The effects of medication adherence on study outcomes in randomized clinical trials: A role for cognitive dysfunction?

Medication nonadherence is common and has been associated with poor health outcomes. Older adults are especially likely to be non-adherent to their medications, as they often have more medications to manage and are at greater risk for cognitive dysfunction. Though less frequently examined, the association between cognitive dysfunction and nonadherence also likely extends to clinical trials research. The current study used archival data to examine the potential impact of cognitive dysfunction on adherence to a nutritional supplement as part of a 90-day randomized clinical trial in neurologically healthy middle-aged and older adults. Results showed overall cognitive performance was predictive of adherence to capsule intake when controlling for polypharmacy [F(1,157) = 6.53, p < .01]. These results suggest that cognitive dysfunction may impact findings from RCTs through its adverse impact on adherence to study protocol, possibly leading to greater treatment variance, artificially reduced treatment effects, lower study power, and distorted study outcomes and conclusions. A better understanding of methodological and statistical approaches to account for these unwanted effects are needed.

Performance of the Immediate Post-Concussion Assessment and Cognitive Testing Protocol Validity Indices.

OBJECTIVE: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a computerized neuropsychological test battery. Athletes provide preseason baseline ImPACT scores to which post-injury scores can be compared to aid concussion diagnosis. However, if baseline scores are not accurately representative of abilities, the utility of post-injury score comparison is diminished. For this reason, ImPACT includes low score thresholds on five validity indices to identify insufficient effort at baseline, though evidence of these indices' performance is limited. The present study examines the classification accuracy and concurrent validity of the existing ImPACT validity indices and three proposed indices (Word Memory Correct Distractors, Design Memory Correct Distractors, Total Symptom Score). METHODS: The ImPACT, Word Memory Test (WMT) and Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) were administered to 242 undergraduate students. Participants were instructed to either give full effort on testing or to simulate SRC. RESULTS: Sensitivity of the existing ImPACT validity indices was marginally improved with adjusted score thresholds while maintaining acceptable specificity (0.90). Alternative score thresholds and novel validity indices demonstrated adequate specificity while improving sensitivity overall. Positive and negative predictive powers are provided to inform use of protocol validity indices across diverse treatment settings. CONCLUSIONS: The existing ImPACT indices' high specificity at the expense of lower sensitivity compared to external validity measures may under-identify poor effort, resulting in premature return-to-play decisions for athletes with concussion. Improvements or additions to the existing indices may raise sensitivity while maintaining acceptable specificity, aiding in the protection of athletes and safe athletic participation.

Obesity is associated with memory deficits in young and middle-aged adults.

Recent findings suggest obesity is associated with reduced memory performance in older adults. The present study examined whether similar deficits also exist in younger adults and the degree to which the relationship between body mass index (BMI) and memory varies as a function of age. Prior to inclusion, participants were rigorously screened and excluded for medical conditions known to impact cognitive functioning, including neurological disorders, head injury, cardiovascular disease, and diabetes. A total of 486 healthy adults completed a verbal list-learning task. Participants were categorized into normal weight, overweight, and obese groups based on their BMI. Performance on learning, delayed recall, and recognition performance were compared across BMI groups. Results showed obese individuals had poorer memory performance when comparing persons across the adult lifespan (age 21-82 yr), but also when examining only younger and middle-aged adults (age 21-50 yr). Regression analyses found no evidence of an interaction between BMI and age on any memory variable, suggesting the relationship between BMI and memory does not vary with age. These findings provide further support for an independent relationship between obesity and reduced memory performance and suggest these effects are not limited to older adults. Further research is needed to identify etiological factors.

Executive functions predict weight loss in a medically supervised weight loss programme.

BACKGROUND: Deficits in executive functions are related to poorer weight loss after bariatric surgery; however, less is known about the role that these deficits may play during participation in nonsurgical weight loss programmes. This study examined associations between objectively measured executive functions and weight loss during participation in a medically supervised weight loss programme. METHODS: Twenty-three adult patients (age 50.4 ± 15.1, BMI 44.2 ± 8.8, 68% female, 92% White) enrolled in a medically supervised weight loss programme, involving prescription of a very low calorie diet and strategies to change eating and activity behaviours, underwent comprehensive computerized testing of executive functions at baseline. Weight was obtained at baseline and 8 weeks. Demographic and clinical information were obtained through medical chart review. RESULTS: Participants lost an average of 9.8 ± 3.4% of their initial body weight at 8 weeks. Fewer correct responses on a set-shifting task and faster reaction time on a response inhibition task were associated with lower weight loss percentage at 8 weeks after adjusting for age, education and depressive symptoms. There were no associations between performance on tests of working memory or planning and weight loss. CONCLUSIONS: This study shows that worse performance on a set-shifting task (indicative of poorer cognitive flexibility) and faster reaction times on a response inhibition test (indicative of higher impulsivity) are associated with lower weight loss among participants in a medically supervised weight loss programme. Pre-treatment assessment of executive functions may be useful in identifying individuals who may be at risk for suboptimal treatment outcomes. Future research is needed to replicate these findings in larger samples and identify underlying mechanisms.

Cognitive dysfunction predicts poorer emotion recognition in bariatric surgery candidates.

OBJECTIVE: Deficits in traditional cognitive domains (e.g. executive function and memory) are common in persons with severe obesity, but it is unclear if this pattern of dysfunction extends to social cognition. The present study examined whether cognitive impairment was associated with poorer emotion recognition in bariatric surgery candidates. METHODS: One hundred sixteen bariatric surgery candidates (mean age = 43.62 ± 11.03; 81% female) completed the computerized Integneuro test battery as part of a larger study visit. In addition to assessing traditional cognitive domains, the Integneuro also includes an emotion recognition measure. This task presents 48 faces (eight different individuals depicting neutral, happiness, fear, sadness, anger and disgust), and participants must choose the correct verbal label from six expression options. Number of correct responses and average reaction time for correct responses served as primary dependent variables. RESULTS: Stepwise multiple regression analyses revealed that older age, more maze errors, and history of hypertension predicted less accuracy in emotion recognition (adjusted R2 = .22, F[3, 111] = 11.86, p < .001) and that slower switching of attention-digits, worse long-delay recall, and older age predicted speed of responses (adjusted R2 = .26, F[3, 111] = 13.00, p < .001). DISCUSSION: Results show that cognitive dysfunction is associated with poorer performance on a computerized test of emotion recognition, consistent with those in persons with a range of psychiatric and neurological disorders. Additional work is needed to clarify the mechanisms and functional impact of these impairments, especially in relation to weight loss following bariatric surgery.

The effects of coaching on the sensitivity and specificity of malingering measures.

This study sought to identify patterns of performance indicative of malingering on the Auditory Verbal Learning Test (AVLT). Participants were randomly assigned to perform normally, simulate head injury, or simulate head injury with warning that there might be attempts to detect malingering. Participants completed an expanded AVLT and a forced-choice task, in addition to several other memory tests. The warned simulators performed worse than normals on the forced-choice task, but better than those simulating head injury without a warning, suggesting that the warned subjects recognized forced choice as a malingering test. A combination of AVLT indices was able to predict group status for both nai;ve and warned malingerers (73.6% for nai;ve malingerers, 84.8% for warned, no false positives). The forced-choice measure detected only 31.6% of the nai;ve malingerers when specificity was maximized, and detected only 6.5% of the warned malingerers, a significant drop in detection rate. Findings suggest that pattern of performance indices are useful in detecting malingering, even when subjects are aware of attempts to detect malingering.

Uncontrolled eating is associated with reduced executive functioning.

Accumulating evidence indicates obesity is associated with reduced cognitive functioning, particularly attention and executive function, as well as maladaptive eating behaviour such as uncontrolled eating. The current study examined relationships between eating patterns and attention/executive function test performance in lean and obese individuals. Sixty-two (32 lean, 30 obese) healthy young adults (21.13 ± 2.31 years; 56.5% female) completed the abbreviated Three-Factor Eating Questionnaire (TFEQ-R18) to assess eating patterns, including uncontrolled eating, cognitive restraint, and emotional eating. The Go/No-Go (GNG), Running Memory Continuous Performance Test (RCMPT) and Standard Continuous Performance Test from the Automated Neuropsychological Assessment Metrics-4 were administered as measures of executive functioning and attention. An independent samples t-test revealed greater report of uncontrolled eating in obese compared with lean participants (t[60] = -2.174, P < 0.05; d = -0.55) but no differences in cognitive restraint or emotional eating. Multivariate analysis of variance revealed cognitive differences between lean and obese groups (F[6, 54] = 3.86, P < 0.005; λ = 0.70; ηp(2) = 0.30), which were driven by GNG reaction time (F[1, 59] = 8.36, P < 0.01, d = 0.74). Pearson bivariate correlations revealed a positive correlation between uncontrolled eating and reaction time on GNG (r = 0.343, P < 0.05) and RMCPT (r = 0.267, P < 0.05) in all participants. Relative to lean participants, obese individuals reported higher levels of uncontrolled eating and exhibited slower performance on a task of inhibitory control. In the full sample, greater self-reported dyscontrol in eating behaviour was related to slower inhibitory control and working memory. Results support a link between executive function and control of eating behaviour. Obese individuals may be more vulnerable to difficulties in these domains relative to those who are lean.

Serum insulin like growth factor-1 is associated with working memory, executive function and selective attention in a sample of healthy, fit older adults.

The present study examined the association between serum insulin like growth factor-1 (IGF-1) concentrations and cognitive function in a sample of healthy, fit older adults (age: 70.8±9.3 years, body mass index (BMI): 27.3±5.7). Participants reported to the laboratory and basic anthropometric data were collected, followed by a fasted blood draw to quantify serum IGF-1. Participants then underwent cognitive testing that included the Mini-Mental Status Exam (MMSE), Trail Making Test A and B, Ruff's 2 and 7 test of selective attention and Letter Number Sequencing. Results showed the participants were generally cognitively intact (MMSE 27.6±1.8). Significant partial correlations (controlled for age, gender and years of education) emerged between serum IGF-1 concentrations and the total (r=0.381, P=0.030) and longest trial (r=0.455, P=0.011) on Letter Number Sequencing. Similar partial correlations yielded significant relationships between serum IGF-1 and Ruff's Automatic Detection Errors (r=-0.495, P=0.006), Controlled Speed Errors (r=-0.598, P=0.002) and errors made on the Trial Making Test part B (r=-0.466, P=0.010). These findings suggest that fasting levels of serum IGF-1 are related to higher levels of cognitive performance in healthy older adults, including working memory, selective attention and executive function. Further work is needed to more clearly determine possible mechanisms.

Serum brain-derived neurotrophic factor is associated with reduced appetite in healthy older adults.

OBJECTIVE: Loss of appetite and body mass are common in older adults and are associated with negative consequences. Research indicates that these processes likely involve increases in serum brain-derived neurotrophic factor (BDNF). Animal and human models demonstrate that BDNF may serve a regulatory function in food intake, but no study has addressed the possibility that BDNF may be involved in appetite reduction and loss of body mass in older adults. DESIGN AND PARTICIPANTS: 34 older adults without significant neurological or psychiatric history underwent fasting blood draw and measurement of body composition. Appetite and eating behavior were assessed by questionnaire and related to serum BDNF levels. RESULTS: Partial correlations showed serum BDNF levels were inversely related to appetite (r = -.38, p = .02). No significant correlations emerged between serum BDNF and age, diet, or body composition. CONCLUSIONS: The current study extends past work and shows that BDNF is associated with appetite in healthy older adults. Further work is needed to clarify mechanisms for these findings, particularly prospective studies.

"Expectation as etiology" versus "the good old days": postconcussion syndrome symptom reporting in athletes, headache sufferers, and depressed individuals.

The present study explored the explanatory power of Mittenberg's "expectation as etiology" theory for the persistence of postconcussion syndrome (PCS) complaints. One hundred forty-one participants completed a PCS symptom checklist under 2 conditions. Normal controls, healthy athletes and depressed individuals reported current symptoms and symptoms expected following a hypothetical mild head injury. Head-injured athletes, chronic headache sufferers, and a 2nd sample of normal controls reported current symptoms and retrospective symptoms (prior to their injury/illness or from some point in the past). Depressed individuals reported more current symptoms than normal controls and healthy athletes, demonstrating that "PCS" symptoms are not specific to PCS. All groups expected more symptoms following mild head injury than currently experienced, supporting the idea that individuals expect negative consequences following head injury. However, healthy athletes expected fewer symptoms than normals or depressed individuals, possibly due to preexisting expectations for speedy recovery. Both head-injured athletes and headache sufferers reported more current symptoms than the past, but not at a rate lower than baseline of normal controls. Results suggest that the "expectation as etiology" hypothesis may be too specific, and that, following any negative event, people may attribute all symptoms to that negative event (the "good old days" hypothesis).

Efficacy of the full and abbreviated forms of the Portland Digit Recognition Test: vulnerability to coaching.

The present study compared the efficacy of the abbreviated and the full scale PDRT in simulated malingerers and effortful controls. A total of 80 undergraduates were randomly assigned to normal effort, naïve simulators, informed simulators, and simulators with information and warning about malingering detection groups. Comparison shows abbreviated forms are superior to the full scale PDRT at detecting malingerers. The conservative abbreviated form detected 80% of the Naïve and Informed malingerers and 35% of the Warned. Warned Simulators were overall better at avoiding detection than Naïve or Informed Simulators.

Exaggeration index for an expanded version of the auditory verbal learning test: robustness to coaching.

Recent research suggests that effort detection measures based on patterns of neuropsychological performance may be more robust to coaching than traditional effort detection measures. In the present study, we evaluated the Exaggeration Index for an extended version of the Auditory Verbal Learning Test (EI-AVLTX), a recently developed effort detection instrument based on patterns of performance on the AVLT using a simulated malingering paradigm. In two independent samples, the EI-AVLTX was1 found to be relatively sensitive and specific to malingering, and robust to the effects of a warning about malingering detection.