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Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.
We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week.
The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement.
Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.
Since 2008 the Global Anglican Futures Conference (Gafcon) has emerged as a powerful force within the Anglican Communion. It had the potential to reform some of the issues facing the Anglican Communion. However, its Jerusalem Declaration has become a standard of Anglican orthodoxy to the exclusion of many orthodox Anglicans who cannot assent to its extra-doctrinal material. This lends Gafcon to schismatic ends.
This chapter situates Wright’s writings on the decolonizing world—especially White Man, Listen! and The Color Curtain —in the context of postcolonial thought. Beginning with his speech at the First International Conference of Negro Writers and Artists in Paris in 1956, it focuses on Wright’s relation to and divergence from the Négritude movement (Senghor, Césaire) as well as other traditions of postcolonial thought, such as the writings of Franz Fanon. It explores Wright’s efforts to develop a perspective from which to interpret the unprecedented historical force of decolonization, and it examines in particular how Wright sought to link—through the frame of modernity—his vantage point as a radical black intellectual in the United States with an emergent global postcolonial and anticolonial intellectual tradition.
To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA).
Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale – Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy).
The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains.
The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.
Patients with schizophrenia spectrum disorders have been increasingly recognised to form cognitive subgroups with differential levels of impairment. Using cluster analytical techniques, this study sought to identify cognitive clusters in a sample of first-episode psychosis (FEP) patients and examine clinical and developmental differences across the resultant groups.
In total, 105 FEP patients in the University of California Los Angeles Aftercare Research Program were assessed for cognition, symptoms and premorbid developmental adjustment. Hierarchical cluster analysis with Ward's method and squared Euclidean distance was conducted, confirmed by discriminant function analysis and optimised with k-means clustering. The stability of the solution was evaluated through split-sample (random, 80 and 70% samples) and alternate method (average linkage method) replication via Cohen's κ analysis. Controlling for multiple comparisons, one-way analysis of variances examined group differences in symptom severity and premorbid adjustment.
Three groups were identified: severely impaired (n = 27), moderately impaired (n = 41) and relatively intact (n = 37). There were no significant differences in symptom severity across the groups. Significant differences were observed for scholastic performance at three different developmental stages: childhood, early adolescence and late adolescence, with the relatively intact group demonstrating significantly better scholastic performance at all three stages than both the moderately impaired and severely impaired groups (who did not significantly differ from each other).
The findings add to growing evidence that cognitive clusters in FEP mirror that of later-stage schizophrenia. They also suggest that premorbid scholastic performance may not just be a risk factor for developing schizophrenia, but is also related to cognitive impairment severity and potentially to prognosis.
ABSTRACT IMPACT: Investigation of tumor-associated blood vessels may serve as an imaging biomarker of response to systemic therapy and cancer outcomes. OBJECTIVES/GOALS: Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC) and generate clinical utility. METHODS/STUDY POPULATION: During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). RESULTS/ANTICIPATED RESULTS: Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
This 68-year-old right-handed woman was evaluated for parkinsonism. Over the prior nine months, she had progressively become more withdrawn from her husband, whom she had been married to for 45 years. Initially, she would intermittently startle when her husband came into the room. Later, she started to sleep in a separate bed and avoided changing her clothes in front of him. When her husband asked her if there was anything wrong, she avoided him without any explanation. She progressively became verbally and physically aggressive toward him, which led to an intervention by her children. When they asked her if there were interpersonal issues between her and their father, she reported that he was not her husband. She acknowledged the resemblance but insisted that he was actually an impostor. Her children’s attempts to prove her wrong only made her more agitated. She was taken to the emergency room, where, after ruling out infections, toxic exposures, and stroke, she was given diagnosis of a psychotic disorder and was started on an antipsychotic, risperidone 2 mg daily. While this helped with her agitation, she became slower in her thinking. Her level of attention would fluctuate, and sometimes it appeared as if she were in a daze. In addition, a bilateral hand tremor emerged, and she started to shuffle.
Within the ever-evolving field of cognitive and behavioral neurology, management remains the most challenging aspect in clinical practice. These cases are a testament to changing paradigms of care and the importance of understanding the impact of certain treatments.
Brain imaging can be a very helpful tool in the diagnosis of cognitive and behavioral neurology. As with the clinical examination, it must be carefully interpreted. We present cases where subtle clues affected diagnosis.
This 65-year-old right-handed woman presented with a 2-year history of worsening gait and short-term memory impairment. She first noticed slowness in her movements and impaired balance resulting in falls, mostly backward. She tried levodopa titrated to 1200 mg a day with no benefit. Over the previous year, she developed difficulties multitasking and was easily distracted. She endorsed difficulty swallowing and, more recently, urinary incontinence. Her husband noted that she was withdrawn and seemed to have lost interest in hobbies and in social interactions with the family. She denied depression, anxiety, cognitive fluctuations, or hallucinations. She endorsed decreased sense of smell and a history of dream enactment behaviors. On neurological exam, she was easily distractible and tangential. Her speech was hypophonic. Her extraocular eye movements were normal. There was symmetric bradykinesia and distal hand myoclonus when the arms were held outstretched. She was unable to walk unaided (Video 23.1). The Montreal Cognitive Assessment (MoCA) score was 18/30, with impairments in trail making, cube copying, and clock drawing, backward digit span, serial sevens, sentence repetition and delayed recall (she recalled one word freely and recognized the other four when multiple choices were given).
This 51-year-old right-handed woman requested further care for her previously diagnosed Alzheimer disease. Over the previous year, her coworkers observed that she would frequently forget instructions and conversations and increasingly relied on written reminders. She would ask the same question repeatedly and cueing helped inconsistently. Her symptoms had not worsened since. There were no language or visuospatial impairments. Her past medical history included lumpectomy and tamoxifen for breast cancer five years ago, and a 30-year history of alcohol abuse (daily beer and vodka, unknown volume). Indeed, family members reported finding empty bottles of vodka in the garbage. She had no family history of cognitive impairment or other neurologic condition. Previous work up included a normal blood work, brain MRI with contrast, normal cell count, protein, glucose, and cytology in cerebrospinal fluid, but bilateral temporoparietal hypometabolism on FDG-PET (Figure 35.1). With a presumed diagnosis of Alzheimer disease, she was started on donepezil 5 mg daily.
This 69-year-old right-handed woman presented with 3-year history of progressive memory problems. Her husband described her initial difficulty was recalling recent events along with repeating stories. Within a year, she struggled with reading and with recognizing people, which she attributed to a change in vision. An ophthalmologic evaluation revealed bilateral cataracts, which were surgically corrected. However, her visual abilities continued to decline after surgery. She started having difficulties identifying objects and judging distances, which led her to stop driving. She denied any issues with her memory and attributed all of her problems to her vision, although she could not elaborate further. Her exam was remarkable for a circumlocutory discourse. Her Montreal Cognitive Assessment (MoCA) score was 12/30 due to impairments in trail making, cube copying, clock drawing, naming, serial sevens, phonemic fluency, delayed recall (she could not recall any words freely and recognized only one when multiple choices were given), and orientation to month and date.
This 60-year-old woman presented with a 6-year history of bilateral hand tremor and progressive gait impairment. She first noticed bilateral hand tremor when holding objects, followed by balance impairment, slow walking with foot dragging, and a tendency to fall forward. Within four years, she required a wheelchair for ambulation. She endorsed initial short-term memory affecting her ability to process information, which accelerated in the last year. Two years prior to the onset of her symptoms she had received chemotherapy (carboplatin and etoposide) with prophylactic whole-brain radiation as treatment for lung cancer.
This 65-year-old right-handed man presented with worsening “memory” problems for the past 5 years. He first noticed increasing difficulties with performing previously well-known and simple repairs at home, such as changing a light switch. A neuropsychological evaluation was reportedly normal. More recently, his family noticed declining skills in driving and use of appliances. In addition, performance of other tasks, such as preparing coffee, was affected by pauses and unnecessary steps. More recently, he was forgetful about recent events and unintentionally repetitive. There were no word-finding or navigation difficulties. On exam, he did not appear to be concerned about his impairments and inappropriately joked about them. His speech was fluent with occasional word-finding difficulties. He displayed optic ataxia and oculomotor apraxia, as well as simultanagnosia.
This 57-year-old right-handed woman presented to the clinic after four episodes of amnesia. The first one occurred six months previously while at her daughter’s house. Abruptly, she became disoriented to location and situation. She knew who she was and could recognize her daughter. She was reoriented by her daughter multiple times but still repeatedly asked where she was. She was taken to the emergency room, and after 45 minutes, she returned to her baseline and could recall the episode of disorientation. Her neurological exam was unremarkable, as well as her laboratory investigations, brain MRI, and EEG. She was discharged back home with the diagnosis of transient global amnesia (TGA). She had three additional episodes of similar characteristics since then, all within the last two months. She was on treatment with amlodipine for hypertension. Her repeat exam in the office setting was unremarkable.
This 76-year-old right-handed man with an amnestic presentation, suspicious for Alzheimer disease and diagnosed 5 years earlier, returned to the clinic for follow-up. Although he initially experienced improvement with donepezil, his cognition progressively declined over the following three years. In the last six months, his wife, who was his primary caregiver, noted that he was more forgetful and repetitive. However, now when he misplaced objects (e.g., wallet, books), he became convinced that the lost objects were stolen, even when the missing items were found and shown to him. Her repeated attempts to reassure him that the objects were merely misplaced triggered agitation and confusion. No threatened or real physical aggression ensued. In the office, he had no recollection of the events. He was oriented to place and person. His speech was fluent and his discourse was circumlocutory. The remainder of the exam was unremarkable.