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To examine the interaction between structural brain volume measures derived from a clinical magnetic resonance imaging (MRI) and occurrence of neuropsychiatric symptoms (NPS) in outpatient memory clinic patients.
Clinical and neuroimaging data were collected from the medical records of outpatient memory clinic patients who were seen by neurologists, geriatric neuropsychiatrists, and geriatricians. MRI scan acquisition was carried out on a 3 T Siemens Verio scanner at Johns Hopkins Bayview Medical Center. Image analyses used an automated multi-label atlas fusion method with a geriatric atlas inventory to generate 193 anatomical regions from which volumes were measured. Regions of interest were generated a priori based on previous literature review of NPS in dementia. Regional volumes for agitation, apathy, and delusions were carried forward in a linear regression analysis.
Seventy-two patients had clinical and usable neuroimaging data that were analyzed and grouped by Mini-Mental State Exam (MMSE). Neuropsychiatric Inventory Questionnaire (NPI-Q) agitation was inversely associated with rostral anterior cingulate cortex (ACC) bilaterally and left subcallosal ACC volumes in the moderate severity group. Delusions were positively associated with left ACC volumes in both severe and mild groups but inversely associated with the right dorsolateral prefrontal cortex (DLPFC) in the moderate subgroup.
Agitation, apathy, and delusions are associated with volumes of a priori selected brain regions using clinical data and clinically acquired MRI scans. The ACC is an anatomic region common to these symptoms, particularly agitation and delusions, which closely mirror the findings of research-quality studies and suggest its importance as a behavioral hub.
Antidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability.
This study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up).
Participants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home.
Thirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND).
PATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy.
Depression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE.
PATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction: F[1,24.4] = 7.61, p = 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction: F[1,39.8] = 13.31, p = 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction: F[1,89] = 4.93, p = 0.0290) than ST-CI participants over the 24-week period.
PATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.
There is increasing evidence of an association between depressive symptoms and mild cognitive impairment (MCI) in cross-sectional studies, but the longitudinal association between depressive symptoms and risk of MCI onset is less clear. The authors investigated whether baseline symptom severity of depression was predictive of time to onset of symptoms of MCI.
These analyses included 300 participants from the BIOCARD study, a cohort of individuals who were cognitively normal at baseline (mean age = 57.4 years) and followed for up to 20 years (mean follow-up = 2.5 years). Depression symptom severity was measured using the Hamilton Depression Scale (HAM-D). The authors assessed the association between dichotomous and continuous HAM-D and time to onset of MCI within 7 years versus after 7 years from baseline (reflecting the mean time from baseline to onset of clinical symptoms in the cohort) using Cox regression models adjusted for gender, age, and education.
At baseline, subjects had a mean HAM-D score of 2.2 (SD = 2.8). Higher baseline HAM-D scores were associated with an increased risk of progression from normal cognition to clinical symptom onset ≤ 7 years from baseline (p = 0.043), but not with progression > 7 years from baseline (p = 0.194). These findings remained significant after adjustment for baseline cognition.
These results suggest that low levels of depressive symptoms may be predictive of clinical symptom onset within approximately 7 years among cognitively normal individuals and may be useful in identifying persons at risk for MCI due to Alzheimer’s disease.
Alzheimer's disease has become an important public health burden for older adults. Clinicians face a challenging task to efficiently evaluate cognition in dementia in clinical settings. We sought to assess the validity and inter-correlations of brief cognitive assessments in a cohort of severely demented patients.
In total, 49 individual patients (N = 49) ranging in age from 62 to 97 years old were included in this performance improvement project. Over the course of two–three sessions, five cognitive instruments were administered to each patient: Severe Impairment Battery (SIB), Severe Impairment Battery-8 (SIB-8), Mini Mental State Examination (MMSE), Severe Mini Mental State Examination (sMMSE) and Brief Interview of Mental Status (BIMS). We sought to assess patient factors that might have been barriers to optimal performance on cognitive/functional tests. Researchers assessed her impression of the participants’ difficulty comprehending instructions, distractibility, apparent fatigue, and frustration, which were the four barriers rated.
Data were analyzed for 49 patients from the inpatient dementia unit with a total of 51 samples. All of the inter-correlations between the five cognitive instruments had Spearman coefficients of (rs) > 0.7 and were statistically significant with p < 0.001. The SIB-8 and sMMSE were positively correlated with the SIB. The perceived barrier scores ranged from 0- no issue to 1-mild issue on all five cognitive instruments.
Brief cognitive tests designed for severe dementia such as the SIB-8 and sMMSE have been evaluated in this project to be shorter in administration duration and highly correlated with gold standard instruments: the SIB and MMSE.
There are relatively small but observable changes in functional ability in those without Mild cognitive impairment (MCI) or dementia. The present study seeks to understand whether these individuals go on to develop MCI or dementia by assessing the association between baseline Functional Activities Questionnaire (FAQ) and conversion independent and after adjustment for cognitive tests.
The NACC database was used to conduct the analysis of which 7,625 participants were initially identified as having more than one visit and who were cognitively normal at their first visit. Cox proportional hazards were used to fit three models that controlled for executive and non-executive cognitive domains. A similar model was used to assess the effect of FAQ subcategories on conversion.
Of these individuals, 1,328 converted to either MCI or dementia by visit 10. Converters had a total visit 1 FAQ score significantly higher than non-converters indicating more functional impairment at baseline. After adjustment for cognitive tests, the association between visit 1 FAQ and subsequent conversion was not attenuated. Doing taxes, remembering dates, and traveling were individually identified as significant predictors of conversion.
The FAQ can be used as an indirect measure of functional ability and is associated with conversion to MCI or dementia. There is a selective and significant association between changes in financial ability and conversion that is in accordance with other research of financial capacity.
Paul K. Kleinman, Department of Radiology, Boston Children’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA,
Andrew E. Rosenberg, Director of Anatomic Pathology and Director of Bone and Soft Tissue Pathology at the University of Miami Hospital and Professor of Pathology at the University of Miami Miller School of Medicine, Miami, Florida, USA,
Andy Tsai, Staff Pediatric Radiologist at Boston Children’s Hospital and Instructor in Radiology at Harvard Medical School, Boston, Massachusetts, USA
Fractures are common injuries in abused children, second only to cutaneous bruising (1). Although fundamental to the documentation of abuse, the fractures are rarely life-threatening and few result in long-term deformity. Specific types of fractures are known to be associated with abuse, and their recognition is important for their accurate identification and in understanding their significance.
Many reports of unexplained subdural hematomas (SDHs) in infants had appeared before Caffey’s historic 1946 article, but it was only after he associated these lesions with certain patterns of skeletal injury that the modern medical entity of child abuse was formulated (2). In a sense, recognition of the role of skeletal injuries in child abuse became the catalyst for the surge of interest in child maltreatment after Caffey’s original description.
In the years that followed, most reports of child abuse focused mainly on the radiologic alterations associated with the skeletal trauma (3–14). The confident documentation of skeletal injury, facilitated by characteristic radiologic alterations, provided investigators the opportunity to study the multiple facets of child abuse. Eventually, the blend of the clinical and the radiologic findings led Kempe, Silverman, and others to bring these associations to the status of the “battered child syndrome” (15).
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Needle thoracostomy is the prehospital treatment for tension pneumothorax. Sufficient catheter length is necessary for procedural success. The authors of this study determined minimum catheter length needed for procedural success on a percentile basis.
A meta-analysis of existing studies was conducted. A Medline search was performed using the search terms: needle decompression, needle thoracentesis, chest decompression, pneumothorax decompression, needle thoracostomy, and tension pneumothorax. Studies were included if they published a sample size, mean chest wall thickness, and a standard deviation or confidence interval. A PubMed search was performed in a similar fashion. Sample size, mean chest wall thickness, and standard deviation were found or calculated for each study. Data were combined to create a pooled dataset. Normal distribution of data was assumed. Procedural success was defined as catheter length being equal to or greater than the chest wall thickness.
The Medline and PubMed searches yielded 773 unique studies; all study abstracts were reviewed for possible inclusion. Eighteen papers were identified for full manuscript review. Thirteen studies met all inclusion criteria and were included in the analysis. Pooled sample statistics were: n=2,558; mean=4.19 cm; and SD=1.37 cm. Minimum catheter length needed for success at the 95th percentile for chest wall size was found to be 6.44 cm.
A catheter of at least 6.44 cm in length would be required to ensure that 95% of the patients in this pooled sample would have penetration of the pleural space at the site of needle decompression, and therefore, a successful procedure. These findings represent Level III evidence.
ClemencyBM, TanskiCT, RosenbergM, MayPR, ConsiglioJD, LindstromHA. Sufficient Catheter Length for Pneumothorax Needle Decompression: A Meta-Analysis. Prehosp Disaster Med. 2015;30(3):15
The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD.
We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013.
We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of “clinically significant A/A.” There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials.
This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.
Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses.
MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale – Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6–DS baseline)) – (placebo (DS week 6–DS baseline)).
In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06–1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09–1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment.
These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.
Many emergency physicians (EPs) order “confirmatory” abdominal computed tomography (CT) in young flank pain patients, despite a high clinical suspicion of renal colic and the risk of radiation exposure. We measured the adverse outcome rate among flank pain patients identified as not requiring abdominal CT by the EP on a data form, regardless of whether CT was eventually ordered. Our secondary objective was to describe diagnoses other than renal colic identified by CT in this population.
We conducted a prospective observational study at two community EDs. We asked staff EPs to complete a data sheet on patients ages 18 to 50 years with a first episode of flank pain, recording 1) if the flank pain was consistent with renal colic and 2) if the EP felt abdominal CT was indicated. Adverse outcomes (defined a priori as urgent surgical procedures, disability, or death) were assessed by research assistants at 4 weeks using telephone follow-up and a hospital records search.
We enrolled 389 patients; 353 completed follow-up (91%). The average age was 38.8 years, and 72.0% were male. Of 212 patients identified in the “CT not indicated” group, 2 had another diagnosis identified (unruptured diverticulitis and a ruptured ovarian cyst), but none had adverse outcomes (95% CI 0-1.4).
Adverse events were rare (< 1.5%) among patients < 50 years old with flank pain when CT was not required according to the clinical assessment of the EP. Future research should assess the adverse outcomes of withholding CT in low-risk patients using a larger patient sample.
Supernovae play an integral role in the feedback of processed material back into the interstellar medium (ISM) of galaxies and are responsible for most of the chemical enrichment of the universe. The rate of supernovae can also reveal the star formation histories. In a sample of 11 nearby galaxies observed with SINFONI, a strong linear correlation between [FeII]1.26 luminosity and Starburst 99-derived supernova rate is found on a pixel-pixel basis. In the very nearby archetypal starburst galaxy NGC 253, the excitation of molecular gas is a subject of debate. Using the correlation between [FeII] and supernova rate, we can determine if supernovae can account for the excitation of the bright observed near-infrared H2 emission.