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1.
Clin Gerontol ; : 1-12, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37767999

ABSTRACT

OBJECTIVES: Determine strategies and resources used by VA Home-Based Primary Care (HBPC) teams to discuss firearm safety and suicide risk with older veterans and their families or caregivers. Training and resource needs for promoting firearm safety with older veterans were also ascertained. METHODS: Ten focus groups (N = 37) were conducted virtually in 2022 with HBPC directors and psychologists. Qualitative rapid response coding identified domains and themes within transcripts. RESULTS: Analysis revealed three major domains: firearm safety, suicide risk, and resources/trainings. Firearm safety themes included discussions during clinical procedures, firearm-related challenges, veteran culture, and barriers and facilitators to effective conversations. Suicide risk themes included assessment procedures, frequency/types of risk conversations, factors related to suicidal ideation/behavior, challenges, and strategies to enhance communication. Resource/training themes included those currently used and perceived needs. CONCLUSIONS: Participants described strategies for facilitating firearm safety and suicide prevention discussions with older veterans, their families, and caregivers. Using respectful language and attending to values related to firearm ownership were identified as essential. CLINICAL IMPLICATIONS: Additional clinician/staff training/resources are needed for addressing older veteran firearm safety and suicide risk, including how to conduct more effective conversations with older veterans on these topics and better engage families/caregivers in prevention efforts.

2.
Heliyon ; 9(8): e18943, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37609394

ABSTRACT

Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD.

3.
Aging Ment Health ; 27(2): 399-407, 2023 02.
Article in English | MEDLINE | ID: mdl-35006021

ABSTRACT

Objectives: Worry has been shown to have a negative impact on many aspects of neurocognitive performance. Interestingly, research indicates mindfulness both improves aspects of cognitive ability and reduces worry symptoms. Yet, the impact of mindfulness on the relationship between worry and cognition has yet to be explored. Based on research discussed herein, we hypothesize that those with higher levels of dispositional mindfulness will have better cognitive performance than those with lower levels of dispositional mindfulness, regardless of worry level. The present study investigated the potential moderating influence of mindfulness on the relationship between worry and cognitive performance.Methods: The sample included 113 older veterans who were screened at the VA Palo Alto Health Care System in Palo Alto, CA. Cognitive domains of interest included learning and memory, processing speed, attention, working memory, and executive function. Mindfulness was assessed with the Five Facet Mindfulness Questionnaire (FFMQ), and worry symptoms were assessed using the Penn State Worry Questionnaire (PSWQ). Hypotheses were tested with multiple regression analyses using the Hayes (2003) PROCESS macro.Results: Contrary to what was hypothesized, only mindful awareness significantly moderated the relationship between worry and processing speed.Conclusion: This finding has important implications for introducing mindfulness techniques into older adults' routines to decrease worry and mitigate its negative effects on processing speed.


Subject(s)
Mindfulness , Humans , Aged , Mindfulness/methods , Anxiety/therapy , Anxiety/psychology , Cognition , Attention , Executive Function
4.
J Gerontol A Biol Sci Med Sci ; 78(3): 554-560, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36099058

ABSTRACT

BACKGROUND: The diagnosis of mild cognitive impairment (MCI) presents a critical period for intervention. Although exercise and cognitive training (CT) interventions have reported independent success in improving cognition, some meta-analyses have suggested that combined interventions provide maximal benefits. Much previous research has studied land-based as opposed to water-based exercise, which places potential barriers on older adults. The purpose of the current study was to examine the impact of combined exercise (water- or land-based) and CT treatment on cognition for older adults with MCI. METHODS: Participants were 67 adults ages 54-86 years classified with MCI who engaged in 6 months of land or aquatic-based exercise with subsequent CT over 4 weeks. Primary outcome variables were performance measures of several cognitive domains across 3-time points (baseline, following exercise intervention, and following CT intervention). Linear mixed effects modeling examined exercise group differences across time periods in an intention-to-treat analysis. RESULTS: Both aquatic- and land-based exercise with CT interventions resulted in significant improvement in learning and memory outcomes, though improvement in executive functioning, processing speed, language, and visuospatial abilities was limited to water-based and CT treatment groups. Differences in linear growth patterns between groups were nonsignificant. CONCLUSION: Results suggest that for older adults with MCI to obtain global cognitive benefits (ie, learning and memory, executive functioning, processing speed, language, and visuospatial abilities) using combined exercise and CT interventions, they must be able to fully engage in exercise, and aquatic-based activities should be further considered.


Subject(s)
Cognitive Dysfunction , Cognitive Training , Humans , Aged , Aged, 80 and over , Cognitive Dysfunction/diagnosis , Cognition , Executive Function , Exercise , Exercise Therapy/methods
5.
J Alzheimers Dis ; 85(4): 1593-1600, 2022.
Article in English | MEDLINE | ID: mdl-34958013

ABSTRACT

BACKGROUND: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition. OBJECTIVE: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities. METHODS: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group). RESULTS: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up. CONCLUSION: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.


Subject(s)
Cognitive Dysfunction/therapy , Comorbidity , Transcranial Magnetic Stimulation/instrumentation , Veterans/statistics & numerical data , Aged , Alzheimer Disease/psychology , Female , Humans , Male , Neuropsychological Tests/statistics & numerical data , Pilot Projects , Treatment Outcome
6.
Clin Neuropsychol ; 36(7): 1679-1690, 2022 10.
Article in English | MEDLINE | ID: mdl-33349171

ABSTRACT

ObjectiveThe Verbal Naming Test (VNT) assesses word-finding ability, or naming, through the use of a naming-to-definition paradigm and has been shown to effectively detect naming deficits in older adults. This study evaluated the convergent and discriminant validity of the VNT, assessed how well it detects Mild Cognitive Impairment (MCI), and provided descriptive data stratified by three levels of age (60-69, 70-79, 80-89).MethodThe sample included 151 healthy older Veterans who were found to be cognitively intact and free of neurological and acute psychiatric disorders (mean age = 74.23, SD = 6.67; range: 60-89) and 39 older Veterans with MCI (mean age = 72.97, SD = 8.24; range 60-88). Correlations were calculated between the VNT, Boston Naming Test (BNT), and several other neuropsychological measures. ROC analyses determined how well the VNT detected MCI.ResultsThe VNT correlated with the Rey Auditory Verbal Learning Test and the Logical Memory test. The BNT did not correlate with any measure with the exception of Judgment of Line Orientation (JLO). The Area Under the Curve (AUC) for the detection of MCI was 0.69. Normative data for the VNT are presented and stratified by ages.ConclusionsThis study provides evidence of the convergent and discriminant validity of the Verbal Naming Test in a sample of cognitively normal older adults, as well as its validity in the detection of MCI. It also provides descriptive data on the Verbal Naming Test that can be used in the neuropsychological assessment of older adults.


Subject(s)
Cognitive Dysfunction , Veterans , Aged , Cognitive Dysfunction/diagnosis , Humans , Judgment , Language Tests , Neuropsychological Tests
7.
Nature ; 600(7889): 494-499, 2021 12.
Article in English | MEDLINE | ID: mdl-34880498

ABSTRACT

Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration1. The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus2-4, yet little is known about the factors and mechanisms that mediate these effects. Here we show that 'runner plasma', collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a concerted increase in complement cascade inhibitors including clusterin (CLU). Intravenously injected CLU binds to brain endothelial cells and reduces neuroinflammatory gene expression in a mouse model of acute brain inflammation and a mouse model of Alzheimer's disease. Patients with cognitive impairment who participated in structured exercise for 6 months had higher plasma levels of CLU. These findings demonstrate the existence of anti-inflammatory exercise factors that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans who engage in exercise.


Subject(s)
Alzheimer Disease , Encephalitis , Alzheimer Disease/metabolism , Animals , Clusterin/genetics , Clusterin/metabolism , Endothelial Cells/metabolism , Humans , Mice , Proteomics
8.
Alzheimers Dement ; 17(11): 1808-1817, 2021 11.
Article in English | MEDLINE | ID: mdl-34297895

ABSTRACT

INTRODUCTION: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking. METHODS: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants. RESULTS: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations. DISCUSSION: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.


Subject(s)
Amnesia/therapy , Cognitive Dysfunction/therapy , Exercise , Pamphlets , Patient Selection , Aged , Cognition , Female , Humans , Male , Postal Service
9.
Ann Oncol ; 32(5): 631-641, 2021 05.
Article in English | MEDLINE | ID: mdl-33539946

ABSTRACT

BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Antineoplastic Combined Chemotherapy Protocols , Humans , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Nivolumab/adverse effects , Progression-Free Survival , Small Cell Lung Carcinoma/drug therapy
10.
Fed Pract ; 38(1): 28-34, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33574646

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care. METHODS: Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS. RESULTS: A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures. CONCLUSIONS: The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.

11.
Int Psychogeriatr ; 32(7): 807-813, 2020 07.
Article in English | MEDLINE | ID: mdl-31739820

ABSTRACT

This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.


Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Sleep Wake Disorders/genetics , Tandem Repeat Sequences/genetics , Actigraphy , Aged , Aged, 80 and over , Circadian Rhythm , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Sleep , Sleep Wake Disorders/physiopathology
12.
J Autism Dev Disord ; 49(6): 2447-2460, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30937735

ABSTRACT

We examined language profiles of 2571 children, 30-68 months old, with autism spectrum disorder (ASD), other developmental disabilities (DD), and typical development from the general population (POP). Children were categorized as expressive dominant (ED), receptive dominant (RD), or nondominant (ND). Within each group, the ED profile was the least frequent. However, children in the ASD group were more likely to display an ED profile than those in the DD or POP groups, and these children were typically younger, had lower nonverbal cognitive skills, and displayed more severe social-affect symptoms of ASD compared to their peers with RD or ND profiles. These findings have research and clinical implications related to the focus of interventions targeting young children with ASD and other DDs.


Subject(s)
Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Child Development/physiology , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Language , Autism Spectrum Disorder/epidemiology , Case-Control Studies , Child , Child, Preschool , Female , Humans , Language Development Disorders/epidemiology , Male
13.
JAMA Psychiatry ; 75(9): 884-893, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29955803

ABSTRACT

Importance: Treatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans. Objective: To determine the efficacy of rTMS in the treatment of TRMD in veterans. Design, Setting, and Participants: A double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated. Interventions: Participants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions. Main Outcomes and Measures: The primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ≤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life. Results: The 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission. Conclusions and Relevance: A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population. Trial Registration: ClinicalTrials.gov Identifier: NCT01191333.


Subject(s)
Depressive Disorder, Treatment-Resistant , Quality of Life , Suicide Prevention , Suicide , Transcranial Magnetic Stimulation/methods , Veterans/psychology , Adult , Depressive Disorder, Treatment-Resistant/diagnosis , Depressive Disorder, Treatment-Resistant/psychology , Depressive Disorder, Treatment-Resistant/therapy , Double-Blind Method , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Psychiatric Status Rating Scales , Stress Disorders, Post-Traumatic/diagnosis , Suicide/psychology , Treatment Outcome , United States , Veterans Health
14.
Trials ; 18(1): 409, 2017 09 02.
Article in English | MEDLINE | ID: mdl-28865495

ABSTRACT

BACKGROUND: Evaluation of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) in Veterans offers unique clinical trial challenges. Here we describe a randomized, double-blinded, intent-to-treat, two-arm, superiority parallel design, a multicenter study funded by the Cooperative Studies Program (CSP No. 556) of the US Department of Veterans Affairs. METHODS: We recruited medical providers with clinical expertise in treating TRMD at nine Veterans Affairs (VA) medical centers as the trial local investigators. We plan to enroll 360 Veterans diagnosed with TRMD at the nine VA medical centers over a 3-year period. We will randomize participants into a double-blinded clinical trial to left prefrontal rTMS treatment or to sham (control) rTMS treatment (180 participants each group) for up to 30 treatment sessions. All participants will meet Diagnostic and statistical manual of mental disorders, 4 th edition (DSM-IV) criteria for major depression and will have failed at least two prior pharmacological interventions. In contrast with other rTMS clinical trials, we will not exclude Veterans with posttraumatic stress disorder (PTSD) or history of substance abuse and we will obtain detailed history regarding these disorders. Furthermore, we will maintain participants on stable anti-depressant medication throughout the trial. We will evaluate all participants on a wide variety of potential predictors of treatment response including cognitive, psychological and functional parameters. DISCUSSION: The primary dependent measure will be remission rate (Hamilton Rating Scale for Depression (HRSD24) ≤ 10), and secondary analyses will be conducted on other indices. Comparisons between the rTMS and the sham groups will be made at the end of the acute treatment phase to test the primary hypothesis. The unique challenges to performing such a large technically challenging clinical trial with Veterans and potential avenues for improvement of the design in future trials will be described. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01191333 . Registered on 26 August 2010. This report is based on the protocol version 4.6 amended in February 2016. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.


Subject(s)
Affect , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/therapy , Prefrontal Cortex/physiopathology , Transcranial Direct Current Stimulation , Clinical Protocols , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/psychology , Depressive Disorder, Treatment-Resistant/diagnosis , Depressive Disorder, Treatment-Resistant/physiopathology , Depressive Disorder, Treatment-Resistant/psychology , Double-Blind Method , Humans , Neuropsychological Tests , Remission Induction , Research Design , Surveys and Questionnaires , Time Factors , Transcranial Direct Current Stimulation/adverse effects , Treatment Outcome , United States , United States Department of Veterans Affairs
15.
PLoS One ; 12(1): e0170564, 2017.
Article in English | MEDLINE | ID: mdl-28114393

ABSTRACT

OBJECTIVE: Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI. METHOD: We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls). RESULTS: While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls. CONCLUSIONS: The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders.


Subject(s)
Brain Injuries, Traumatic/pathology , Caudate Nucleus/pathology , Stress Disorders, Post-Traumatic/pathology , Veterans , Adult , Aged , Brain Injuries, Traumatic/diagnostic imaging , Caudate Nucleus/diagnostic imaging , Cognition Disorders , Diffusion Tensor Imaging , Female , Humans , Male , Middle Aged , Stress Disorders, Post-Traumatic/diagnostic imaging
16.
BMJ Open ; 6(4): e011589, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-27084290

ABSTRACT

INTRODUCTION: Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. METHODS AND ANALYSIS: The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the 'Suspend before low' feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. ETHICS AND DISSEMINATION: Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. TRIAL REGISTRATION NUMBER: ACTRN12614000510640, Pre-results.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/drug therapy , Hypoglycemia/prevention & control , Insulin Infusion Systems , Insulin/administration & dosage , Monitoring, Physiologic/methods , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/blood , Glycated Hemoglobin/metabolism , Hormones/blood , Humans , Hypoglycemic Agents/administration & dosage , Insulin/therapeutic use , Insulin Infusion Systems/adverse effects , Ketosis , Outcome Assessment, Health Care , Quality of Life , Safety , Treatment Outcome , Young Adult
17.
Gerontologist ; 56(1): 72-81, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26220415

ABSTRACT

PURPOSE OF THE STUDY: With the influx of veterans entering older adulthood, it is increasingly important to understand risk factors for cognitive decline. Posttraumatic stress disorder (PTSD) and the metabolic syndrome (MetS) are highly prevalent in older veterans. Although both increase risk for cognitive decline and often co-occur, it is unclear how they may interact to negatively impact cognition. The aim of this cross-sectional study was to investigate associations among PTSD, MetS, and cognitive function in older veterans. We hypothesized that co-occurring PTSD and MetS would be associated with worse cognitive performance than seen in either illness alone. DESIGN AND METHODS: Participants completed cognitive testing to assess processing speed, verbal memory, and executive function. Data from 204 male veterans aged 55-89 were analyzed with the use of hierarchical multiple regression models. RESULTS: Veterans with MetS demonstrated poorer performance on tasks of executive function (response inhibition and cognitive set shifting) and immediate verbal memory regardless of PTSD status. There was an interaction between MetS and PTSD on delayed verbal memory, suggesting that the negative impact of MetS on verbal memory was only significant for veterans not classified as having PTSD. IMPLICATIONS: This is the first study to examine the impact of comorbid PTSD and MetS on cognition. The results suggest that MetS is associated with poorer verbal learning and executive functioning independent of PTSD. We discuss the necessity of monitoring cerebrovascular risk factors and providing early behavioral and/or pharmaceutical interventions to lessen the risk of cognitive decline in older age.


Subject(s)
Cognition/physiology , Cognitive Aging/psychology , Executive Function/physiology , Metabolic Syndrome/psychology , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Memory , Metabolic Syndrome/complications , Middle Aged , Neuropsychological Tests , Retrospective Studies , Stress Disorders, Post-Traumatic/complications
18.
J Rehabil Res Dev ; 53(6): 781-796, 2016.
Article in English | MEDLINE | ID: mdl-28273324

ABSTRACT

Veterans who have been deployed to combat often have complex medical histories including some combination of traumatic brain injury (TBI); mental health problems; and other chronic, medically unexplained symptoms (i.e., chronic multisymptom illness [CMI] clusters). How these multiple pathologies relate to functional health is unclear. In the current study, 120 Veterans (across multiple combat cohorts) underwent comprehensive clinical evaluations and completed self-report assessments of mental health symptoms (Patient Health Questionnaire-2 [PHQ-2], PTSD Checklist-Civilian Version [PCL-C]) and functional health (Veterans Rand 36-Item Health Survey). Canonical correlation and regression modeling using split-sample permutation tests revealed that the PHQ-2/PCL-C composite variable (among TBI severity and number of problematic CMI clusters) was the primary predictor of multiple functional health domains. Two subscales, Bodily Pain and General Health, were associated with multiple predictors (TBI, PHQ-2/PCL-C, and CMI; and PHQ-2/PCL-C and CMI, respectively), demonstrating the multifaceted nature of how distinct medical problems might uniquely and collectively impair aspects of functional health. Apart from these findings, however, TBI and CMI were not predictors of any other aspects of functional health. Taken together, our findings suggest that mental health problems might exert ubiquitous influence over multiple domains of functional health. Thus, screening of mental health problems and education and promotion of mental health resources can be important to the treatment and care of Veterans.


Subject(s)
Health Status , Mental Health , Veterans Health , Adult , Aged , Brain Injuries, Traumatic/epidemiology , Depression/epidemiology , Female , Humans , Male , Middle Aged , Stress Disorders, Post-Traumatic/epidemiology , Surveys and Questionnaires , Veterans
19.
J Int Neuropsychol Soc ; 21(3): 239-48, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25801537

ABSTRACT

Naming or word-finding tasks are a mainstay of the typical neuropsychological evaluation, particularly with older adults. However, many older adults have significant visual impairment and there are currently no such word-finding tasks developed for use with older visually impaired populations. This study presents a verbal, non-visual measure of word-finding for use in the evaluation of older adults with possible dysnomia. Stimuli were chosen based on their frequency of usage in everyday spoken language. A 60-item scale was created and given to 131 older Veterans. Rasch analyses were conducted and differential item functioning assessed to eliminate poorly-performing items. The final 55-item scale had a coefficient alpha of 0.84 and correlated with the Neuropsychological Assessment Battery Naming test, r=0.84, p<.01, Delis-Kaplan Executive Function System (D-KEFS) Category Fluency, r=0.45, p<.01, and the D-KEFS Letter Fluency, r=0.40, p<.01. ROC analyses found the measure to have sensitivity of 79% and specificity of 85% for detecting dysnomia. Patients with dysnomia performed worse on the measure than patients with intact word-finding, t(84)=8.2, p<.001. Patients with no cognitive impairment performed significantly better than patients with mild cognitive impairment, who performed significantly better than patients with dementia. This new measure shows promise in the neuropsychological evaluation of word-finding ability in older adults with or without visual impairment. Future directions include the development of a shorter version and the generation of additional normative data.


Subject(s)
Cognition Disorders/diagnosis , Executive Function/physiology , Names , Verbal Behavior/physiology , Adult , Aged , Aged, 80 and over , Female , Humans , Judgment/physiology , Logistic Models , Male , Middle Aged , Neuropsychological Tests , Psychometrics , ROC Curve , Verbal Learning/physiology , Veterans , Young Adult
20.
Biol Psychol ; 105: 20-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25559772

ABSTRACT

A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.


Subject(s)
Brain Injuries/complications , Brain/physiopathology , Depression/complications , Depressive Disorder/complications , Diffusion Tensor Imaging , Stress Disorders, Post-Traumatic/complications , White Matter/physiopathology , Adult , Afghan Campaign 2001- , Brain Injuries/physiopathology , Brain Injuries/psychology , Depression/physiopathology , Depression/psychology , Depressive Disorder/physiopathology , Depressive Disorder/psychology , Female , Humans , Iraq War, 2003-2011 , Male , Middle Aged , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology
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