Change In Cognitive Test Performance Research Articles

Abstract B116: Cognitive performance and cognitive decline following cancer among middle-aged and older adults in the study of Latinos-investigation of neurocognitive aging and HCHS/SOL

Abstract BACKGROUND: Cognitive impairment is a frequently reported side-effect of cancer therapies affecting attention, concentration, memory, and executive function. However, the long-term impacts of cancer and its treatments on cognitive function and cognitive decline in Hispanics/Latinos is unknown. Herein, we examined the associations between a self-reported history of cancer and cognitive test performance cross-sectionally and longitudinally among middle-aged and older Hispanic/Latino adults. METHODS: Participants included 9,639 Hispanic/Latino adults [mean age=56.4 (SE=0.14); 54.7% female] of diverse backgrounds [30.8% Mexican, 27.2% Cuban, and 18.1% Puerto Rican; 10.0% Central American; 9.0% Dominican; and 7% South American] from the population-based, prospective, multi-site Hispanic Community Health Study/Study of Latinos. At enrollment in 2008-2011 (Visit 1), participants self-reported their history of cancer (yes/no) and cancer site(s). Cognitive function was assessed at Visit 1 and again at a 7-year follow-up assessment (Visit 2) using the Brief-Spanish English Verbal Learning Test (BSEVLT-Sum, episodic learning; and BSEVLT-Recall, memory), the Word Fluency Test (WF, verbal fluency), and the Digit Symbol Substitution Test (DSS, processing speed and executive functioning) via the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). Changes in cognitive test performance were calculated using survey linear regression models predicting cognitive performance at Visit 2 as a function of Visit 1 cognitive performance with adjustment for time between assessments. Test scores/changes in tests scores were standardized and averaged as composites of global cognition/cognitive change. We used survey linear regression models to estimate the adjusted associations between history of cancer and baseline and longitudinal cognitive test performance. We examined these associations overall and by sex and for the most prevalent sex-specific cancers [i.e., cervical (n=121), breast (n=115), uterine (n=67), and prostate (n=48) cancers]. RESULTS: Cross-sectionally, a history of cancer (n=546) versus no history of cancer (n=9,093) was associated with higher WF scores (β=0.13, SE=0.06; P=0.03) and global cognition (β=0.08, SE=0.04; P=0.06) among all participants overall. Among men, but not among women, a history of cancer was associated with longitudinal increases in SEVLT-Sum (β=0.29, SE=0.14; P=0.04; PInteraction=0.04), and SEVLT-Recall (β=0.36, SE=0.15; P=0.02; PInteraction=0.01) scores. Among women, a history of cervical cancer was associated with longitudinal decreases in SEVLT-Recall scores (β=-0.30, SE=0.13; P=0.03) and among men, a history of prostate cancer was associated with higher baseline WF scores (β=0.29, SE=0.12; P=0.02). CONCLUSION: Cancer or its treatments may influence long-term cognition among Hispanics/Latino cancer survivors. The potential impacts of cancer or cancer treatment on cognition may vary by sex or cancer type. Citation Format: Humberto Parada Jr., Margaret Pichardo, Linda C. Gallo, Frank J. Penedo, David J. Lee, Gregory A. Talavera, Hector M. Gonzalez. Cognitive performance and cognitive decline following cancer among middle-aged and older adults in the study of Latinos-investigation of neurocognitive aging and HCHS/SOL [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B116.

Effects of Stressful Events and Perceived Stress on Cognitive Change Among Depressed Older Adults

<h3>Introduction</h3> Stress is thought to exacerbate cognitive decline in older adults, especially those with late life depression (LLD); however, the specific aspects of stress that are especially deleterious and the aspects of cognition they affect are not clear. For example, it is not known whether the effects result from the exposure to stressful life events or whether it is the perception of stress that is salient, and whether these relate to the domains of cognition affected. We hypothesized that the number of stressful events and the magnitude of perceived stress in older adults with LLD at baseline would be associated with cognitive decline over 2 years. <h3>Methods</h3> lder adults (ages 60-90 years) with LLD (n=124, mean age 71.5 years) and never-depressed elderly healthy controls (HCs) (n=39, mean age 74.6 years) were assessed at three time points each one year apart for number of stressful life events within the prior year using the Duke Depression Evaluation Scale, and perceived stress within the prior six months, and with five neurocognitive tests that included the Trail Making (Trail Making B – Trail Making A), Benton Visual Retention Test, Symbol Digit Modalities Test (Processing Speed), Logical Memory Delayed Recall II and Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Associations were examined (Spearman correlations) between baseline measures of the number of stressful life events and the perception of stress with change in cognitive test performance over time from baseline to year 1 and to year 2. Associations between stress measures and changes in the cognitive measures were considered significant at p<0.05. <h3>Results</h3> Only the LLD group showed a significant association between stress and cognitive changes. The level of perceived stress at baseline was associated with a decline on Trail Making from baseline to 1 year (r=0.22, pcorr=0.022); this association was stronger when assessed from baseline to 2 years (r=0.29, p=0.0058). <h3>Conclusions</h3> This study suggests that for older adults with LLD it was the perception of stress at baseline, not the number of stressful life events at baseline, that was associated with decline in executive functioning in the following 2 years. The findings highlight the importance of assessing the perception of stress in LLD, as individuals with LLD and high levels of perceived stress may be at risk for decline in executive functioning. Further study is warranted on adverse effects of perceived stress in LLD and the potential for preventing decline in executive functioning by reducing levels of perceived stress. <h3>Funding</h3> National Institute of Mental Health Grant R01 MH108578; The Leo and Anne Albert Charitable Trust

Change in self-reported cognitive symptoms after mild traumatic brain injury is associated with changes in emotional and somatic symptoms and not changes in cognitive performance.

To investigate (a) whether self-reported cognitive symptoms after mild traumatic brain injury (MTBI) are associated with cognitive test performances, and (b) whether improvement in self-reported symptoms from 2 weeks to 3 months after MTBI is associated with improvement in cognitive test performances. Patients with MTBI (n = 135), aged 16-59, who initially presented to the emergency department, completed the Rivermead Post Concussion Symptoms Questionnaire (RPQ), the Brief Symptom Inventory 18, and cognitive tests (i.e., Controlled Oral Word Association, Coding, Rey Auditory Verbal Learning, and Trail Making test) at 2 weeks and 3 months after MTBI. Using Spearman's rank correlations (ρ), associations were examined between self-report measures and cognitive test performances at each time point and between change scores (i.e., 3-month score minus 2-week score) on each outcome. At 3 months, 27% reported cognitive symptoms to some extent. At both assessments, greater severity of RPQ cognitive symptoms was very weakly associated with worse cognitive test performances (2-week ρ range = -0.19 to -0.01; 3-month ρ range = -0.20 to -0.10). RPQ cognitive symptoms were, however, strongly related to greater somatic and emotional symptoms. Change in self-reported cognitive symptoms from 2 weeks to 3 months was not associated with change in cognitive test performance. In contrast, change in self-reported cognitive symptoms was strongly associated with change in emotional (ρ = 0.58) and somatic symptoms (ρ = 0.57). These findings indicate that improvements in subjective cognitive symptoms after MTBI co-occur with improvements on other subjective metrics, but are not related to improvements in objectively measured cognitive functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy

Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited. We examined long-term cognitive effects of CBD in adults with TRE as part of an ongoing prospective, open-label safety study. Twenty-sevenadults with TRE (mean age: 34[SD +14], female 52%) enrolled in the UAB CBD program completed standardized cognitive testing (NIH Toolbox Cognition Battery (NIHTB-CB)) at pre-CBD administration baseline and at one-yearfollow-up. Participants were receiving stable CBD dose at the time of one-year testing (mean=36.5mg/kg/day). The NIHTB-CB consisted of two global composite scales (Fluid and Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language. All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit. Statistical analyses consisted of t-test, Pearson correlation coefficient, and linear regression. At baseline, cognitive test performance was below average for both global composite scales (Fluid: 71 [±18] range: 46–117) and Crystallized (76 [±15] range: 59–112)]. Longitudinal analysis revealed no significant group change across the two global composite scales. Of the seven individual cognitive tests, none changed significantly over time. No correlation was found between the cognitive change scores and CBD dose (all P's≥0.21). Change in cognitive test performance was not associated change in seizure severity rating. These findings are encouraging and indicate that long-term administration of pharmaceutical grade CBD is overall cognitively well-tolerated in adults with TRE.

Exercise Test Performance Reveals Evidence of the Cardiorespiratory Fitness Hypothesis.

Positive physiologic and cognitive responses to aerobic exercise have resulted in a proposed cardiorespiratory (CR) fitness hypothesis in which fitness gains drive changes leading to cognitive benefit. The purpose of this study was to directly assess the CR fitness hypothesis. Using data from an aerobic exercise trial, we examined individuals who completed cardiopulmonary and cognitive testing at baseline and 26 weeks. Change in cognitive test performance was not related to CR fitness change (r2 = .06, p = .06). However, in the subset of individuals who gave excellent effort during exercise testing, change in cognitive test performance was related to CR fitness change (r2 = .33, p < .01). This was largely due to change in the cognitive domain of attention (r2 = .36, p < .01). The magnitude of change was not explained by duration of exercise. Our findings support further investigation of the CR fitness hypothesis and mechanisms by which physiologic adaptation may drive cognitive change.

A Meta-analytic Review of Non-specific Effects in Randomized Controlled Trials of Cognitive Remediation for Schizophrenia.

Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, improvements in cognitive performance are often observed in the control groups of RCTs as well. There has been no comprehensive examination of change in control groups for CR, which may inform trial methodology and improve our understanding of measured outcomes for cognitive remediation. In this meta-analysis, we calculated pre-post change in cognitive test performance within control groups of RCTs in 32 CR trials (n = 794 participants) published between 1970 and 2011, and examined the association between pre-post change and sample size, duration of treatment, type of control group, and participants' age, intelligence, duration of illness, and psychiatric symptoms. Results showed that control groups in CR trials showed small effect size changes (Cohen's d = 0.12 ± 0.16) in cognitive test performance over the trial duration. Study characteristics associated with pre-post change included participant age and sample size. These findings suggest attention to change in control groups may help improve detection of cognitive remediation effects for schizophrenia.

Impact of Differential Attrition on the Association of Education With Cognitive Change Over 20 Years of Follow-up: The ARIC Neurocognitive Study

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.

Cognitive Outcomes After Sertaline Treatment in Patients With Depression of Alzheimer Disease

Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo. Placebo-controlled, randomized, double-blind trial. Outpatient memory clinics at five academic medical centers in the United States. A total of 131 patients with dAD (60 men) and Mini-Mental State Examination scores of 10-26. Sertraline (n = 67), target dose of 100 mg daily or matching placebo (n = 64). Caregivers received standardized psychosocial intervention throughout the trial. Mini-Mental State Examination, cognitive subscale of the Alzheimer's Disease Assessment Scale, letter fluency, backward digit span, Symbol Digit Modalities Test, and Finger Tapping Test, administered at baseline, and 8, 16, and 24 weeks following baseline. A series of linear models indicated no effect of treatment or of depression remission on cognitive test performance at 24 weeks. Regardless of treatment condition, very little change in cognitive test performance was noted in general. Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo.

Estimating the Temporal Evolution of Alzheimer's Disease Pathology with Autopsy Data

The temporal growth of Alzheimer's disease (AD) neuropathology cannot be easily determined because autopsy data are available only after death. We combined autopsy data from 471 participants in the Honolulu-Asia Aging Study (HAAS) into latent factor measures of neurofibrillary tangle and neuritic plaque counts. These were associated with intercept and slope parameters from a latent growth curve (LGC) model of 9-year change in cognitive test performance in 3244 autopsied and non-autopsied HAAS participants. Change in cognition fully mediated the association between baseline cognitive performance and AD lesions counts. The mediation effect of cognitive change on both AD lesion models effectively dates them within the period of cognitive surveillance. Additional analyses could lead to an improved understanding of lesion propagation in AD.

Effects of sertindole on cognition in clozapine‐treated schizophrenia patients

To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial. A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Participants displayed substantial cognitive deficits, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative Syndrome (PANSS) subscales, Global Assessment of Functioning subscale (GAF-F) and Clinical Global Impression (CGI) with 20 neurocognitive indices was conducted, but no significant correlations were found. Second, we tested change from baseline to endpoint for the PANSS, GAF-F, and CGI, vs. the concomitant changes in cognitive test performance, and found no significant correlations. The clozapine-treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect on cognition of augmenting clozapine treatment with another antipsychotic drug.

Selective cerebral perfusion for thoracic aortic surgery: Association with neurocognitive outcome

Optimal brain protection for aortic arch surgery remains unclear. This prospective study examined neurocognitive outcomes in cardiac and thoracic aortic surgical patients, including a small cohort who underwent selective cerebral perfusion. Fifty-seven adult cardiac and thoracic aortic surgical patients underwent preoperative and postoperative neurocognitive testing. Patients were divided into 3 groups. Group 1 patients underwent procedures with cardiopulmonary bypass alone (n = 24), group 2 patients with cardiopulmonary bypass and hypothermic circulatory arrest (n = 23), and group 3 patients with cardiopulmonary bypass, hypothermic circulatory arrest, and anterograde selective cerebral perfusion (n = 10). Changes in 14 neurocognitive test scores and 6 neurocognitive domain scores (Attention, Speed, Language, Memory, Executive Function, and Motor Function) were evaluated. Multiple regression analyses examining the relationships of cardiopulmonary bypass time, hypothermic circulatory arrest time, and selective cerebral perfusion time with change in cognitive test performance revealed that selective cerebral perfusion time (range, 39-83 minutes) was a significant predictor of decline in performance on memory and language tests. Hypothermic circulatory arrest (range, 14-40 minutes) and cardiopulmonary bypass (range, 70-369 minutes) times were unrelated to decline. Complex thoracic aortic repairs requiring prolonged selective cerebral perfusion were associated with decline in neurocognitive function. It is unclear whether the complexity of the repair necessitating prolonged selective cerebral perfusion or the perfusion technique itself contributed to neurocognitive decline. Prospective multicenter neurocognitive evaluations are necessary to assess the relative merits of current brain protection strategies in thoracic aortic surgery.

Activity engagement is related to level, but not change in cognitive ability across adulthood.

It is unclear whether the longitudinal relation between activity participation and cognitive ability is due to preserved differentiation (active individuals have higher initial levels of cognitive ability), or differential preservation (active individuals show less negative change across time). This distinction has never been evaluated after dividing time-varying activity into its two sources of variation: between-person and within-person variability. Further, few studies have investigated how the association between activity participation and cognitive ability may differ from early to older adulthood. Using the PATH Through Life Project, we evaluated whether between- and within-person variation in activity participation was associated with cognitive ability and change within cohorts aged 20-24 years, 40-44 years, and 60-64 years at baseline (n = 7,152) assessed on three occasions over an 8-year interval. Multilevel models indicated that between-person differences in activity significantly predicted baseline cognitive ability for all age cohorts and for each assessed cognitive domain (perceptual speed, short-term memory, working memory, episodic memory, and vocabulary), even after accounting for sex, education, occupational status, and physical and mental health. In each case, greater average participation was associated with higher baseline cognitive ability. However, the size of the relationship involving average activity participation and baseline cognitive ability did not differ across adulthood. Between-person activity and within-person variation in activity level were both not significantly associated with change in cognitive test performance. Results suggest that activity participation is indeed related to cognitive ability across adulthood, but only in relation to the starting value of cognitive ability, and not change over time.

The importance of cross-national and cross-cultural research in understanding the central nervous system complications of HIV disease

Ninety percent of all HIV disease exists outside of the northern hemisphere, and in countries without the same public health and healthcare systems that we enjoy. We can forget that our citizens with access to medical care enjoy the potential for near normal life expectancy, whereas those in sub-Saharan Africa, for example, may consider themselves privileged to receive any ART. Thus, we are faced with two epidemics. One of them is being aggressively controlled with medication, although prevention of the initial infection remains a major weakness. The second epidemic not only has rampant infection, but has limited resources for diagnosis and limited treatment options. Research tools, especially those that are useful for tracking the clinical manifestations of HIV must be able to be used in both of the epidemics. The problem is exacerbated by the fact that among the medically resource limited areas of the world, differences in language, culture and education relative to resource-rich areas could make comparisons difficult, if not impossible. The most exciting aspect of the data reported by Cysique et al. (pp. 983–990) is that by using tests that were originally developed in the West, primarily in the context of localization of central nervous system (CNS) dysfunction following stroke, tumor, or similar conditions, the team from China and the University of California San Diego (UCSD) HIV Neurobehavioral Research Center were able to obtain valid and reliable data. With careful analysis and interpretation of the data, neuropsychological tests in the United States can be used to evaluate HIV-associated cognitive impairment in an international setting such as China. Unfortunately, the data revealed that HIV disease, as we knew it in the West 10 years ago, is still alive and well elsewhere. The good news is that once treatment is initiated, the signs/symptoms of CNS dysfunction are in many cases brought under control. The strength of the study is the use of longitudinal HIV-seronegative normative data collected locally in China as a comparison group. From a public health policy perspective, the data also demonstrate the critical importance of early and effective control of viral replication and reconstitution of the immune system. Decline in neuropsychological test performance was linked to lower nadir CD4+ cell counts, having AIDS at study entry, and having poorer treatment response (i.e., detectable HIV RNA while on HAART). If immune status did not improve during the observation period, this was also associated with declining test performance. Confounding conditions associated with cognitive impairment also need to be considered when evaluating the data. In particular, a previous study by the same group found that hepatitis C coinfection was also associated with an increased risk of cognitive impairment among HIV-infected individuals in China. However, data from the current study suggest that hepatitis C coinfection was not related to subsequent cognitive decline. In evaluating HIV-associated cognitive impairment in an international setting, one needs to consider the impact of HIV subtype. In the United States, HIV subtype B is predominant whereas in China, B, C, and B/C recombinants are the predominant subtypes. Other studies suggest that subtype C may be associated with less cognitive impairment due to a mutation in the HIV subtype C tat gene [1]. The impact of HIV subtype on both baseline cognitive performance and cognitive decline is an area that requires further study in China. The change in cognitive test performance was also linked to other aspects of behavior. Those individuals whose performance declined were more likely to have a clinical depression at follow-up (21 versus 9%), and to have declining independence in activities of daily living. Whereas cognition, mood, and functional independence are tightly interrelated, these data demonstrate that the changes observed by the study team were not simply a statistical phenomenon, but had a clear impact on the ability of the patients to function effectively in their social and work environments. To the extent that the rural community in China is more intergenerational than other Western areas, the impact of such alterations could be felt across three or more generations, those of the patient, their children, and their parents (and perhaps, grandparents or grandchildren). In cultures that rely on cross-generational support for the effective functioning of the community, loss (or decreased abilities) of one link in the chain can have widespread impact.

A Longitudinal Investigation of Perceived Control and Cognitive Performance in Young, Midlife and Older Adults

ABSTRACT Longitudinal associations between generalized control beliefs (one's perceived capacity to influence events) and cognitive test performance were examined in a population-based sample of young, midlife and older adults. Participants provided measures of perceived control, self-assessed health, education and depression and anxiety symptoms, and completed cognitive tests at two assessments, 4 years apart. For each age group, baseline (between-person) control was positively related to performance on tests of memory (immediate recall and digits backwards), speed (Symbol Digit Modalities Test and choice reaction time) and verbal intelligence (Spot-the-Word). Interaction effects indicated stronger associations of between-person control beliefs with indices of speed for the older age group relative to the younger groups. Within-person changes in control were not significantly associated with changes in cognitive test performance over the study interval. Implications of the findings for self-efficacy based interventions designed to promote cognitive functioning are discussed.

Assessing cognitive change in Parkinson's disease: Development of practice effect-corrected reliable change indices

Serial assessments of cognitive functioning in individuals with Parkinson's disease (PD) are commonly used for the detection of incident dementia and neurobehavioral changes associated with treatments using neuromodulation (e.g., deep brain stimulation) and pharmacological agents (e.g., cholinesterase inhibitors). This study provides test–retest stability, expected practice effects, and practice-corrected reliable change indices for several commonly used neuropsychological tests from 62 older adults with mostly mild PD who underwent repeat evaluations approximately 17 months apart. At the group level, results showed adequate test–retest reliability (Spearman's rho range = 0.24–0.86) and generally small practice effects (Cohen's d range = 0.00–0.50). Application of reliable change indices using 90% confidence intervals showed the expected number of individuals (generally 10% or fewer) with statistically meaningful improvements (range = 0–12%) or declines (range = 2–8%) in cognitive performance at retest. Limitations discussed include ceiling effects at test baseline, sample homogeneity, interpretative cautions, and generalizability of study results. These data may be useful to researchers and clinicians interested in determining the statistical significance of changes in cognitive test performance in persons with PD over a 1- to 2-year interval.

Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial

Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested. Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined. No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance. This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases.

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans.Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE ∈4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE ∈4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p<0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.

The Progression of Cognition, Psychiatric Symptoms, and Functional Abilities in Dementia With Lewy Bodies and Alzheimer Disease

Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n = 55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment.

Cognitive Function Remains Unchanged After Endarterectomy of Unilateral Internal Carotid Artery Stenosis Under Local Anaesthesia

Objective To assess changes in cognitive function and affective state following carotid endarterctomy (CEA) for high-degree unilateral internal carotid artery stenosis. Methods In 33 patients, a CEA was performed under local anaesthesia for a high-grade unilateral stenosis of the internal carotid artery (group A). Twenty-five patients underwent surgery for peripheral arterial occlusive disease under regional anaesthesia served as controls (group B). Patients with neurological deficits due to previous strokes or dementia were excluded. Intelligence level was assessed preoperatively. Cognitive tests were applied preoperatively and postoperatively (3–5 days after surgery) and after 4 months follow-up. Confounding factors, including anxiety and depression, were checked through questionnaires and interviews. Results No perioperative neurological complication occurred following CEA. Patients in group A showed a significant postoperative deterioration only in one sub-test. There was no significant change in anxiety and depression during follow up. The control group B had no significant changes in cognitive test performance. Anxiety improved significantly postoperatively, but increased again at the end of the study. There was no significant difference between the groups over time. Conclusion Cognitive function does not change following CEA of a unilateral internal carotid stenosis.

Cognitive Changes 5 Years After Coronary Artery Bypass Grafting

To determine the long-term (preoperative to 5 years postoperative) and late (1-5 years postoperative) changes in cognitive test performance in patients after coronary artery bypass grafting. The departments of surgery and neurology at The Johns Hopkins University School of Medicine, Baltimore, Md. A group of 102 patients who completed preoperative and follow-up cognitive testing up to 5 years after coronary artery bypass grafting. A battery of neuropsychological tests, assessing 8 cognitive domains (attention, language, verbal and visual memory, visuoconstruction, executive function, and psychomotor and motor speed), was administered preoperatively and at 1 month, 1 year, and 5 years postoperatively. Significant changes in neuropsychological test scores from baseline to 5 years were observed in only 3 of the 8 domains: there were declines in visuoconstruction and psychomotor speed and an improvement in executive function. When the period from baseline to 5 years was divided into 2 intervals, we found that cognitive test scores generally improved from baseline to 1 year. By contrast, between 1 and 5 years, there was significant decline in all cognitive domains except for attention and executive function. Some potential explanatory covariates (demographic, medical history, and surgery variables) were associated with changes from baseline to 5 years in some cognitive domains, but few covariates were statistically significant in more than 1 cognitive domain. The change in cognitive test performance between baseline and 5 years is likely related to several factors, including low baseline performance and practice effects. The significant decline in performance between 1 and 5 years, however, raises the possibility that a late cognitive decline may be occurring in this population. Additional studies, with the use of a nonsurgical control group, are needed to determine if the observed cognitive decline is related to bypass surgery itself, normal aging in a population with cardiovascular risk factors, or some combination of these and other factors.