Caucasian Family Caregivers in Northwest Louisiana.

We examined knowledge of Alzheimer's disease and related dementias (ADRD), resources, and research opportunities among older African American (AA) and Caucasian caregivers. A mixed methods design integrated qualitative (focus group) and quantitative (survey) data from Northwest Louisiana. Eight focus groups (59 adults, 92% female, 78% AA, 25% rural) revealed limited knowledge. Quantitative findings from 117 ADRD caregivers (83% female, 72% AA, 30% limited heath literacy, 27% low income) indicated participants obtained information from providers (54%), friends and relatives (32%), and the internet (37%). Barriers to care were cost (24%) and lack of family agreement (17%). Few families used adult daycare (8%) or support groups (28%). Concerns about research participation were violation of privacy (30%) and fear of patient distress (27%). Distrust of doctors was minimal (3%). Findings did not vary by race. There is a need for clear, literacy-appropriate information about ADRD, caregiver resources, and clinical trials.

Neuroimaging and Neuropsychological Outcomes Following Clinician-Delivered Cognitive Training for Six Patients With Mild Brain Injury: A Multiple Case Study.

Nearly half of all mild brain injury sufferers experience long-term cognitive impairment, so an important goal in rehabilitation is to address their multiple cognitive deficits to help them return to prior levels of functioning. Cognitive training, or the use of repeated mental exercises to enhance cognition, is one remediation method for brain injury. The primary purpose of this hypothesis-generating pilot study was to explore the statistical and clinical significance of cognitive changes and transfer of training to real-life functioning following 60 h of Brain Booster, a clinician-delivered cognitive training program, for six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI). The secondary purpose was to explore changes in functional connectivity and neural correlates of cognitive test gains following the training. We used a multiple case study design to document significant changes in cognitive test scores, overall IQ score, and symptom ratings; and we used magnetic resonance imaging (MRI) to explore trends in functional network connectivity and neural correlates of cognitive change. All cognitive test scores showed improvement with statistically significant changes on five of the seven measures (long-term memory, processing speed, reasoning, auditory processing, and overall IQ score). The mean change in IQ score was 20 points, from a mean of 108 to a mean of 128. Five themes emerged from the qualitative data analysis including improvements in cognition, mood, social identity, performance, and Instrumental Activities of Daily Living (IADLs). With MRI, we documented significant region-to-region changes in connectivity following cognitive training including those involving the cerebellum and cerebellar networks. We also found significant correlations between changes in IQ score and change in white matter integrity of bilateral corticospinal tracts (CST) and the left uncinate fasciculus. This study adds to the growing body of literature examining the effects of cognitive training for mild TBI and ABI, and to the collection of research on the benefits of cognitive training in general. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918994.

Time course of cognitive training in Parkinson disease.

BACKGROUND: People with Parkinson disease (PD) have difficulty initiating internally generated movements. We have shown that computer-based cognitive training can improve movement initiation. However, little is known about the optimal duration of training. OBJECTIVES: To determine the optimal training duration for computer-based neurorehabilitation of internally represented movement initiation in people with PD. METHODS: Nineteen PD and twenty-one age-matched control participants, ages 50-85 years, were included in analysis of pre- and post-training evaluation and 30 training sessions. Computer training consisted of cued and un-cued movement trials. The presentation of a cue (a combination of numbers on either the right, left or both sides of the screen) indicated that participants should respond by typing the numbers. Successful cued trials were followed by un-cued trials consisting of a green filled circle. Participants re-enter the cued sequence, thus producing an internally represented (IR) movement. The training was adaptive. Outcome measures were reaction time and error rate, and cumulative sum (CUSUM) analysis was used to identify peak training improvement. RESULTS: Participants with PD were divided into impaired (IPD) and unimpaired (UPD) groups, based on mean control group pre-training performance. All three groups showed improved RT and error rates for IR trials; however, the IPD group demonstrated significantly greater improvement in reaction time. Training was most effective in participants with greater disease severity and duration. Peak day of training improvement for the IPD group was 8 days. CONCLUSION: Optimal training duration was relatively short and the IPD group demonstrated the most gain, indicating that cognitive training should be tailored to individual needs.

Altered Cortico-Limbic Network Connectivity in Parkinsonian Depression: The Effect of Antidepressants.

BACKGROUND: Depression is a common comorbidity of Parkinson's disease (PD); however, the impact of antidepressant status on cortical function in parkinsonian depression is not fully understood. While studies of resting state functional MRI in major depression have shown that antidepressant treatment affects cortical connectivity, data on connectivity and antidepressant status in PD is sparse. OBJECTIVE: We tested the hypothesis that cortico-limbic network (CLN) resting state connectivity is abnormal in antidepressant-treated parkinsonian depression. METHODS: Thirteen antidepressant-treated depressed PD and 47 non-depressed PD participants from the Parkinson's Progression Markers Initiative (PPMI) database were included. Data was collected using 3T Siemens TIM Trio MR scanners and analyzed using SPM and CONN functional connectivity toolbox. Volumetric analysis was also performed using BrainSuite. RESULTS: We found decreased connectivity in the antidepressant-treated depressed PD group when compared to non-depressed PD between the left frontal operculum and bilateral insula, and also reduced connectivity between right orbitofrontal cortex and left temporal fusiform structures. Increased depression scores were associated with decreased insular-frontal opercular connectivity. No ROI volumetric differences were found between groups. CONCLUSION: Given the relationship between depression scores and cortico-limbic connectivity in PD, the abnormal insular-frontal opercular hypoconnectivity in this cohort may be associated with persistent depressive symptoms or antidepressant effects.

Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson's Disease.

While a small subset of Parkinson's disease cases have genetic causes, most cases are sporadic and may have an environmental contributor that has largely remained enigmatic. Remarkably, gastrointestinal symptoms in PD patients serve as a prodrome for the eventual motor dysfunctions. Herein, we review studies exploring a possible link between the gastric human pathogen Helicobacter pylori and PD. We provide plausible and testable hypotheses for how this organism might contribute to PD: 1) a toxin(s) produced by the bacteria; 2) disruption of the intestinal microbiome; 3) local inflammation that crosses the gut-brain axis, leading to neuroinflammation; and 4) manipulation of the pharmacokinetics of the PD drug levodopa by H. pylori, even in those not receiving exogenous levodopa. Key findings are: 1) people with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD; 2) H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients; 3) eradication of H. pylori improves motor function in PD patients over PD patients whose H. pylori was not eradicated; and 4) eradication of H. pylori improves levodopa absorption in PD patients compared to that of PD patients whose H. pylori was not eradicated. Evidence is accumulating that H. pylori has a link with PD, but the mechanism is unclear. Future work should explore the effects of H. pylori on development of PD in defined PD animal models, focusing on the roles of H. pylori toxins, inflammation, levodopa absorption, and microbiome dysbiosis.

Impact of Prehospital Transportation on Survival in Skiers and Snowboarders with Traumatic Brain Injury.

INTRODUCTION: Prehospital helicopter use and its impact on outcomes in snowboarders and skiers incurring traumatic brain injury (TBI) is unknown. The present study investigates the association of helicopter transport with survival of snowboarders and skiers with TBI, in comparison with ground emergency medical services (EMS), by using data derived from the National Trauma Data Bank (2007-2014). METHODS: Primary and secondary endpoints were defined as in-hospital survival and absolute risk reduction based upon number needed to transport (treat) respectively. Multivariable regression models including traditional logit model, model fitted with generalized estimating equations, and those incorporating results from propensity score matching methods were used to investigate the association of helicopter transport with survival compared with ground EMS. RESULTS: Of the 1018 snowboarders and skiers who met the criteria, 360 (35.4%) were transported via helicopters whereas 658 (64.6%) via ground EMS with a mortality rate of 1.7% and 1.5%, respectively. Multivariable log-binomial models demonstrated association of prehospital helicopter transport with increased survival (odds ratio 8.58; 95% confidence interval 1.09-67.64; P = 0.041; absolute risk reduction: 10.06%). This finding persisted after propensity score matching (odds ratio 24.73; 95% confidence interval 5.74-152.55; P < 0.001). The corresponding absolute risk reduction implies that approximately 10 patients need to be transported via helicopter to save 1 life. CONCLUSIONS: Based on our robust statistical analysis of retrospective data, our findings suggest prehospital helicopter transport improved survival in patients incurring TBI after snowboard- or ski-related falls compared with those transported via ground EMS. Policies directed at using helicopter services at remote winter resorts or ski or snowboarding locations should be implemented.

A pilot study to evaluate multi-dimensional effects of dance for people with Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease associated with deficits in motor, cognitive, and emotion/quality of life (QOL) domains, yet most pharmacologic and behavioral interventions focus only on motor function. Our goal was to perform a pilot study of Dance for Parkinson's-a community-based program that is growing in popularity-in order to compare effect sizes across multiple outcomes and to inform selection of primary and secondary outcomes for a larger trial. Study participants were people with PD who self-enrolled in either Dance for Parkinson's classes (intervention group, N=8) or PD support groups (control group, N=7). Assessments of motor function (Timed-Up-and-Go, Gait Speed, Standing Balance Test), cognitive function (Test of Everyday Attention, Verbal Fluency, Alternate Uses, Digit Span Forward and Backward), and emotion/QOL (Geriatric Depression Scale, Falls Efficacy Scale-International, Parkinson's Disease Questionnaire-39 (total score and Activities of Daily Living subscale)) were performed in both groups at baseline and follow-up. Standardized effect sizes were calculated within each group and between groups for all 12 measures. Effect sizes were positive (suggesting improvement) for all 12 measures within the intervention group and 7 of 12 measures within the control group. The largest between-group differences were observed for the Test of Everyday Attention (a measure of cognitive switching), gait speed and falls efficacy. Our findings suggest that dance has potential to improve multiple outcomes in people with PD. Future trials should consider co-primary outcomes given potential benefits in motor, cognitive and emotion/QOL domains.

Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes.

Parkinsonian syndromes share clinical signs including akinesia/bradykinesia and rigidity, which are consequences of pathology involving dopaminergic substantia nigra neurons. Yet cognitive and psychiatric disturbances are common, even early in the course of disease. Executive dysfunction is often measurable in newly diagnosed Parkinson's disease. Treatment with dopaminergic medications, particularly dopamine agonists, has been associated with hallucinations and impulse control disorder. Older age, presence of APOE-4 gene, and/or other factors result in amyloid plaque deposition that, in turn, accelerates cortical Lewy body plus tau pathology, linking Dementia with Lewy Bodies and Parkinson's disease with early dementia with Alzheimer's disease. Treatments available for cognitive deficits, depression, and psychotic symptoms are discussed.

White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control.

Perceived and performance-based executive dysfunction in Parkinson's disease.

Executive dysfunction is common in early stage Parkinson's disease (PD). We evaluated the relationship between self- and informant-report measurement of real-world executive functions as well as performance-based neuropsychological measures in mildly cognitively impaired individuals with PD and healthy controls. The PD group reported more difficulty with initiation of complex tasks compared to caregiver ratings, and processing speed was a strong predictor of self-reported executive dysfunction for the PD group, followed by depression. Processing speed and semantic verbal fluency predicted informant-reported executive dysfunction in PD. These findings highlight the contribution of speeded processing for performance of everyday executive tasks in PD.

Movement activation and inhibition in Parkinson's disease: a functional imaging study.

BACKGROUND: Parkinson's disease (PD), traditionally considered a movement disorder, has been shown to affect executive function such as the ability to adapt behavior in response to new environmental situations. OBJECTIVE: to identify the impact of PD on neural substrates subserving two specific components of normal movement which we refer to as activation (initiating an un-cued response) and inhibition (suppressing a cued response). METHODS: We used fMRI to measure pre-movement processes associated with activating an un-cued response and inhibiting a cued response plan in 13 PD (ON anti-parkinsonian medications) and 13 control subjects. Subjects were shown a visual arrow cue followed by a matched or mismatched response target that instructed them to respond with a right, left, or bilateral button press. In mismatched trials, an un-cued (new) response was initiated, or the previously cued response was suppressed. RESULTS: We were able to isolate pre-movement responses in dorsolateral prefrontal cortex, specifically in the right hemisphere. During the activation of an un-cued movement, PD subjects showed decreased activity in the putamen and increased cortical activity in bilateral DLPFC, SMA, subcentral gyrus and inferior frontal operculum. During inhibition of a previously cued movement, the PD group showed increased activation in SMA, S1/M1, premotor and superior parietal areas. CONCLUSION: Right DLPFC plays a role in pre-movement processes, and DLPFC activity is abnormal in PD. Decreased specificity of responses was observed in multiple ROI's. The basal ganglia are involved in circuits that coordinate activation and inhibition involved in action selection as well as execution.

The contribution of trail making to the prediction of performance-based instrumental activities of daily living in Parkinson's disease without dementia.

Performance on Part B of the Trail Making Test (TMT) contributes to the prediction of ability to complete instrumental activities of daily living (IADLs) in Parkinson's disease (PD). Although this suggests that cognitive flexibility is important in the everyday functioning of individuals with PD, this may not be the case as the TMT is multifactorial, involving motor speed, visual scanning, sequencing, and cognitive flexibility. The purpose of the current study was to determine which elements of the task contribute to the prediction of IADLs in a sample of 30 nondemented individuals with PD. Correlational analyses indicated strong relationships between a performance-based measure of IADLs and measures involving scanning, sequencing, and cognitive flexibility from the Delis-Kaplan Executive Function System (D-KEFS) TMT. Results from standard regressions indicated that measures of sequencing and level of depression but not scanning, cognitive flexibility, or demographic variables made a significant, independent contribution to the prediction of IADLs. These results suggest that the sequencing element of the TMT is paramount in the prediction of IADLs in PD.

Hemispheric asymmetries and prosodic emotion recognition deficits in Parkinson's disease.

While Parkinson's disease (PD) has traditionally been described as a movement disorder, there is growing evidence of cognitive and social deficits associated with the disease. However, few studies have looked at multi-modal social cognitive deficits in patients with PD. We studied lateralization of both prosodic and facial emotion recognition (the ability to recognize emotional valence from either tone of voice or from facial expressions) in PD. The Comprehensive Affect Testing System (CATS) is a well-validated test of human emotion processing that has been used to study emotion recognition in several major clinical populations, but never before in PD. We administered an abbreviated version of CATS (CATS-A) to 24 medicated PD participants and 12 age-matched controls. PD participants were divided into two groups, based on side of symptom onset and unilateral motor symptom severity: left-affected (N = 12) or right-affected PD participants (N = 12). CATS-A is a computer-based button press task with eight subtests relevant to prosodic and facial emotion recognition. Left-affected PD participants with inferred predominant right-hemisphere pathology were expected to have difficulty with prosodic emotion recognition since there is evidence that the processing of prosodic information is right-hemisphere dominant. We found that facial emotion recognition was preserved in the PD group, however, left-affected PD participants had specific impairment in prosodic emotion recognition, especially for sadness. Selective deficits in prosodic emotion recognition suggests that (1) hemispheric effects in emotion recognition may contribute to the impairment of emotional communication in a subset of people with PD and (2) the coordination of neural networks needed to decipher temporally complex social cues may be specifically disrupted in PD.