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ObjectiveSubjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.MethodsFifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).ResultsHigher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.ConclusionsOur preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance.96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity.Moderate intensity PA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150 min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language.Encouraging MIPA, particularly the WHO recommendation of ≥150 min of MIPA/week, may represent an important prescription for PD cognition.

ObjectivesCare partners who provide informal care to individuals with Parkinson's disease (PD) report higher levels of burden and depression; however, longitudinal research on these symptoms is scarce. The current study assessed changes in care partner burden and depression, and patient and care partner predictors of these symptoms over time. Such knowledge may provide important information for assessment and treatment of depression and burden in care partners of individuals with PD.Research design and methodsParticipants were 88 PD patients without dementia and their self-identified care partner (n = 88). Care partners completed the Geriatric Depression Scale and Zarit Burden Interview. PD participants completed mood questionnaires and a motor exam at baseline and 2 year follow-up. Relationships among care partner burden and depression over time with patient and care partner predictors (i.e., demographic, mood, and disease characteristics) were assessed using correlations and regression analyses.ResultsCare partner burden and depression significantly increased over an approximate 2 year period. Greater baseline disease severity predicted worsening of care partner burden (p = 0.028), while baseline patient depression predicted worsening of care partner depression (p = 0.002).ConclusionsResults highlight differential impacts of specific PD symptoms on worsening care partner burden compared to depression; increased PD disease severity predicts increased burden, while patient mood predicts worsening of depression over time. Targeting PD disease severity and mood symptoms may prevent the progression of care partner burden and depression.

ObjectiveRapid Eye Movement Sleep Behavior Disorder (RBD) is common in Parkinson's Disease (PD) and is associated with cognitive impairment; however, the majority of the evidence on the impact of RBD on multidomain cognitive batteries in PD is cross-sectional. This study evaluated the longitudinal impact of probable RBD (pRBD) on cognitive, psychiatric, and functional outcomes in people with PD.MethodCase-control study. A total of 65 people with PD completed the study protocol at baseline and 16-to-47-month follow-up. Participants were classified as pRBD+ (n = 25) or pRBD- (n = 40) based on an established cutoff of 6 on the RBD Sleep Questionnaire (RBDSQ). Participants also completed a) comprehensive cognitive testing, b) self-report measures of depression, anxiety, and apathy, and c) performance-based and other-report forms of instrumental activities of daily living.ResultsBaseline mean age was 67.8 (SD = 8.1; range = 45-86) and baseline mean years of education was 16.4 (SD = 2.1; range = 12-20). The two groups did not differ on measured demographic characteristics. Baseline mean T-scores for cognitive tests were in the average range (46-55). Hierarchical linear models tested group differences in cognitive and functional decline from baseline to follow-up, controlling for appropriate demographic and psychiatric variables. Compared to the pRBD- group, pRBD+ participants showed greater decline in attention/working memory (r = -0.31; p = 0.01) and UPSA financial skills (r = -0.31; p = 0.01). No other group differences approached significance.ConclusionsRBD may differentially affect attention/working memory and financial abilities in PD. Results underscore the importance of regular RBD screening in older adults with PD in order to triage symptomatic patients to appropriate cognitive and medical interventions.

We examined the association between cognitive functioning and health-related quality of life (HR-QOL) in military veterans with a history of mild traumatic brain injury (mTBI) using two methods to assess cognition: mean performance on cognitive composite scores and across-test intraindividual variability (IIV). The sample included 73 veterans (84.9% male; age, mean = 32.47 years) who completed neuropsychological testing and self-report questionnaires ∼7 years post-injury. Three cognitive composite scores representing mean performance were computed, including memory, attention/processing speed (A/PS), and executive functioning (EF). Three IIV indices were also calculated reflecting degree of dispersion across the same cognitive domains: memory-IIV, A/PS-IIV, and EF-IIV. The Posttraumatic Stress Disorder (PTSD) Checklist-Military Version (PCL-M) was used to assess current PTSD symptoms, and the World Health Organization Quality of Life Short Version Physical Health domain was used to assess HR-QOL. Hierarchical linear regressions adjusting for PTSD symptoms demonstrated that IIV indices, but not mean cognitive composite scores, significantly predicted HR-QOL. Specifically, memory-IIV, A/PS-IIV, and EF-IIV, when taken together, made an independent and significant contribution to the prediction of HR-QOL. Examination of the standardized coefficients showed that the A/PS-IIV index was uniquely associated with HR-QOL, such that higher A/PS-IIV scores significantly predicted poorer HR-QOL. Our results are the first to show that, in veterans with remote mTBI histories, greater fluctuations in cognitive performance significantly contribute to poorer HR-QOL, even after accounting for PTSD symptom severity. Moreover, findings suggest that, compared to traditional mean cognitive performance scores, measures of IIV may represent more sensitive indicators of clinical outcome and better align with subjective experiences of distress.

ObjectiveFrontal behaviors (i.e., executive dysfunction, disinhibition, apathy) are common in Parkinson's disease (PD). However, it is unclear if patient and informant reports of patient frontal behaviors are in agreement over time.MethodSixty-two PD patients without dementia and their informants (87% spouses/partners) completed the self- and informant-versions of the Frontal Systems Behavior Scale at baseline and 2-year follow-up. Dyad ratings were compared and predictors of behavior ratings were examined.ResultsPatient and informant reports at baseline and follow-up were in agreement, with significant increases in overall frontal behaviors, executive dysfunction, and apathy. Higher levels of baseline patient depression and caregiver burden predicted decrements in patient-reported executive function; worse patient cognition at baseline predicted worsening apathy as rated by informants.ConclusionsPD patients and their informants are concordant in their ratings of worsening frontal behaviors over time. Targeting patient depression, cognition, and caregiver burden may improve decrements in frontal behaviors (executive dysfunction and apathy) in PD.

BackgroundPost-traumatic headache (PTH) is a commonly experienced symptom after mild traumatic brain injury (mTBI). Blast injury- or blunt injury-related mechanisms for mTBI in veterans can also affect musculoskeletal structures in the neck, resulting in comorbid neck pain (NP). However, it is unknown whether the presence of comorbid NP may be associated with a different pattern of headache symptoms, physical functioning, or emotional functioning compared to those without comorbid NP. The purpose of this study is to examine the role of comorbid NP in veterans with mTBI and PTH.Design and methodsThis was a cross-sectional investigation of an existing dataset that included 33 veterans who met inclusion criteria for PTH after mTBI. Standardized measures of headache severity and frequency, insomnia, fatigue, mood disorders, and physical and emotional role function were compared between groups with and without comorbid NP.ResultsThe majority of participants with PTH reported comorbid NP (n = 22/33, 67%). Those with comorbid NP experienced more headache symptoms that were severe or incapacitating, as compared to mild or moderate for those without NP (φ = 0.343, P = .049); however, no differences in headache frequency (φ = 0.231, P = .231) or duration (φ = 0.129, P = .712) were observed. Participants with comorbid NP also reported greater insomnia (d = 1.16, P = .003) and fatigue (d = 0.868, P = .040) as well as lower physical functioning (d = 0.802, P = .036) and greater bodily pain (d = 0.762, P = .012). There were no differences in anxiety, depression, mental health, emotional role limitations, vitality, or social functioning between those with and without comorbid NP (d ≤ 0.656, P ≥ .079).ConclusionsA majority of veterans with mTBI and PTH in our sample reported comorbid NP that was associated with greater headache symptom severity and physical limitations, but not with mood or emotional limitations. Preliminary findings from this small convenience sample indicate that routine assessment of comorbid NP and associated physical limitations should be considered in veterans with mTBI and PTH.

ObjectiveThe evaluation of memory complaints in mild traumatic brain injury (mTBI) remains an important clinical consideration, especially in the context of comorbid psychiatric symptoms such as posttraumatic stress disorder (PTSD). We compared subjective memory complaints in veterans with and without a history of mTBI, examined ratings between those with single versus multiple mTBIs, and investigated associations between memory complaints and PTSD symptom severity.Methods117 outpatient veterans (mTBI: n = 79 [single mTBI: n = 22, multiple mTBI: n = 57], military controls [MCs]: n = 38) completed a TBI history assessment, the Prospective-Retrospective Memory Questionnaire (PRMQ), and the PTSD Checklist-Military Version (PCL-M).ResultsHierarchical multiple regression showed that greater PCL-M scores significantly predicted elevated PRMQ-Total scores, accounting for 38% of the variance explained (P < .001). mTBI status predicted an additional 5% of variance in memory complaints (P < .01). The multiple-mTBI group endorsed more memory complaints than either MCs (P < .01) or the single-mTBI group (P < .05), who did not differ from MCs (P > .50).ConclusionsComorbid PTSD symptoms are an important factor when considering memory complaints in veterans with a reported history of mTBI. However, independent of comorbid PTSD symptoms, mTBI status-particularly in the context of repetitive neurotrauma-uniquely contributes to memory complaints. Findings suggest that veterans with a history of multiple mTBIs may be a particularly vulnerable group in need of specialized interventions and/or psychoeducation.

ObjectiveIndividuals with Parkinson's disease (PD) are at risk for increased medication mismanagement, which can lead to worse clinical outcomes. However, the nature of the errors (i.e., undertaking or overtaking medications) contributing to mismanagement and their relationship to cognition in PD is unknown. Therefore, this study sought to examine errors committed on the Medication Management Ability Assessment (MMAA) between PD participants with normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) relative to healthy adults (HA).MethodHA (n = 74), PD-NC (n = 102), and PD-MCI (n = 45) participants were administered the MMAA to assess undertaking, overtaking, and overall errors as well as overall performance (total score). Additionally, participants were administered a comprehensive neuropsychological battery from which cognitive composites of Attention, Learning, Memory, Language, Visuospatial, and Executive Functioning were derived.ResultsSeparate negative binomial regression analyses indicated the PD-MCI group performed significantly worse overall on the MMAA (total score) and committed more undertaking and overall errors relative to HA and PD-NC. In the PD-MCI group, poorer MMAA performance was associated with worse delayed memory performance, whereas cognitive performance was not related to MMAA in HA or PC-NC.ConclusionCompared to PD and healthy adults with normal cognition, PD-MCI patients exhibited greater difficulty with medication management, particularly with undertaking medications. Poorer medication management in PD-MCI was associated with worse delayed recall. Thus, PD-MCI patients experiencing memory problems may require additional assistance with their medications. Findings have clinical relevance suggesting that objective measures of medication errors may assist clinicians in identifying PD patients needing adherence strategies.

IntroductionAlthough subjective cognitive decline (SCD) may be an early risk marker of Alzheimer's Disease (AD), research on SCD among Hispanics/Latinos/as/x (henceforth Latinos/as) living in the U.S. is lacking. We investigated if the cross-sectional relationship of self-reported SCD with objective cognition varies as a function of ethnic background (Latinos/as versus Non-Hispanic Whites [NHWs]). Secondary analyses conducted solely within the Latino/a group investigated if informant reported SCD is associated with objective cognition and whether self-reported SCD is related to markers of brain health in a sub-sample of Latinos/as with available MRI data.MethodsEighty-three participants (≥60 years of age) without dementia (35 Latinos/as; 48 NHWs) completed the Mattis Dementia Rating Scale (MDRS) and the Subjective Cognitive Decline-Questionnaire (SCD-Q). Additionally, 22 Latino/a informants completed the informant-version of the SCD-Q. Hierarchical regression models investigated if ethnicity moderates the association of MDRS and SCD-Q scores after adjusting for demographics and depressive symptoms. Correlational analyses within the Latino/a group investigated self- and informant-reported associations of SCD-Q scores with objective cognition, and associations of self-reported SCD-Q scores with medial temporal lobe volume and thickness.ResultsLatinos/as had lower education and MDRS scores than NHWs. Higher SCD-Q scores were associated with lower MDRS scores only in Latinos/as. Within the Latino/a group, self, but not informant reported SCD was related to objective cognition. Medium to large effect sizes were found whereby higher self-reported SCD was associated with lower entorhinal cortex thickness and left hippocampal volume in Latinos/as.ConclusionsThe association of SCD and concurrent objectively measured global cognition varied by ethnic background and was only significant in Latinos/as. Self-reported SCD may be an indicator of cognitive and brain health in Latinos/as without dementia, prompting clinicians to monitor cognition. Future studies should explore if SCD predicts objective cognitive decline in diverse groups of Latinos/as living in the U.S.

ObjectiveThe utility of informant-based measures of cognitive decline to accurately describe objective cognitive performance in Parkinson's disease (PD) without dementia is uncertain. Due to the clinical relevance of this information, the purpose of this study was to examine the relationship between informant-based reports of patient cognitive decline via the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE) and objective cognition in non-demented PD controlling for cognitive status (i.e., mild cognitive impairment; PD-MCI and normal cognition; PD-NC).MethodOne-hundred and thirty-nine non-demented PD participants (PD-MCI n = 38; PD-NC n = 101) were administered measures of language, executive function, attention, learning, delayed recall, visuospatial function, mood, and motor function. Each participant identified an informant to complete the IQCODE and a mood questionnaire.ResultsGreater levels of informant-based responses of patient cognitive decline on the IQCODE were significantly associated with worse objective performance on measures of global cognition, attention, learning, delayed recall, and executive function in the overall sample, above and beyond covariates and cognitive status. However, the IQCODE was not significantly associated with language or visuospatial function.ConclusionsResults indicate that informant responses, as measured by the IQCODE, may provide adequate information on a wide range of cognitive abilities in non-demented PD, including those with MCI and normal cognition. Findings have important clinical implications for the utility of the IQCODE in the identification of PD patients in need of further evaluation, monitoring, and treatment.

ObjectiveWe examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms.MethodA total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA).ResultsAfter adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions.ConclusionsVeterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

BackgroundApathy is a prevalent, multidimensional neuropsychiatric condition in Parkinson's disease (PD). Several authors have proposed apathy subtypes in PD, but no study has examined the classification of PD patients into distinct apathy subtypes, nor has any study examined the clinical utility of doing so.ObjectivesThe current study used a data-driven approach to explore the existence and associated clinical characteristics of apathy subtypes in PD.MethodThe Apathy Scale (AS) was administered to 157 non-demented individuals with PD. Participants were classified into apathy subgroups through cluster analysis. Differences among apathy subtypes on external clinical indicators were explored across apathy subgroups.ResultsIndividuals with PD were classified into three subgroups: a Non-Apathetic group with low levels of apathy symptoms, a Low Interest/Energy group, characterized by elevated symptoms of low interest/energy and minimal low initiation/emotional indifference symptoms, and a Low Initiation group, characterized by an absence of low interest/energy symptoms and elevated levels of low initiation/emotional indifference symptoms. Both Low Interest/Energy and Low Initiation groups exhibited worse depression, fatigue, anxiety, health-related quality of life, and caregiver burden than the Non-Apathetic subgroup. The Low Initiation group exhibited worse overall cognition, emotional well-being, state anxiety, communicative ability, and functional ability than the Low Interest/Energy group. Importantly, disease-related characteristics did not differ across apathy symptom subgroups.ConclusionsNon-demented PD patients can be separated into distinct apathy symptom subgroups, which are differentially associated with important clinical variables. Apathy subgroup membership may reflect disruption to different neural systems independent of disease progression.

Emerging evidence suggests mild traumatic brain injury related headache (MTBI-HA) is a form of neuropathic pain state. Previous supraspinal mechanistic studies indicate patients with MTBI-HA demonstrate a dissociative state with diminished levels of supraspinal prefrontal pain modulatory functions and enhanced supraspinal sensory response to pain in comparison to healthy controls. However, the relationship between supraspinal pain modulatory functional deficit and severity of MTBI-HA is largely unknown. Understanding this relationship may provide enhanced levels of insight about MTBI-HA and facilitate the development of treatments. This study assessed pain related supraspinal resting states among MTBI-HA patients with various headache intensity phenotypes with comparisons to controls via functional magnetic resonance imaging (fMRI). Resting state fMRI data was analyzed with self-organizing-group-independent-component-analysis in three MTBI-HA intensity groups (mild, moderate, and severe) and one control group (n = 16 per group) within a pre-defined supraspinal pain network based on prior studies. In the mild-headache group, significant increases in supraspinal function were observed in the right premotor cortex (T = 3.53, p

ObjectiveFrontal behaviors (i.e., executive dysfunction, disinhibition, apathy) are common in Parkinson's disease (PD). However, it is unclear if patient and informant reports of patient frontal behaviors are in agreement over time.MethodSixty-two PD patients without dementia and their informants (87% spouses/partners) completed the self- and informant-versions of the Frontal Systems Behavior Scale at baseline and 2-year follow-up. Dyad ratings were compared and predictors of behavior ratings were examined.ResultsPatient and informant reports at baseline and follow-up were in agreement, with significant increases in overall frontal behaviors, executive dysfunction, and apathy. Higher levels of baseline patient depression and caregiver burden predicted decrements in patient-reported executive function; worse patient cognition at baseline predicted worsening apathy as rated by informants.ConclusionsPD patients and their informants are concordant in their ratings of worsening frontal behaviors over time. Targeting patient depression, cognition, and caregiver burden may improve decrements in frontal behaviors (executive dysfunction and apathy) in PD.

ObjectiveRapid eye movement sleep behavior disorder (RBD) affects 33-46% of patients with Parkinson's disease (PD) and may be a risk factor for neuropsychological and functional deficits. However, the role of RBD on neuropsychological functioning in PD has yet to be fully determined. We, therefore, examined differences in neurocognitive performance, functional capacity, and psychiatric symptoms among nondemented PD patients with probable RBD (PD/pRBD+) and without (PD/pRBD-), and healthy comparison participants (HC).MethodsTotally, 172 participants (58 PD/pRBD+; 65 PD/pRBD-; 49 HC) completed an RBD sleep questionnaire, psychiatric/clinical questionnaires, performance-based and self-reported functional capacity measures, and underwent a comprehensive neuropsychological battery assessing attention/working memory, language, visuospatial function, verbal and visual learning and memory, and executive function.ResultsControlling for psychiatric symptom severity, the PD/pRBD+ group had poorer executive functioning and learning performance than the PD/pRBD- group and poorer neuropsychological functioning across all individual cognitive domains than the HCs. In contrast, PD/pRBD- patients had significantly lower scores than HCs only in the language domain. Moreover, PD/pRBD+ patients demonstrated significantly poorer medication management skills compared to HCs. Both PD groups reported greater depressive and anxiety severity compared to HCs; PD/pRBD+ group also endorsed greater severity of apathy compared to HCs.ConclusionsThe presence of pRBD is associated with poorer neuropsychological functioning in PD such that PD patients with pRBD have poorer cognitive, functional, and emotional outcomes compared to HC participants and/or PD patients without pRBD. Our findings underscore the importance of RBD assessment for improved detection and treatment of neuropsychological deficits (e.g., targeted cognitive interventions).

ObjectiveSince neurocognitive functioning following mild traumatic brain injury (mTBI) may be influenced by genetic factors that mediate synaptic survival and repair, we examined the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) on cognition using a well-defined sample of military Veterans with and without a history of mTBI.MethodParticipants included 138 Veterans (mTBI = 75; military controls [MCs] = 63) who underwent neuropsychological testing, including completion of self-report measures assessing psychiatric distress, and BDNF genotyping. The mTBI group was tested roughly 66.7 months following their most recent mTBI. Veterans were divided into two groups-Met+ (Met/Met and Met/Val; n = 49) and Met- (Val/Val; n = 89) and compared on domain-specific cognitive composite scores representing memory, executive functioning, and visuospatial speed.ResultsANCOVAs adjusting for psychiatric distress, sex, years of education, and ethnicity/race revealed a significant group (mTBI vs. MC) by BDNF genotype (Met + vs. Met-) interaction for the memory (p = .024; ηp 2 = .039) and executive functioning (p = .010; ηp 2 = .050) composites, such that Met+ mTBI Veterans demonstrated better performance than Met- mTBI Veterans on the cognitive measures, whereas Met+ MCs demonstrated worse performance relative to Met- MCs on the cognitive measures. No significant interaction was observed for the visuospatial speed composite (p = .938; ηp 2

ObjectiveWe evaluated the influence of the APOE-ε4 allele on post-concussive symptoms in military Veterans with a remote history of mild traumatic brain injury (mTBI).MethodParticipants (N = 77) were administered neuropsychiatric measures, on average, approximately 5 years following their most recent mTBI and provided a DNA sample for APOE genotyping. Veterans were divided into two groups based on their ε4 status (n = 14 ε4+, n = 63 ε4-). The Neurobehavioral Symptom Inventory (NSI) was the primary outcome measure, from which a total score was derived, as well as three symptom clusters (somatic, cognitive, and affective).ResultsANCOVAs showed a significant main effect of ε4 genotype on the NSI total score and somatic symptom cluster after adjusting for posttraumatic stress symptoms and mTBI history (p = .019-.028, ηp2 = .064-.073), such that ε4+ Veterans endorsed significantly greater symptoms than ε4- Veterans.ConclusionsOur findings suggest that genetic risk may help to explain the poorer long-term outcomes often observed in this population.

BackgroundThe Apathy Scale (AS), a popular measure of apathy in Parkinson's disease (PD), has been somewhat limited for failing to characterize dimensions of apathy, such as those involving cognitive, behavioral, and emotional apathy symptoms. This study sought to determine whether factors consistent with these apathy dimensions in PD could be identified on the AS, examine the associations between these factors and disease-related characteristics, and compare PD patients and healthy control (HCs) on identified factors.MethodsConfirmatory (CFA) and exploratory factor analysis (EFA) were conducted on AS scores of 157 nondemented PD patients to identify AS factors. These factors were then correlated with important disease-related characteristics, and PD and HC participants were compared across these factors.ResultsPreviously proposed AS models failed to achieve an adequate fit in CFA. A subsequent EFA revealed two factors on the AS reflecting joint cognitive-behavioral aspects of apathy (Motivation-Interest-Energy) and emotional apathy symptoms (Indifference). Both factors were associated with anxiety, depression, health-related quality of life, and independent activities of daily living, with Indifference associated more with the latter. In addition, only the Indifference factor was associated with cognitive functioning. PD patients reported higher levels of symptoms than HCs on both factors, with the group difference slightly larger on the Motivation-Interest-Energy factor.ConclusionThe AS can be decomposed into two factors reflecting Motivation-Interest-Energy and Indifference symptoms. These factors are differentially associated with clinical variables, including cognition and independent activities of daily living, indicating the importance of evaluating apathy from a multidimensional perspective.

Objective/backgroundThe Insomnia Severity Index (ISI) is a widely used self-report measure of insomnia symptoms. However, to date this measure has not been validated or well-characterized in veterans who have experienced traumatic brain injury (TBI). This study assessed the psychometric properties and convergent, divergent, construct, and discriminate validity of the ISI in veterans with a history of TBI.ParticipantsEighty-three veterans with history of TBI were seen in the VA San Diego Healthcare System as part of a research protocol.MethodsMeasures included the ISI, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Neurobehavioral Symptom Inventory, Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version.ResultsThe ISI demonstrated moderate to strong or excellent convergent and divergent validity. A principal component analysis indicated a single construct with excellent internal consistency (Cronbach's alpha = 0.92). In exploratory analyses, the ISI discriminated well between those with (73%) and without (27%) sleep disturbance based on the PSQI.ConclusionsResults from this study indicate validity of the ISI in assessing insomnia in veterans with history of TBI and suggest a cutoff score not dissimilar from non-TBI populations. Findings from this study can help inform clinical applicability of the ISI, as well as future studies of insomnia in TBI.

The Geriatric Depression Scale (GDS) is recommended for screening depression in individuals with Parkinson's disease (PD). Empirical evidence, however, is limited regarding its validity and factor structure in PD. Thus, the current study sought to evaluate the convergent and divergent validity of the GDS, as well as the structure and validity of the derived factors.MethodNondemented individuals with PD (n = 158) completed the GDS-30, and items were subjected to a principle component analysis. Geriatric Depression Scale total and factor scores were correlated with depression items from the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRSd) and Hamilton Rating Scale for Depression (HAMDd), as well as with the Apathy Scale (AS), State-Trait Anxiety Inventory (STAI), Modified Fatigue Impact Scale (MFIS), Parkinson's disease Sleep Scale, and a Subjective Cognitive Function composite score.ResultsThe GDS total score was strongly correlated with divergent neuropsychiatric measures (AS, r = 0.57; STAI, r = 0.66; MFIS, r = 0.60), while only moderately correlated with convergent measures (MDS-UPDRSd, r = 0.36; HAMDd, r = 0.32; Ps

OBJECTIVE:Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus-a structure vulnerable to both primary and secondary injuries in TBI-is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI. METHODS:Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses. RESULTS:Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10). CONCLUSIONS:Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

As few studies have examined the relationship between the apolipoprotein E (APOE) gene and clinical outcomes after military-related traumatic brain injury (TBI), we aimed to determine whether the ε4 allele of the APOE gene influences neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI. Participants included 133 veterans (TBI = 79; military controls [MC] = 54) who underwent APOE genotyping and were divided into ε4+ (TBI = 18; MC = 15) and ε4- (TBI = 61; MC = 39) groups. All participants underwent evaluation of psychological distress using the Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version. Two-way analyses of variance were conducted to examine the effect of group (TBI vs. MC) and APOE-ε4 status (ε4+ vs. ε4-) across symptom measures. There was a significant main effect of group across all symptom measures (TBI > MC; all p values

ObjectiveWe examined BOLD (Blood-Oxygen-Level Dependent) activity reduction upon stimuli repetition of face-name pairs in older adults with amnestic (aMCI) and non-amnestic (naMCI) mild cognitive impairment diagnosed using a comprehensive actuarial method, and relationships between activity reduction and behavioral indices.MethodTwenty-nine cognitively healthy older adults (CHs) and 20 with MCI (n = 12 aMCI; n = 8 naMCI) underwent functional MRI event-related imaging, a comprehensive neuropsychological battery, and 1-year follow-up exam. During scanning, participants were shown face-name pairs 1-3 times and administered a post-scan recognition task.ResultsThe MCI group demonstrated less activity reduction upon repetition of face-name pairs within the MTL and other regions compared to CHs. Less activity reduction was associated with poorer Time 1 neuropsychological performance for the CH group and poorer post-scan recognition performance for the MCI group. Less activity reduction was related to poorer neuropsychological performance at Time 2 in the MCI group. Within MCIs, those with aMCI demonstrated less activity reduction upon repetition of face-name pairs than those with naMCI.ConclusionsDistinct patterns of brain activity were identified in the MCI group compared to CHs, and aMCI compared to naMCI. Activated regions were not restricted to traditional memory circuitry, implicating a wider network of regions involved in the encoding of associative tasks. Findings add support to the hypothesis that lack of reduced BOLD activity reflects "faulty adaptation" to repeated stimuli and that reduction in activity represents successful encoding processes. They also provide further support for use of the face-name paradigm as a marker of prodromal Alzheimer's disease, and method to distinguish between MCI subtypes.

Objective: Blast exposure (BE) and mild traumatic brain injury (mTBI) have been independently linked to pathological brain changes. However, the combined effects of BE and mTBI on brain structure have yet to be characterized. Therefore, we investigated whether regional differences in cortical thickness exist between mTBI Veterans with and without BE while on deployment. We also examined whether cortical thickness (CT) and cognitive performance differed among mTBI Veterans with low vs. high levels of cumulative BE. Methods: 80 Veterans with mTBI underwent neuroimaging and completed neuropsychological testing and self-report symptom rating scales. Analyses of covariance (ANCOVA) were used to compare blast-exposed Veterans (mTBI+BE, n = 51) to those without BE (mTBI-BE, n = 29) on CT of frontal and temporal a priori regions of interest (ROIs). Next, multiple regression analyses were used to examine whether CT and performance on an executive functions composite differed among mTBI Veterans with low (mTBI+BE Low, n = 22) vs. high (mTBI+BE High, n = 26) levels of cumulative BE. Results: Adjusting for age, numer of TBIs, and PTSD symptoms, the mTBI+BE group showed significant cortical thinning in frontal regions (i.e., left orbitofrontal cortex [p = 0.045], left middle frontal gyrus [p = 0.023], and right inferior frontal gyrus [p = 0.034]) compared to the mTBI-BE group. No significant group differences in CT were observed for temporal regions (p's > 0.05). Multiple regression analyses revealed a significant cumulative BE × CT interaction for the left orbitofrontal cortex (p = 0.001) and left middle frontal gyrus (p = 0.020); reduced CT was associated with worse cognitive performance in the mTBI+BE High group but not the mTBI+BE Low group. Conclusions: Findings show that Veterans with mTBI and BE may be at risk for cortical thinning post-deployment. Moreover, our results demonstrate that reductions in CT are associated with worse executive functioning among Veterans with high levels of cumulative BE. Future longitudinal studies are needed to determine whether BE exacerbates mTBI-related cortical thinning or independently negatively influences gray matter structure.

BackgroundVisual Hallucinations (VH) are a common symptom experienced by individuals with Parkinson's disease (PD); however, a validated measure of VH has yet to be established for this population. The North-East Visual Hallucinations Interview (NEVHI), a promising VH measure, has not been well validated in PD. The aim of this study was to evaluate the convergent and discriminant validity of the NEVHI as well as the proportional identification and characteristics of VH in PD.MethodsOne hundred seventeen individuals with PD completed the NEVHI as well as evaluations of psychological, cognitive, motor, and visual functioning as measures of convergent and divergent validity. The hallucination items from the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess convergent validity.ResultsThe NEVHI identified 20.5% of PD patients with VH, which consisted of all individuals detected by the MDS-UPDRS and NPI and nine additional individuals not detected by the other measures. The NEVHI was strongly correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the NPI VH item. Weak to non-significant correlations were found between the NEVHI and measures of psychological, cognitive, motor, visual, and demographic characteristics.DiscussionThe NEVHI identified a greater number of individuals with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent validity between the NEVHI and a clinician-administered-to-patient-report measure of VH and excellent divergent validity, supporting the NEVHI as a valid and preferable measure for assessing the presence of VH in PD.

Given the demand for developing objective methods for characterizing traumatic brain injury (TBI), research dedicated to evaluating putative biomarkers has burgeoned over the past decade. Since it is critical to elucidate the underlying pathological processes that underlie the higher diverse outcomes that follow neurotrauma, considerable efforts have been aimed at identifying biomarkers of both the acute- and chronic-phase TBI. Such information is not only critical for helping to elucidate the pathological changes that lead to poor long-term outcomes following TBI but it may also assist in the identification of possible prevention and interventions for individuals who sustain head trauma. In the current review, we discuss the potential role of vascular dysfunction and chronic inflammation in both acute- and chronic-phase TBI, and we also highlight existing studies that have investigated inflammation biomarkers associated with poorer injury outcome.

ObjectiveTo identify key mood, social, and functional correlates of current participation in mental health treatment and barriers to participation in mental health treatment among older HIV infected (HIV+) veterans.MethodsHIV+ veterans (N = 150) aged ≥ 50 years receiving HIV-related medical care at the VA San Diego Healthcare System, San Diego, California, anonymously completed a survey assessing current self-reported mood, social support, daily functioning problems, mental health service utilization, and barriers to participating in mental health services. Veterans also completed the 2-item Patient Health Questionnaire (PHQ-2), a validated depression screening instrument frequently used in primary care settings. Data were collected from February 2014 to May 2014.ResultsOverall, 44% of participants screened positive for depressive symptomatology on the PHQ-2; 55% of those who screened positive were participating in mental health treatment. Of the 45% of veterans who screened positive on the PHQ-2 and were not in treatment, two-thirds (66%) stated they had been offered services; however, they were not engaging in or accepting the services. Regardless of PHQ-2 status, current self-reported depressive symptoms emerged as an independent, significant positive predictor of participation in mental health treatment (odds ratio = 5.98; 95% CI, 1.16-30.72; P = .03), whereas anxiety, HIV-related stigma, sufficiency of social support, and daily functioning problems were not associated with mental health treatment utilization. Primary reported barriers to mental health treatment included scheduling/availability, travel time and transportation, and discomfort with group settings.ConclusionsResults of this study suggest there may be a need to better engage older HIV+ veterans in depression-related treatment. The use of telehealth technology, such as teletherapy, electronic devices, and cell phone-based programs, may be beneficial in helping older HIV+ veterans overcome many barriers that restrict their participation in mental health treatment.

ObjectiveCerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI.Methods37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI.ResultsRegression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p

ObjectiveGiven the increase in hoarding symptoms with age, there is a pressing need for understanding the clinical features as they relate to potential interventions for older adults with hoarding disorder (HD). The aim of the current investigation was to explore age-related differences in the level of functional and cognitive impairment in individuals with HD.MethodsThe current study utilized the baseline assessments of 122 adults with HD. Age-related differences in the raw scores of psychiatric, cognitive, and daily functioning were analyzed using a series of multiple regression models controlling for the possible age-related differences in premorbid IQ.ResultsOur results suggested that older adults with HD may experience increased levels of impairment in skills related to executive functioning and everyday functioning when compared with younger adults with HD.ConclusionsGiven these difficulties with neurocognitive functioning, older HD patients may require interventions that focus more on behavioral and functional skills, rather than focusing on changing thought processes. Copyright © 2016 John Wiley & Sons, Ltd.

ObjectiveFailure on performance validity tests (PVTs) is common in Veterans with histories of mild traumatic brain injury (mTBI), leading to questionable validity of clinical presentations.ParticipantsUsing diffusion tensor imaging, we investigated white matter (WM) integrity and cognition in 79 Veterans with history of mTBI who passed PVTs (n = 43; traumatic brain injury [TBI]-passed), history of mTBI who failed at least 1 PVT (n = 13; TBI-failed), and military controls (n = 23; MCs) with no history of TBI.ResultsThe TBI-failed group demonstrated significantly lower cognitive scores relative to MCs and the TBI-passed group; however, no such differences were observed between MCs and the TBI-passed group. On a global measure of WM integrity (ie, WM burden), the TBI-failed group showed more overall WM abnormalities than the other groups. However, no differences were observed between the MCs and TBI-passed group on WM burden. Interestingly, regional WM analyses revealed abnormalities in the anterior internal capsule and cingulum of both TBI subgroups relative to MCs. Moreover, compared with the TBI-passed group, the TBI-failed group demonstrated significantly decreased WM integrity in the corpus callosum.ConclusionsFindings revealed that, within our sample, WM abnormalities are evident in those who fail PVTs. This study adds to the burgeoning PVT literature by suggesting that poor PVT performance does not negate the possibility of underlying WM abnormalities in military personnel with history of mTBI.

ObjectiveTo investigate white matter microstructure compromise in Veterans with a history of traumatic brain injury (TBI) and its possible contribution to posttraumatic stress disorder (PTSD) symptomatology and neuropsychological functioning via diffusion tensor imaging.Participants and methodsThirty-eight Veterans with mild (n = 33) and moderate (n = 5) TBI and 17 military control participants without TBI completed neuropsychological testing and psychiatric screening and underwent magnetic resonance imaging an average of 4 years following their TBI event(s). Fractional anisotropy (FA) and diffusivity measures were extracted from 9 white matter tracts.ResultsCompared with military control participants, TBI participants reported higher levels of PTSD symptoms and performed worse on measures of memory and psychomotor-processing speed. Traumatic brain injury was associated with lower FA in the genu of the corpus callosum and left cingulum bundle. Fractional anisotropy negatively correlated with processing speed and/or executive functions in 7 of the 8 tracts. Regional FA did not correlate with memory or PTSD symptom ratings.ConclusionResults suggest that current PTSD symptoms are independent of TBI-related white matter alterations, as measured by diffusion tensor imaging. In addition, white matter microstructural compromise may contribute to reduced processing speed in our sample of participants with history of neurotrauma. Findings of the current study add insight into the factors associated with complicated recovery from mild to moderate TBI.

ObjectivesThe current investigation utilized mid-life and late-life participants diagnosed with hoarding disorder (HD) to explore the relationship between executive functioning and hoarding severity.DesignCorrelational analyses were used to investigate the associations between executive functioning and hoarding severity in nondemented participants. Multiple regression was used to determine if executive functioning had a unique association with HD severity when accounting for depressive symptoms.SettingParticipants were recruited from the San Diego area for HD intervention studies.ParticipantsParticipants were 113 nondemented adults aged 50-86 years who met DSM-5 criteria for HD. The mean age of the sample utilized in the analyses was 63.76 years (SD, 7.2; range, 51-85 years). The sample was mostly female (72%), Caucasian (81.4%), and unmarried (78%).MeasurementsHoarding severity was assessed using the Saving Inventory-Revised and the Clutter Image Rating and depression was assessed using the Hospital Anxiety and Depression Scale. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST-128) and the Trail Making and Verbal Fluency subtests of the Delis-Kaplan Executive Function System.ResultsExecutive function (operationalized as perseveration on the WCST-128) was significantly associated with Clutter Image Ratings. In a multivariate context, executive function and depressive symptom severity were both significant predictors of variance in Clutter Image Rating.ConclusionsOur results suggest that executive function is related to severity of HD symptoms and should be considered as part of the conceptualization of HD.

Comorbidity of posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI) is high among Veterans of Operation Iraqi Freedom/Enduring Freedom/New Dawn (OIF/OEF/OND). Cognitive processing therapy (CPT) is empirically supported for the treatment of PTSD, but it is not specifically designed to accommodate the memory, attention, or problem solving deficits that are experienced by many Veterans with comorbid PTSD and TBI. Compensatory cognitive rehabilitation, including cognitive symptom management and rehabilitation therapy (CogSMART), is effective for cognitive deficits stemming from a variety of etiologies, including TBI. We have integrated components of CogSMART into CPT in order to address the unique challenges faced by Veterans with ongoing cognitive complaints related to PTSD and a history of mild TBI. Here we describe an ongoing randomized controlled trial investigating the efficacy of our novel hybrid treatment, SMART-CPT, as compared to standard CPT, for OIF/OEF/OND Veterans with PTSD and a history of mild to moderate TBI. We describe the development of this hybrid treatment as well as implementation of the randomized controlled trial.

IntroductionClinical neuropsychological presentation of treatment-seeking Veterans with a remote history of mild traumatic brain injury (mTBI) is widely variable. This manuscript seeks to better characterize cognitive concerns in the post-acute phase following mTBI and to identify the neuropsychological profiles of a large sample of clinically referred Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans with a history of mTBI and current cognitive complaints. We hypothesized that a minority of cases would exhibit valid and widespread neuropsychological deficits.MethodRetrospective chart reviews of neuropsychological testing and mental health symptoms and diagnoses were conducted on 411 clinically referred OEF/OIF/OND Veterans with a history of mTBI. Groups were created based on scores on performance validity measures and based on overall neuropsychological performance.ResultsA total of 29.9% of the sample performed below normative expectations on at least one performance validity test (PVT). Of those Veterans performing adequately on PVTs, 60% performed within normal limits on virtually all neuropsychological measures administered, leaving only 40% performing below expectations on two or more measures. Mood and neurobehavioral symptoms were significantly elevated in Veterans performing below cutoff on PVTs compared to Veterans who performed within normative expectations or those with valid deficits. Neurobehavioral symptoms were significantly correlated with mental health symptom reports but not with injury variables.ConclusionsIn summary, in a large sample of clinically referred Veterans with persistent cognitive complaints after mild TBI, a third demonstrated invalid clinical neuropsychological testing, and, of those performing at or above cutoff on PVTs, over half performed within normative expectations across most neuropsychological tests administered. Results highlight the importance of objective assessment of cognitive functioning in this population as subjective reports do not correspond to objective assessment in the majority of cases.

ObjectiveWe investigated using diffusion tensor imaging (DTI) and the association between white matter integrity and executive function (EF) performance in postacute mild traumatic brain injury (mTBI). In addition, we examined whether injury severity, as measured by loss of consciousness (LOC) versus alterations in consciousness (AOC), is related to white matter microstructural alterations and neuropsychological outcome.ParticipantsThirty Iraq and Afghanistan War era veterans with a history of mTBI and 15 healthy veteran control participants.ResultsThere were no significant overall group differences between control and mTBI participants on DTI measures. However, a subgroup of mTBI participants with EF decrements (n = 13) demonstrated significantly decreased fractional anisotropy of prefrontal white matter, corpus callosum, and cingulum bundle structures compared with mTBI participants without EF decrements (n = 17) and control participants. Participants having mTBI with LOC were more likely to evidence reduced EF performances and disrupted ventral prefrontal white matter integrity when compared with either mTBI participants without LOC or control participants.ConclusionsFindings suggest that altered white matter integrity contributes to reduced EF in subgroups of veterans with a history of mTBI and that LOC may be a risk factor for reduced EF as well as associated changes to ventral prefrontal white matter.