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IntroductionThe effect of bilingualism on age at onset has yet to be examined within different clinical variants of Alzheimer's disease.MethodsWe reviewed the research charts of 287 well-characterized participants with either amnestic Alzheimer's dementia or logopenic variant primary progressive aphasia (lvPPA) and identified bilingual speakers based on regular use of two or more languages and/or ability to communicate with native speakers in two or more languages. We evaluated whether bilingual speakers demonstrated a delay in age of symptom onset relative to monolingual speakers while controlling for other variables known to influence cognitive reserve.ResultsA 5-year delay in age at symptom onset was observed for bilingual relative to monolingual speakers with lvPPA. This delay in onset was not observed in the amnestic Alzheimer's dementia cohort.DiscussionBilingualism may serve as a unique cognitive reserve variable in lvPPA, but not in amnestic Alzheimer's dementia.

BackgroundA personalized mobile health intervention (iSTEP) aims to promote a Mediterranean diet and increase physical activity, thereby improving neurocognitive functioning among persons living with HIV (PLWH). This article describes a qualitative study conducted to develop iSTEP for PLWH, including assessment of diet habits and preferences for tracking physical activity.MethodTwo focus groups, with seven and 13 PLWH respectively, discussed barriers and facilitators of a healthy diet and provided feedback to refine iSTEP components, including the feasibility of using a Fitbit and the content of text messages designed to encourage improved diet and physical activity.ResultsFocus group discussions revealed several healthy diet barriers, including housing instability, time required for food preparation, cost of healthy food, depression, gastrointestinal issues, physical disability, and changes in appetite since HIV diagnosis. Participant-identified healthy diet facilitators included affordable price options for healthy food, a structured food plan, desire to modify appearance or weight, access to medical professionals, motivation for disease prevention, and social support. Participants endorsed wearing a Fitbit on the wrist and receiving text messages as useful methods to monitor and encourage a better diet and greater physical activity.ConclusionsThese findings assisted the expansion of a mobile health intervention that promotes health behaviors in order to improve neurocognitive outcomes among PLWH.Trial registrationNCT03123731 , prospectively registered on ClinicalTrials.gov, April 21, 2017.

IntroductionPrimary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of speech and language. A growing body of research supports the utility of speech and language intervention in individuals with PPA, although access to these services remains limited. One potential means of increasing treatment accessibility is the delivery of treatment via telemedicine. Evidence supports the use of teletherapy in stroke-induced aphasia, but research examining the application of teletherapy in PPA is limited. In the current study, a non-randomized group comparison design was used to evaluate the feasibility and utility of treatment delivered via teletherapy relative to treatment administered in person for individuals with PPA.MethodsTwo treatment protocols were administered as part of a larger study investigating treatment for speech and language deficits in PPA. Participants with semantic (n=10) and logopenic (n=11) PPA received lexical retrieval treatment and individuals with nonfluent/agrammatic PPA (n=10) received video-implemented script training for aphasia designed to promote speech production and fluency. Treatment was administered via teletherapy for approximately half of the participants receiving each intervention. Treatment outcomes and performance on standardized tests were assessed at pre-treatment and post-treatment, as well as 3, 6, and 12 months post-treatment.ResultsOverall, both treatment approaches resulted in significant gains for primary outcome measures. Critically, comparison of in-person and teletherapy groups revealed comparable outcomes. Generalization to untrained targets and tasks and maintenance of treatment-induced gains were also comparable for traditional vs teletherapy participants.ConclusionOverall, treatment outcomes were largely equivalent for individuals receiving treatment via teletherapy vs traditional, in-person delivery. Results support the application of teletherapy for administering restitutive interventions to individuals with mild-to-moderate PPA. Potential implications for using teletherapy in the treatment of cognitive-linguistic and motoric impairments in other disorders and suggestions for administering treatment via telemedicine are discussed.

Non-fluent/agrammatic primary progressive aphasia (nfvPPA) is caused by neurodegeneration within the left fronto-insular speech and language production network (SPN). Graph theory is a branch of mathematics that studies network architecture (topology) by quantifying features based on its elements (nodes and connections). This approach has been recently applied to neuroimaging data to explore the complex architecture of the brain connectome, though few studies have exploited this technique in PPA. Here, we used graph theory on functional MRI resting state data from a group of 20 nfvPPA patients and 20 matched controls to investigate topological changes in response to focal neurodegeneration. We hypothesized that changes in the network architecture would be specific to the affected SPN in nfvPPA, while preserved in the spared default mode network (DMN). Topological configuration was quantified by hub location and global network metrics. Our findings showed a less efficiently wired and less optimally clustered SPN, while no changes were detected in the DMN. The SPN in the nfvPPA group showed a loss of hubs in the left fronto-parietal-temporal area and new critical nodes in the anterior left inferior-frontal and right frontal regions. Behaviorally, speech production score and rule violation errors correlated with the strength of functional connectivity of the left (lost) and right (new) regions respectively. This study shows that focal neurodegeneration within the SPN in nfvPPA is associated with network-specific topological alterations, with the loss and gain of crucial hubs and decreased global efficiency that were better accounted for through functional rather than structural changes. These findings support the hypothesis of selective network vulnerability in nfvPPA and may offer biomarkers for future behavioral intervention.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.

PurposeThe early period after chronic kidney disease (CKD) patients transition to end-stage renal disease (ESRD) represents the highest mortality risk but is variable among different patient populations and clinical circumstances. We compared early mortality outcomes among a diverse CKD population that transitioned to ESRD.MethodsA retrospective cohort study (1/1/2002 through 12/31/2013) of CKD patients (age ≥ 18 years) who transitioned to peritoneal dialysis (PD), hemodialysis (HD) with arteriovenous fistula/grafts, and HD with catheters was performed. Multivariable Cox regression modeling was used to estimate 6-month all-cause mortality hazard ratios (HR) among the three treatment groups after adjustment for patient and clinical characteristics.ResultsAmong 5373 ESRD patients (62.7 years, 41.3% females, 37.5% Hispanics, 13.3% PD, 34.9% HD with fistula/graft, 51.8% HD with catheter), 551 (10.3%) died at 6 months. Mortality rates were highest immediately after transition (299 deaths per 1000 person-years in first month). Compared to PD patients, the 6-month mortality HR (95% CI) was 1.87 (1.06-3.30) in HD with fistula/graft patients and 3.77 (2.17-6.57) in HD with catheter patients. Inpatient transition (HR 1.32), acute kidney injury (HR 2.06), and an eGFR ≥ 15 vs 5-9 (HR 1.68) at transition were also associated with higher early mortality risk.ConclusionAmong a diverse CKD population who transitioned to ESRD, we observed considerable differences in early mortality risk among PD, HD with fistula/graft, and HD with catheter patients. The identification of patient-specific and clinical environmental factors related to high early mortality may provide insights for managing advanced stages of CKD and shared decision making.

Higher levels of physical activity (PA) have been linked to better neurocognitive functioning in many populations. The current study examines the longitudinal association between PA and neurocognitive functioning among HIV-infected and HIV-uninfected persons. Community-dwelling adults (N = 291) self-reported level of PA and completed a comprehensive neuropsychological battery at two to four study visits (Mean follow-up time = 2.6 years). Participants were divided into three PA groups: "No PA" (no PA at any visit), "consistent PA" (PA at ≥50% of visits), and "inconsistent PA" (PA

BACKGROUND:Cognitive deficits are common among individuals on haemodialysis (HD). The degree of dysfunction may shift over the course of the interdialytic interval. OBJECTIVES:To use ecological momentary assessment (EMA) to examine the relationship between the length of the interdialytic interval and reports of cognitive dysfunction. DESIGN:A quantitative study whereby each patient's cognitive functioning was measured during both short and long interdialytic intervals. PARTICIPANTS:Adults maintained on HD (Female n = 15, Male n = 11; MAge  = 42.7 ± 15.8 years) were drawn from a standalone HD unit within a large university medical centre. MEASUREMENTS:Tests of baseline neurocognitive functioning were undertaken (Mini-Mental Status Examination, Digit Span, California Verbal Learning Test, Benton Visual Retention Test, Trail-Making Test) and smartphone-based electronic diary reports of cognitive impairment were made around six times each day for one week. RESULTS:Cognitive function and aptitude in this sample, although low, did not reflect clinically-significant impairment, with a mean Mini-Mental Status Exam score of 25.7 ± 3.0. Diary reports of cognitive impairment were also minimal, with an overall mean rating of .22 out of 5. Contrary to expectations, cognitive impairment was significantly greater on the one-day interdialytic days than on Day 2 of the two-day interdialytic interval (β = .094, p = .017). CONCLUSIONS:Although cognitive impairment appears to be mild in stable, young patients with end stage renal disease, volumetric disruptions caused by HD may exacerbate such dysfunction.

ImportanceThe ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies.ObjectiveTo determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA).Design, setting, and participantsThis prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA.Main outcomes and measuresClinical, cognitive, neuroimaging, and pathology results.ResultsTwenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy.Conclusions and relevancePrimary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

BackgroundMethamphetamine (METH) use is a risk factor for the transmission of HIV. Each is associated with neurocognitive impairment and subsequent problems in everyday functioning, yet additive effects of HIV and METH are not consistently observed. This study used the UCSD Performance-Based Skills Assessment (UPSA-2) to assess whether METH use disorder and HIV together resulted in poorer functional outcome than either condition alone.MethodParticipants in the Translational Methamphetamine AIDS Research Center (TMARC) cohort were stratified based upon HIV infection and METH use disorder: HIV-/METH- (n=49), HIV-/METH+ (n=48), HIV+/METH- (n=37), and HIV+/METH+ (n=38). They were administered the UPSA-2 which measures abilities in six domains of everyday functioning. Main effects and interactions of HIV and METH were examined, as were relationships between UPSA-2 scores and disease characteristics.ResultsSignificant HIV-by-METH interactions were observed for the UPSA-2 total score and Comprehension/Planning and Financial subscales such that METH was associated with lower scores in HIV- participants but not HIV+ participants. METH was associated with lower scores on the Communications subscale. All three risk groups had lower scores than HIV-/METH- participants. Recency and frequency of METH use were associated with lower scores. Lower Medication Management scores were related to lower nadir CD4 counts.ConclusionsMETH use disorder and HIV each impair functional performance, but there is no additive effect when the two conditions occur together. The neurocognitive sequelae of combined HIV infection and METH use are complex and warrant further study, as do the potential effects of compensatory strategies and other factors.

ObjectiveThe Kidney Disease Outcome Quality Initiative and Fistula First Breakthrough Initiative call for the indiscriminate creation of arteriovenous fistulas (AVFs) over arteriovenous grafts (AVGs) without providing patient-specific criteria for vascular access selection. Although the U.S. AVF rate has increased dramatically, several reports have found that this singular focus on increasing AVFs has resulted in increased AVF nonmaturation/early failure and a high prevalence of catheter dependence. The objective of this study was to determine the appropriateness of vascular access procedures in clinical scenarios constructed with combinations of relevant factors potentially influencing outcomes.MethodsThe RAND/UCLA Appropriateness Method was used. Accordingly, a comprehensive literature search was performed and a synthesis of results compiled. The RAND/UCLA Appropriateness Method was applied to 2088 AVF and 1728 AVG clinical scenarios with varying patient characteristics. Eleven international vascular access experts rated the appropriateness of each scenario in two rounds. On the basis of the distribution of the panelists' scores, each scenario was determined to be appropriate, inappropriate, or indeterminate.ResultsPanelists achieved agreement in 2964 (77.7%) scenarios; 860 (41%) AVF and 588 (34%) AVG scenarios were scored appropriate, 686 (33%) AVF and 480 (28%) AVG scenarios were scored inappropriate, and 542 (26%) AVF and 660 (38%) AVG scenarios were indeterminate. Younger age, larger outflow vein diameter, normal or obese body mass index (vs morbidly obese), larger inflow artery diameter, and higher patient functional status were associated with appropriateness of AVF creation. Older age, dialysis dependence, and smaller vein size were associated with appropriateness of AVG creation. Gender, diabetes, and coronary artery disease were not associated with AVF or AVG appropriateness. Dialysis status was not associated with AVF appropriateness. Body mass index and functional status were not associated with AVG appropriateness. To simulate the surgeon's decision-making, scenarios were combined to create situations with the same patient characteristics and both AVF and AVG options for access. Of these 864 clinical situations, 311 (36%) were rated appropriate for AVG but inappropriate or indeterminate for AVF.ConclusionsThe results of this study indicate that patient-specific situations exist wherein AVG is as appropriate as or more appropriate than AVF. These results provide patient-specific recommendations for clinicians to optimize vascular access selection criteria, to standardize care, and to inform payers and policy. Indeterminate scenarios will guide future research.

ObjectiveTo characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification.MethodsExtensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms.ResultsA clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with transactive response DNA-binding protein (TDP) inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer disease (AD) pathology in 19% of cases. Each variant was associated with 1 typical pathology; 24 of 29 (83%) svPPA showed FTLD-TDP type C, 22 of 25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants.InterpretationEach PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo. Ann Neurol 2017;81:430-443.

Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network.

Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects. The syndrome-specific epicentre of the non-fluent/agrammatic variant of primary progressive aphasia was derived in a group of 10 mildly affected patients (clinical dementia rating equal to 0) using voxel-based morphometry. From this region, the inferior frontal gyrus (pars opercularis), we derived functional and structural connectivity maps in healthy controls (n = 30) using functional magnetic resonance imaging at rest and diffusion-weighted imaging tractography. Graph theory analysis was applied to derive functional network features. Atrophy progression was calculated using voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic patients. Correlation analyses were performed to compare volume changes in patients with connectivity measures of the healthy functional and structural speech/language network. The default mode network was used as a control network. From the epicentre, the healthy functional connectivity network included the left supplementary motor area and the prefrontal, inferior parietal and temporal regions, which were connected through the aslant, superior longitudinal and arcuate fasciculi. Longitudinal grey and white matter changes were found in the left language-related regions and in the right inferior frontal gyrus. Functional connectivity strength in the healthy speech/language network, but not in the default network, correlated with longitudinal grey matter changes in the non-fluent/agrammatic variant of primary progressive aphasia. Graph theoretical analysis of the speech/language network showed that regions with shorter functional paths to the epicentre exhibited greater longitudinal atrophy. The network contained three modules, including a left inferior frontal gyrus/supplementary motor area, which was most strongly connected with the epicentre. The aslant tract was the white matter pathway connecting these two regions and showed the most significant correlation between fractional anisotropy and white matter longitudinal atrophy changes. This study showed that the pattern of longitudinal atrophy progression in the non-fluent/agrammatic variant of primary progressive aphasia relates to the strength of connectivity in pre-determined functional and structural large-scale speech production networks. These findings support the hypothesis that the spread of neurodegeneration occurs by following specific anatomical and functional neuronal network architectures.

Semantic variant primary progressive aphasia (svPPA) typically presents with left-hemisphere predominant rostral temporal lobe (rTL) atrophy and the most significant complaints within the language domain. Less frequently, patients present with right-hemisphere predominant temporal atrophy coupled with marked impairments in processing of famous faces and emotions. Few studies have objectively compared these patient groups in both domains and therefore it is unclear to what extent the syndromes overlap. Clinically diagnosed svPPA patients were characterized as left- (n = 21) or right-predominant (n = 12) using imaging and compared along with 14 healthy controls. Regarding language, our primary focus was upon two hallmark features of svPPA; confrontation naming and surface dyslexia. Both groups exhibited naming deficits and surface dyslexia although the impairments were more severe in the left-predominant group. Familiarity judgments on famous faces and affect processing were more profoundly impaired in the right-predominant group. Our findings suggest that the two syndromes overlap significantly but that early cases at the tail ends of the continuum constitute a challenge for current clinical criteria. Correlational neuroimaging analyses implicated a mid portion of the left lateral temporal lobe in exception word reading impairments in line with proposals that this region is an interface between phonology and semantic knowledge.

ObjectiveStage B, asymptomatic heart failure (HF) presents a therapeutic window for attenuating disease progression and development of HF symptoms, and improving quality of life. Gratitude, the practice of appreciating positive life features, is highly related to quality of life, leading to development of promising clinical interventions. However, few gratitude studies have investigated objective measures of physical health; most relied on self-report measures. We conducted a pilot study in Stage B HF patients to examine whether gratitude journaling improved biomarkers related to HF prognosis.MethodsPatients (n = 70; mean [standard deviation] age = 66.2 [7.6] years) were randomized to an 8-week gratitude journaling intervention or treatment as usual. Baseline (T1) assessments included the six-item Gratitude Questionnaire, resting heart rate variability (HRV), and an inflammatory biomarker index. At T2 (midintervention), the six-item Gratitude Questionnaire was measured. At T3 (postintervention), T1 measures were repeated but also included a gratitude journaling task.ResultsThe gratitude intervention was associated with improved trait gratitude scores (F = 6.0, p = .017, η = 0.10), reduced inflammatory biomarker index score over time (F = 9.7, p = .004, η = 0.21), and increased parasympathetic HRV responses during the gratitude journaling task (F = 4.2, p = .036, η = 0.15), compared with treatment as usual. However, there were no resting preintervention to postintervention group differences in HRV (p values > .10).ConclusionsGratitude journaling may improve biomarkers related to HF morbidity, such as reduced inflammation; large-scale studies with active control conditions are needed to confirm these findings.Trial registrationClinicaltrials.govidentifier:NCT01615094.

We assessed the feasibility and acceptability of using text messages to monitor and encourage physical activity in the first 21 participants enrolled in an ongoing randomized controlled trial evaluating a 16-week Short Message Service/Multimedia Message Service (SMS/MMS) intervention (iSTEP) designed to increase moderate physical activity and improve neurocognition in persons with HIV-associated neurocognitive disorders (HAND; iSTEP, n = 11; control group, n = 10). Data were collected during the intervention and from interviews conducted at the 16-week postintervention visits. Text message response rates for both iSTEP and control participants were high (89% and 85%, respectively). Pedometer self-monitoring, step count goals, and milestone achievement texts were reported to facilitate physical activity. All iSTEP participants (100%) and 70% of control participants indicated that they would recommend the study to other people living with HIV. The results indicate that it is feasible to administer an SMS/MMS physical activity intervention to persons with HAND.

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature.

ImportanceWe provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy.ObjectiveTo characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up.Design, setting, and participantsA prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included.Main outcomes and measuresClinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally.ResultsPatient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms.Conclusions and relevanceIn patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imaging may be useful for differentiating underlying PSP from CBD pathology during life.

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.

A randomized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention (iSTEP) designed to increase physical activity (PA) and improve neurocognitive functioning among HIV-positive persons. This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population, including assessment of PA barriers and facilitators. Two focus groups, with 9 and 12 unique HIV-positive individuals, respectively, were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA. Group discussions revealed prominent PA barriers, including HIV symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and fatigue; significant PA facilitators included self-monitoring and family support. Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities. These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders.

We examined the association between physical activity (PA), neurocognitive impairment (NCI), and instrumental activities of daily living (IADLs) among older HIV+ persons. One hundred older HIV+ adults completed the International Physical Activity Questionnaire, a neurocognitive battery, and IADL scale. Higher levels of moderate PA were associated with lower odds of NCI (p = 0.01), even when covariates were modeled. The association between moderate PA and NCI was driven by executive function (p = 0.04). Higher levels of moderate PA were also associated with lower odds of IADL Dependence (p = 0.03), although this fell to a trend (p = 0.08) when including covariates. Follow-up analysis showed those with both NCI and IADL Dependence had lower moderate PA than those with neither (p = 0.03). While these cross-sectional findings suggest PA is associated with better neurocognitive and everyday functioning in older HIV+ adults, longitudinal studies utilizing objective PA methods are needed to evaluate directionality and mechanisms.

Methamphetamine (MA) dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA-) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p=0.32). This analysis revealed significantly elevated IIV among MA+ relative to MA- individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems.

Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n = 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n = 31) and wild-type (n = 28) mice) and acute (C57BL/6J mice (n = 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by high-reward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies.

Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions. All three PPA variants showed deficits in inflectional morphology, with the specific nature of the deficits dependent on the anatomical and linguistic features of each variant. Deficits in inflecting low-frequency irregular words were associated with semantic PPA, with lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting pseudowords were associated with non-fluent/agrammatic and logopenic variants, with phonological deficits, and with left frontal and parietal atrophy.

In primary progressive aphasia (PPA), speech and language difficulties are caused by neurodegeneration of specific brain networks. In the nonfluent/agrammatic variant (nfvPPA), motor speech and grammatical deficits are associated with atrophy in a left fronto-insular-striatal network previously implicated in speech production. In vivo dissection of the crossing white matter (WM) tracts within this "speech production network" is complex and has rarely been performed in health or in PPA. We hypothesized that damage to these tracts would be specific to nfvPPA and would correlate with differential aspects of the patients' fluency abilities. We prospectively studied 25 PPA and 21 healthy individuals who underwent extensive cognitive testing and 3 T MRI. Using residual bootstrap Q-ball probabilistic tractography on high angular resolution diffusion-weighted imaging (HARDI), we reconstructed pathways connecting posterior inferior frontal, inferior premotor, insula, supplementary motor area (SMA) complex, striatum, and standard ventral and dorsal language pathways. We extracted tract-specific diffusion tensor imaging (DTI) metrics to assess changes across PPA variants and perform brain-behavioral correlations. Significant WM changes in the left intrafrontal and frontostriatal pathways were found in nfvPPA, but not in the semantic or logopenic variants. Correlations between tract-specific DTI metrics with cognitive scores confirmed the specific involvement of this anterior-dorsal network in fluency and suggested a preferential role of a posterior premotor-SMA pathway in motor speech. This study shows that left WM pathways connecting the speech production network are selectively damaged in nfvPPA and suggests that different tracts within this system are involved in subcomponents of fluency. These findings emphasize the emerging role of diffusion imaging in the differential diagnosis of neurodegenerative diseases.

Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA; also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the ATLs is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA to determine which regions normally involved in syntactic processing are damaged in semantic PPA and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural MRI and fMRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that, in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, whereas anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the ATLs but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left ATL did show abnormal functionality in semantic PPA patients; however, this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the ATL in sentence processing is less likely to relate to syntactic structure-building and more likely to relate to higher-level processes such as combinatorial semantic processing.

Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of language-related learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (χ(2) = 15.17, P < 0.001) and (χ(2) = 11.51, P < 0.001) compared with semantic and non-fluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (χ(2) = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to early-onset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.

Neurocognitive impairment (NCI) remains prevalent in HIV infection. Randomized trials have shown that physical exercise improves NCI in non-HIV-infected adults, but data on HIV-infected populations are limited. Community-dwelling HIV-infected participants (n = 335) completed a comprehensive neurocognitive battery that was utilized to define both global and domain-specific NCI. Participants were divided into "exercise" (n = 83) and "no exercise" (n = 252) groups based on whether they self-reported engaging in any activity that increased heart rate in the last 72 h or not. We also measured and evaluated a series of potential confounding factors, including demographics, HIV disease characteristics, substance use and psychiatric comorbidities, and physical functioning. Lower rates of global NCI were observed among the exercise group (15.7 %) as compared to those in the no exercise group (31.0 %; p

ImportanceEpileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease.ObjectiveTo describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity.DesignRetrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco.PatientsWe studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7).Main outcomes and measuresClinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications.ResultsPatients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P

Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus.

The ability of pulsed Doppler echocardiography to identify patients with left ventricular systolic dysfunction was evaluated in 12 patients with dilated (congestive) cardiomyopathy. A range-gated, spectrum analyzer-based Doppler velocimeter was used to record blood flow velocity in the ascending aorta and main pulmonary artery. The following blood flow velocity parameters were measured or derived: peak flow velocity, acceleration time, average acceleration, deceleration time, average deceleration, ejection time, and aortic flow velocity integral. Doppler blood flow velocity data in the cardiomyopathy patients were compared to data from 20 normal subjects. Measurements from the ascending aorta revealed that peak aortic flow velocity discriminated between cardiomyopathy patients (mean 47 cm/sec, range 35 to 62) and normal subjects (mean 92 cm/sec, range 72 to 120) with no overlap in data (p less than 0.001). Aortic flow velocity integral was also able to separate the patients with dilated cardiomyopathy (mean 6.7 cm, range 3.5 to 9.1) from normal subjects (mean 15.7 cm, range 12.6 to 22.5) with no overlap in data (p less than 0.001). Although mean values for average aortic acceleration and aortic ejection time were also significantly different (both p less than 0.005), there was some overlap between the two groups. Pulmonary artery blood flow studies demonstrated significantly increased average acceleration, as well as decreased ejection time (both p less than 0.05), but no difference in average deceleration or peak flow velocity in cardiomyopathy patients compared to normals. Compared to pulmonary flow measurements, aortic Doppler flow velocity measurements allowed better separation of cardiomyopathy and normal groups.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the optimal time for recording left ventricular angiograms during atrial pacing stress tests, digital subtraction left ventriculograms were obtained using 12 ml of contrast material in 40 patients at rest and at peak pacing. Nineteen of the 40 patients had a third digital left ventriculogram performed between 5 and 10 seconds and 21 patients had a third digital left ventriculogram performed 30 seconds after pacing was stopped. Coronary angiography showed significant coronary artery disease (CAD) in 29 patients and no evidence of significant CAD in 11 patients. Ejection fraction (EF) increased or did not change at peak pacing in 10 of 11 patients without CAD. In the 29 patients with CAD, mean EF decreased an average of 10 percentage points (p less than 0.001) and fell 2 or more percentage points in 25 patients (86%) at peak pacing. These changes in EF were accompanied by the development of wall motion abnormalities, which occurred in segments of myocardium that were supplied by coronary arteries with angiographic CAD (more than 50% diameter narrowing). In contrast, the mean EF during the postpacing studies decreased only 2.2 percentage points (difference not significant) over rest values. Moreover, 15 of 29 patients (52%) with CAD had a decrease in EF of 2 or more percentage points. Therefore, the sensitivity of the atrial pacing stress test was diminished when the analysis was performed at 10 or 30 seconds after pacing. It is concluded that EF changes and wall motion abnormalities induced by atrial pacing are of short duration.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the ability to detect coronary artery narrowings from computer-acquired angiograms, a panel of 4 observers independently identified and measured focal coronary narrowings from digital subtraction angiograms and compared the results to those obtained from standard 35-mm cine film angiograms. Both cine and digital angiograms were obtained sequentially using selective intracoronary artery injection of standard amounts of iodinated contrast media. Digital images were obtained at 8 frames/s with a 512 X 512 X 8-bit pixel matrix. Modifications in the imaging chain for computer acquisition included a slower pulsed radiographic mode, a progressive scan camera, and initial storage of the images on an 80-megabyte digital hard disk. Postprocessing computer algorithms were used to enhance the unsubtracted digital images; these included single-frame, mask-mode subtraction, vessel boundary edge enhancement, and 4-fold pixel magnification. In 19 patient studies, 32 arteries were reduced more than 25% in diameter according to at least 1 of 4 observers on either the digital or cine film angiograms. There was no significant difference in the mean percent diameter narrowing for all the narrowings between the digital angiograms (53 +/- 31%) and the cineangiograms (52 +/- 31%). In addition, a 2-way analysis of variance yielded no significant difference between the amount of variability in the measurements between the cine film and the digital technique. This similar variability persisted when subsets of patients based on the degrees of stenosis were considered (e.g., only narrowings from 50 to 90% diameter reduction).(ABSTRACT TRUNCATED AT 250 WORDS)

Using digital subtraction angiography, left ventriculograms were obtained with 10 ml of iodinated contrast material in 21 patients both at rest and during atrial pacing. In 15 patients with significant coronary artery lesions (CAD) (greater than 50% diameter narrowing in at least 1 major artery), ejection fraction decreased during atrial pacing from a mean of 62 +/- 14% to 51 +/- 15% (p less than 0.001). In 14 (93%) of 15 patients, ejection fraction decreased or was unchanged during pacing. In 6 patients with chest pain but normal coronary arteries, ejection fraction increased from a mean of 66 +/- 9% at rest to 72 +/- 6% during atrial pacing (p less than 0.01). Ejection fraction increased by greater than or equal to 5% during pacing in 5 of 6 patients with normal coronary arteries. Patients with CAD also had an abnormal response in end-systolic volume during atrial pacing (50 +/- 31 ml at rest versus 47 +/- 24 ml during pacing) compared with patients with normal coronary arteries (46 +/- 16 ml at rest versus 26 +/- 9 ml during pacing; p less than 0.01). The digital ventriculograms demonstrated new or increased wall motion abnormalities during atrial pacing in 4 of 5 patients with CAD who had wall motion abnormalities at rest and in 8 of 10 patients with CAD who had normal wall motion at rest. Moreover, these wall motion abnormalities occurred in myocardial wall segments that were supplied by coronary arteries with significant lesions. Thus, because digital subtraction angiography allows multiple left ventriculograms to be obtained during routine cardiac catheterization, intervention studies such as atrial pacing can be used to obtain a functional assessment of the severity of coronary arterial lesions.

Left ventricular ejection fraction (LVEF) was calculated from 25 first-pass digital subtraction angiograms using a densitometric analysis. Digital subtraction angiograms are obtained in a computerized format; therefore, they can be readily analyzed with computer software to measure the density of the iodine signal within the image. The video signals from the image intensifier were logarithmically amplified so that there was a linear correlation between the video signal intensity and the depth of the iodine contrast material represented by that video signal. LVEF was also calculated by the area-length method from the same digital subtraction angiograms. There was close correlation between these two techniques (r = 0.94, standard error of the estimate = 5.04%). The videodensitometric EF technique is simple to perform, it correlates well with the standard area-length method, and is not dependent on geometric assumptions of LV geometry.

Left ventriculograms were obtained with the use of 10 ml of contrast media by passing fluoroscopic video images through a video image processor. The low concentration of dye in the left ventricle was enhanced by the technique of mask mode subtraction, and the images were postprocessed to increase visibility by manipulation of the gray scale and contrast levels. These digital subtraction angiograms were compared to standard cineangiograms by means of 40 ml of contrast media. Of 30 patients studied, six (20%) had runs of ventricular tachycardia during the cineangiogram and had to be excluded. In the remaining 24 patients, there was a good correlation between the two techniques for left ventricular end-diastolic volume (r = 0.77, end-systolic volume (r = 0.95), and ejection fraction (r = 0.97). Spatial resolution in the digital studies was adequate to appreciate wall motion abnormalities that were visualized on the cineangiograms. Left ventricular end-diastolic pressure (LVEDP) did not change after the 10 ml injection, but the mean LVEDP rose 6.0 mm Hg after the 40 ml cineangiograms (p less than 0.01). Digital subtraction angiography can be used to obtain left ventriculograms with one-fourth the amount of contrast media and one-fourth the x-ray exposure compared to standard cineangiograms. This technology will permit multiple left ventriculograms to be obtained which, in turn, will allow intervention studies to be performed in the catheterization laboratory.