Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.

Outcomes following hip fracture surgery: a 2-year prospective study.

OBJECTIVES: To describe the health outcomes in older people following hip fracture surgery. DESIGN, SETTING, AND PARTICIPANTS: A naturalistic prospective study of people who had undergone hip fracture surgery undertaken in three specialist inpatient orthopaedic units in Manchester, England, with follow-up for 2 years in primary care. One hundred forty-two people, age 60 and older who had undergone hip fracture surgery of whom 74 were interviewed at follow-up. MEASUREMENTS: Assessment of mood (using the Geriatric Depression Scale and Hospital Anxiety and Depression Scale), cognitive function (Mini-Mental State Examination), pain (Wong-Baker and McGill scales), tests of function (Up and Go Test, Gait Test and Functional Reach), and Sickness Impact Profile. RESULTS: Twenty-six percent of the original group had died by the time of the 2-year follow-up and associated with increasing age, poorer mobility, and higher levels of support. Sixteen percent of the group were found to be depressed, the only robust predictor of this being depression at entry to the study. There was a consistency in the presence or absence of depressive symptoms over the duration of the study. Forty-nine percent were able to walk independently at 2 years. CONCLUSION: The presence of depressive symptoms is associated with poor outcomes at 2 years. Few people recover from, or develop, depression over 2 years.

Val66Met in brain-derived neurotrophic factor affects stimulus-induced plasticity in the human pharyngeal motor cortex.

BACKGROUND & AIMS: Polymorphisms in brain-derived neurotrophic factor (BDNF) can affect brain and behavioral responses. However, little is known about the effects of a single nucleotide polymorphism (SNP) in BDNF, at codon 66 (the Val-Met substitution, detected in approximately 33% of the Caucasian population) on stimulation-induced plasticity in the cortico-bulbar system. We examined whether this SNP influenced outcomes of different forms of neurostimulation applied to the pharyngeal motor cortex. METHODS: Thirty-eight healthy volunteers were assessed for corticobulbar excitability after single-pulse, transcranial magnetic stimulation of induced pharyngeal electromyographic responses, recorded from a swallowed intraluminal catheter. Thereafter, volunteers were conditioned with pharyngeal electrical stimulation, or 2 forms of repetitive (1 and 5 Hz) transcranial magnetic stimulation (rTMS). Repeated measurements of pharyngeal motor-evoked potentials were assessed with transcranial magnetic stimulation for as long as 1 hour after the 3 forms of neurostimulation and correlated with SNPs at codon 66 of BDNF (encoding Val or Met). RESULTS: Pharyngeal electrical stimulation significantly increased the amplitude of motor-evoked potentials in individuals with the SNP that encoded Val66, compared to those that encoded Met66, with a strong GENOTYPE*TIME interaction (F8,112 = 2.4; P = .018). By contrast, there was a significant reduction in latencies of subjects with the SNP that encoded Met66 after 5-Hz rTMS (F3,60 = 4.9; P = .04). In addition, the expected inhibitory effect of 1-Hz rTMS on amplitude was not observed in subjects with the SNP that encoded Met66 in BDNF (F7,140 = 2.23; P = .035). CONCLUSIONS: An SNP in human BDNF at codon 66 affects plasticity of the pharyngeal cortex to different forms of neurostimulation. Genetic analysis might help select specific forms of neurostimulation as therapeutics for patients with disorders such as dysphagic stroke.

Outcomes of gastrocnemius-soleus complex lengthening for isolated equinus contracture in children with cerebral palsy.

BACKGROUND: The goal of the gastrocnemius-soleus complex (GSC) lengthenings in children with cerebral palsy (CP) is to achieve a plantigrade foot and normalize kinematics during gait. The study purpose was to evaluate the results of GSC lengthening for isolated equinus contracture in individuals with CP. It was hypothesized that GSC lengthenings would normalize passive ankle range of motion, kinematic, kinetic, and temporal spatial parameters. METHODS: Gait data from 15 able-bodied participants from the laboratory normal database and passive range of motion, kinematic, kinetic, and temporal spatial gait parameters, and oxygen cost were collected and analyzed for 27 individuals with CP (36 limbs) with isolated equinus contracture who received GSC lengthenings. Data were compared between preoperative and postoperative assessments. RESULTS: Mean age at baseline was 11.4 years (+/-3.2 y). Mean time between surgery and postoperative gait analysis was 1.3 years (+/-0.3 y). Passive range of motion measurements were obtained. Kinematic and kinetic data for the hip, knee and ankle, and temporal spatial parameters were obtained from a representative gait trial preoperatively and postoperatively. Paired t tests (P<0.05) determined whether preoperative data differed from postoperative data or from able-bodied data. The passive range of motion at the ankle was improved and normalized postoperatively. Ankle kinematics normalized without compensatory changes occurring at the knee or hip kinematics. Ankle moments and powers become more normal but did not completely normalize. Kinematics and kinetics of the hip and knee were not adversely affected. No changes in the temporal spatial data or oxygen cost occurred postoperatively. CONCLUSIONS: These data support the finding that with appropriate patient selection isolated GSC lengthening does not result in overcorrection. LEVEL OF EVIDENCE: Retrospective comparative study; level 3.

Treatment and prevention of depression after surgery for hip fracture in older people: randomized, controlled trials.

OBJECTIVES: To evaluate the effect of a psychiatric intervention in treating depression (treatment study) and the effect of a psychological treatment in preventing depression (prevention study) after hip fracture in older people. DESIGN: Two linked randomized, controlled trials. SETTING: Orthopedic units in Manchester, England. PARTICIPANTS: Two hundred ninety-three older people who had undergone surgery for a fractured hip: 121 in the treatment study and 172 in the prevention study. MEASUREMENTS: The Geriatric Depression Scale and Hospital Anxiety and Depression Scale for mood, functional tests for mobility and pain measures. RESULTS: There was a slight reduction in depressive symptoms in the active arm of the treatment study. In the prevention study, there was no significant difference in incident depression between the psychological intervention and treatment as usual. There were no differences in the functional and pain outcomes. CONCLUSION: The results from these two randomized, controlled trials show that, after hip fracture surgery, no statistically significant benefits can be achieved from a psychiatric intervention in people who are depressed or a psychological intervention to prevent the onset of depression.

White matter lesions account for all age-related declines in speed but not in intelligence.

MRI scans measured white matter lesion prevalence (WMLP) in 65 people ages 65-84 years who also took 17 cognitive tests: 3 tests of general fluid intelligence, 3 of vocabulary, 2 of episodic and 3 of working memory, 2 of processing speed, and 4 of frontal and executive function. Entry of age with WMLP into regression equations as predictors of test scores showed that inferences about the functional relationships between markers of brain aging and cognitive impairments are seriously misleading if they are based on simple correlations alone. A new finding that WMLP accounts for all of the age-related variance between individuals in tests of speed and executive ability but for none of the age-related variance in intelligence revises current hypotheses that gross brain changes affect general fluid intelligence and other mental abilities solely through their effects on information-processing speed.

Effects of global atrophy, white matter lesions, and cerebral blood flow on age-related changes in speed, memory, intelligence, vocabulary, and frontal function.

Brain images were obtained from 133 healthy people of ages 61-85 years who completed 20 tests of information processing speed, intelligence, frontal and executive function, memory, and vocabulary. Structural equation models examined relationships between cognitive test scores, ages and measurements of global age-associated atrophy, white matter lesions, and cerebral blood flow. These neurophysiological measures jointly account for all age-related variance in information processing speed. Speed entirely mediated relationships between neurophysiological measures and memory and partly mediated relationships between neurophysiological measures and intelligence and frontal function. Neurophysiological measures, but not calendar age, accounted for vocabulary scores. Cognitive slowing was responsible for some, but not all, age-related declines in mental function. Age-related declines in intelligence, frontal function, and speed were due to changes in different functional systems.

Losses in gross brain volume and cerebral blood flow account for age-related differences in speed but not in fluid intelligence.

Age-related gross head size; adjusted age-related change in brain volume and carotid and basilar blood flow; as well as scores on 3 tests of fluid intelligence (gf), 2 tests of information-processing speed, 2 memory tests, and 3 tests of executive function were obtained from 69 volunteers aged from 62 to 84 years. Brain volume negatively predicted scores on all 10 cognitive tasks, accounting for up to 78% of age-related variance in scores on the speed tasks and on 1 executive task. Cerebral blood flow (CBF) negatively predicted scores on 8 cognitive tasks, accounting for up to 36% of age-related variance in speed scores. However, neither brain volume nor CBF accounted for significant age-related variance between individuals on any of 3 gf tests. We conclude that speed, but not gf, is an exceptionally sensitive behavioral index of the progress of gross brain changes that affect cognition in old age and that speed and gf do not reflect integrity of the same functional systems.

Functional gene group analysis indicates no role for heterotrimeric G proteins in cognitive ability.

Previous functional gene group analyses implicated common single nucleotide polymorphisms (SNPs) in heterotrimeric G protein coding genes as being associated with differences in human intelligence. Here, we sought to replicate this finding using five independent cohorts of older adults including current IQ and childhood IQ, and using both gene- and SNP-based analytic strategies. No significant associations were found between variation in heterotrimeric G protein genes and intelligence in any cohort at either of the two time points. These results indicate that, whereas G protein systems are important in cognition, common genetic variation in these genes is unlikely to be a substantial influence on human intelligence differences.

Treatment and prevention of depression after surgery for hip fracture in older people: cost-effectiveness analysis.

OBJECTIVE: For older people who have had hip fracture surgery, to evaluate the cost-effectiveness of a nurse-led intervention in treating depression compared to treatment as usual (TAU), and to evaluate the cost-effectiveness of a psychological treatment for the prevention of depression. DESIGN: Two linked cost-effectiveness studies for the treatment and prevention of depression after hip surgery, from the perspective of health, social care, voluntary sector agencies and unpaid carers. SETTING: Orthopaedic units in Manchester, England. PARTICIPANTS: One hundred and twenty-one patients with Geriatric Depression Scale (GDS) scores greater than 6 were included in the treatment study and 172 patients with GDS scores less than or equal to 6 were enrolled in the prevention study. INTERVENTIONS: Nurse-led intervention for treating depression versus TAU; and cognitive behaviour therapy (CBT) for preventing depression following surgery for hip fracture. MAIN OUTCOME MEASURES: Outcomes were changes in HADS-depression scores at 6 weeks. Costs covered treatment and all service impacts. RESULTS: After 6 weeks, there were no significant differences in cost. However, the nurse-led intervention group had a lower mean HADS-depression score compared to TAU. In the prevention study, there were no significant differences in cost and depression score between patients treated with CBT and TAU. CONCLUSION: The results for this parallel randomized controlled study show that after hip fracture surgery a nurse-led intervention may be a cost-effective option for the treatment of depression in older people with depression. However CBT does not appear to be a cost-effective option for the prevention of depression in this population.

Emergency laparoscopic colectomy: does it measure up to open?

BACKGROUND: Laparoscopic colectomy has become the standard of care for elective resections; however, there are few data regarding laparoscopy in the emergency setting. METHODS: By using a database with prospectively collected data, we identified 94 patients who underwent an emergency colectomy between August 2005 and July 2008. Laparoscopic surgeries were performed in 42 patients and were compared with 25 patients who were suitable for laparoscopy but received open colectomy. RESULTS: The groups had similar demographics with no differences in age, sex, or surgical indications. Blood loss was lower (118 vs 205 mL; P < 0.01) and the postoperative stay was shorter (8 vs 11 d; P = 0.02) in the laparoscopic patients, and perioperative mortality rates were similar between the 2 groups (1 vs 3; P = 0.29). CONCLUSIONS: With increasing experience, laparoscopic colectomy is a feasible option in certain emergency situations and is associated with shorter hospital stay, less morbidity, and similar mortality to that of open surgery.

Predictors of incident depression after hip fracture surgery.

OBJECTIVE: Depression after hip fracture surgery is prevalent and associated with increased mortality rates and impaired functional recovery. The incidence of new-onset depressive symptoms in patients initially not depressed after hip fracture surgery and their relationship with functional recovery is unknown. METHODS: A cohort of 139 nondepressed elderly patients (>60 years) hospitalized for hip fracture surgery were followed up for six months. Clinically significant depressive symptoms were defined as a score of 7 or more on the 15-item Geriatric Depression Scale. RESULTS: The authors found a cumulative incidence rate of 20.5% adjusted for dropouts. Multiple Cox-regression analyses yielded the presence of subthreshold symptoms of depression, anxiety, pain, and cognitive impairment at baseline, the premorbid level of mobility, and a history of (treated) depression as risk factors for incident depression (p <0.05). A forward, conditional procedure identified postoperative pain (hazard ratio [HR] = 1.32, 95% confidence interval [CI]: 1.14-1.53, Wald chi(2) = 13.57, df = 1, p <0.001) and baseline anxiety (HR = 1.25, 95% CI: 1.08-1.44, Wald chi(2) = 8.86, df = 1, p = 0.003) as the strongest independent risk factors. Incident depression was associated with a less favorable outcome at 3 months follow-up. CONCLUSION: This exploratory study identified two treatable baseline characteristics that predicted incident depression in nondepressed patients after hip-fracture surgery.

Fear of falling more important than pain and depression for functional recovery after surgery for hip fracture in older people.

BACKGROUND: Depression and cognitive functioning have a negative impact on functional recovery after hip fracture surgery in older people, and the same has been suggested for pain and fear of falling. These variables, however, have never been studied together, nor has the timing of psychiatric assessment been taken into account. METHOD: Two parallel, randomized controlled trials were undertaken aiming to prevent and treat depression after hip fracture surgery in older people. Multiple logistic regression analyses corrected for age and pre-morbid level of functioning were performed to evaluate the effect of depressive symptoms (15-item Geriatric Depression Scale, GDS), pain (Wong-Baker pain scale), cognitive functioning (Mini-mental State Examination, MMSE) and fear of falling (Modified Falls Efficacy Scale, MFES) within 2 weeks after surgery and 6 weeks later on functional recovery at 6 months. Main outcome measures were performance-based measures (up-and-go test, gait test, functional reach) and the self-report Sickness Impact Profile (SIP) questionnaire to assess the impact of the hip fracture on activities of daily living (ADL). RESULTS: Two hundred and ninety-one patients participated and outcome measures for 187 (64%) patients were available at 6 months. All mental health variables interfered with functional recovery. However, in the final multivariate model, cognitive functioning and fear of falling assessed 6 weeks after surgery consistently predicted functional recovery, whereas pain and depressive symptoms were no longer significant. CONCLUSION: Fear of falling and cognitive functioning may be more important than pain and depression to predict functional recovery after hip fracture surgery. Rehabilitation strategies should take this into account.