Detailed Neuropsychological Test Battery Research Articles

Importance of individual dietary factors for cognitive performance in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, FINGER

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial that showed beneficial effect on cognition with a 2‐year multidomain lifestyle intervention. One of the four multidomain intervention components was diet and we have earlier shown that overall adherence to the FINGER dietary intervention goals was associated with better cognition. Here our aim is to investigate how the individual components of the dietary adherence score are associated with cognitive performance during the 2‐year period.MethodThe FINGER cohort included 1259 individuals at risk of dementia aged 60‐77 years at baseline, randomized into the multidomain intervention (n = 631) or the control group (n = 628). They underwent extensive data collection annually (total of 3 assessments), including detailed neuropsychological test battery (NTB) and a 3‐day food record. Adherence to dietary intervention was evaluated on 9 items based on dietary recommendations: intake of saturated fat, polyunsaturated fat, sucrose, fiber, protein, alcohol, vegetables, fruits, and fish. Data analyses were completed with mixed‐effects regression.ResultThe goal for low alcohol intake was inversely associated with cognition at baseline, but no other dietary items showed cross‐sectional associations. Reaching the goal for saturated fat, fiber, vegetables, fruits, and fish predicted better cognitive change at two years (p <0.05 for goal*time each). Results were similar when continuous variables rather than dichotomized goals were investigated. Intake of polyunsaturated fats additionally predicted better cognitive change and vegetable intake showed positive cross‐sectional association with cognition. There were no significant interactions with the study group.ConclusionSix out of nine FINGER dietary goals predicted a favorable cognitive change over time, indicating that a dietary pattern adherence with general dietary recommendations is beneficial for brain health. However, alcohol intake goal, i.e. lower alcohol intake, was associated with worse cognition; and cut‐offs for polyunsaturated fats based on the recommendations appeared suboptimal. The FINGER dietary adherence score should be compared with food‐based dietary patterns like Mediterranean Diet to investigate if nutrient intakes should be better taken into account when analyzing diet in relation to cognitive performance.

Impact of the Dopamine System on Long-Term Cognitive Impairment in Parkinson Disease: An Exploratory Study.

Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD). We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD. PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment. Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (P range 0.003-0.005) and higher LEDD over time (P range <0.001-0.01) were significantly associated with increased risk for CI. Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course. Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023).

Association of Income with Post-Stroke Cognition and the Underlying Neuroanatomical Mechanism.

To investigate the association between income and post-stroke cognition at 3 months, and the underlying neuroanatomical mechanism. Patients with first-ever ischemic stroke were enrolled and analyzed. Baseline information on income and neuroimaging measurements with predictive values for post-stroke cognitive impairment (PSCI) were collected within 7 days of the admission. Three months after the index stroke, all participants underwent a detailed neuropsychological test battery. The associations between income and PSCI and between income and brain structural measurements were investigated. A total of 294 patients were recruited for this study. Lower income was independently associated with poor cognitive performance on Stroop tests, Clinical Dementia Rating, Boston Naming Test, and Verbal Fluency Test. Regarding neuroimaging parameters, lower income was associated with a lower total brain volume (TBV)/total intracranial volume (TICV) ratio (p = 0.004). Lower income is associated with an increased chance of post-stroke cognitive decline, particularly in executive function and language domains. Since global brain atrophy (measured by TBV/TICV ratio) is a strong predictor for PSCI, its correlation with income may help explain the neuroanatomical mechanism between income and post-stroke cognition.

Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial

Background: Cognitive impairment affects 50%–75% of people with secondary progressive multiple sclerosis (PwSPMS). Improving our ability to predict cognitive decline may facilitate earlier intervention. Objective: The main aim of this study was to assess the relationship between longitudinal changes in cognition and baseline serum neurofilament light chain (sNfL) in PwSPMS. In a multi-modal analysis, MRI variables were additionally included to determine if sNfL has predictive utility beyond that already established through MRI. Methods: Participants from the MS-STAT trial underwent a detailed neuropsychological test battery at baseline, 12 and 24 months. Linear mixed models were used to assess the relationships between cognition, sNfL, T2 lesion volume (T2LV) and normalised regional brain volumes. Results: Median age and Expanded Disability Status Score (EDSS) were 51 and 6.0. Each doubling of baseline sNfL was associated with a 0.010 [0.003–0.017] point per month faster decline in WASI Full Scale IQ Z-score (p = 0.008), independent of T2LV and normalised regional volumes. In contrast, lower baseline volume of the transverse temporal gyrus was associated with poorer current cognitive performance (0.362 [0.026–0.698] point reduction per mL, p = 0.035), but not change in cognition. The results were supported by secondary analyses on individual cognitive components. Conclusion: Elevated sNfL is associated with faster cognitive decline, independent of T2LV and regional normalised volumes.

Multimodal brain imaging demonstrates that both amyloid burden and glucose metabolism predict the severity of cognitive impairment in patients with Alzheimer’s disease

AbstractBackgroundThe purpose of this study is to assess brain glucose metabolism and Amyloid‐β burden in patients with Alzheimer’s disease with 3 Tesla PET/MR imaging and to seek possible relation of imaging findings with the extent of cognitive impairment.Method45 consecutive subjects with memory complaints were evaluated with a detailed neuropsychological test battery and F18‐Fluorodeoxyglucose(FDG)‐PET/MRI and F18‐Flutemetamol‐PET/MRI scans. The imaging modalities were performed with a hybrid 3T PET / MR camera at a maximum of 7 days intervals. Images were visually evaluated by two nuclear medicine experts. The centiloid scores were calculated through amyloid standardized uptake value ratios (SUVR) for all participants and regional glucose metabolism characteristics were analyzed.ResultThe study population consisted of 30 males and 15 females with a mean age of 65.9±8.2 years. Mean MMSE was 21.7±7.2 for the overall group. Five patients had imaging features suggestive of non‐AD type of dementias and were excluded from further analyses. Visual examination of F18‐Flutemetamol PET/MRI was consistent with the Alzheimer’s disease continuum in 29 cases, 9 of them demonstrated normal glucose metabolism, whereas 20 remaining cases showed F18‐FDG‐PET/MRI patterns characteristic to Alzheimer’s disease (hypometabolism in parieto‐temporal cortices and/or posterior cingulate cortex). In bivariate analysis, MMSE was positively correlated with the glucose metabolism in temporal lobe and posterior cingulate gyrus (r= 0.382, p=0.020; r=0.330, p=0.046; respectively), additionally, a significant negative correlation was observed between MMSE and amyloid burden designated by the centiloid score (r=‐0.461, p=0.004). Memory performance tested by Enhanced Cued Recall (ECR) was also positively associated with the glucose metabolism in posterior cingulate gyrus (r= 0.446, p=0.006), and negatively associated with the centiloid value (r= ‐0.458, p=0.005). The relationship between the ECR test and the centiloid value persisted when adjusted for age, gender, and year of education (β=‐0.121, p=0.021) in multivariate models.ConclusionGeneral cognitive ability and memory were predicted by imaging markers of regional glucose metabolism and amyloid deposition in this study population with early‐stage Alzheimer’s disease. Further research should investigate the predictive value of those imaging markers for the rate of cognitive decline. Acknowledgment: We acknowledge the support of GE Health Care for the [F18]flutemetamol doses.

The effect of intracranial stenosis on cognitive decline in a memory clinic cohort

Intracranial stenosis (ICS) is a risk factor for cognitive impairment and dementia in cross-sectional studies. However, data examining the effect of ICS on cognitive decline is limited. We investigated the effect of ICS on cognition over a period of three years in a memory-clinic cohort. Patients were recruited from the National University Hospital in Singapore. Data was collected using a standardised questionnaire, physical examination and 3T MRI at baseline. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any intracranial vessel. Cognition was measured at baseline and annually for 3 years using the mini-mental state examination, Montreal cognitive assessment, and a detailed neuropsychological test battery. The association between ICS and cognitive decline was analysed using generalized estimating equations. 364 patients were included in the analysis. The mean (±SD) age was 71.9 (±8.0) years and 164 (45.1%) patients were male. A total of 66 (18.1%) patients had ICS. ICS was associated with worse executive function (β:-0.37; [95%CI:-0.68;-0.05]; p=0.022) and modified the effect of follow-up time on memory (p=0.005) and visuomotor speed (p=0.047). These results remained significant after controlling for demographics, overall diagnosis, cardiovascular risk factors, and MRI markers of cerebrovascular disease. ICS was independently associated with worse executive function across all time points, and cognitive decline in memory and visuomotor speed over three-years of follow-up. This suggests that ICS may be a useful indicator of vascular brain damage leading to cognitive decline, and may warrant consideration of anti-atherosclerotic treatment in clinical trials.

Association of early life BMI with dementia risk: Findings from a pooled cohort analysis

AbstractBackgroundThe evidence about the timing and influence of some key cardiovascular risk factors, such as Body Mass Index (BMI), on the risk of Alzheimer disease and other dementias remains debatable. Studies have shown that high midlife BMI increases the risk of dementia, while high late life BMI may be protective; however, relatively little is known about the role of early life BMI on the risk of Alzheimer Disease and other dementias.MethodWe studied 5,104 older adults from two studies, the Cardiovascular Health Study (CHS, n=2,909) and the Health, Aging and Body Composition study (Health ABC, n=2,195) study. For CHS‐Health ABC older adults, we imputed early and midlife BMI, beginning at age 18, using linear mixed models applied to a pooled cohort which also included young and middle‐aged adults from CARDIA and MESA. BMI was then summarized by time‐weighted averages in early (ages 20‐49), mid (ages 50‐69), and late life (ages 70‐89). In CHS, dementia was adjudicated by an expert committee following a detailed neuropsychological test battery and neurological examination. In Health ABC, dementia diagnosis was determined based on hospitalization ICD codes, dementia‐related drugs and decline on the Modified Mini Mental State Examination. All analyses were sex stratified.ResultCHS‐Health ABC participants had a mean age of 72.6 years (SD=4.2) at enrollment, 18% were black and 56% were women. For women, dementia risk increased with higher early life BMI: it was 1.8 times higher among those who were overweight (OR=1.8; 95% CI=1.31‐2.54) and 2.5 times higher among those who were obese (OR=2.45; 95% CI=1.47‐4.06), from pooled logistic regression models adjusted for midlife and late life BMI. For men, dementia risk increased with higher early life (Obese OR=2.47; 95% CI=1.46‐4.19) and mid life BMI (Overweight OR=1.51; 95% CI=1.11‐2.05 and Obese OR=2.00; 95% CI=1.16‐3.42), in models also adjusted for late life BMI. For both women and men, dementia risk decreased with higher late life BMI.ConclusionOur study is the first to report heightened dementia risk with higher early life BMI, for both women and men. Accounting for early life BMI, we found no effect for midlife BMI on dementia risk among women.

Cognitive performance in relation to metabolic disturbances in patients with COPD

Cognitive impairment (CI) and metabolic abnormalities, including the metabolic syndrome (MetS) and sarcopenia, are more prevalent in COPD patients compared to controls without diagnosed lung disease. Because earlier studies have shown these metabolic abnormalities may affect cognitive performance, this study investigated whether cognitive performance is more impaired in subgroups of COPD patients with MetS or sarcopenia. Cognitive performance patterns of 170 COPD patients referred for pulmonary rehabilitation (53.5% male, 63.4±9.4 years, FEV1 54.5±22.7% predicted) were compared between COPD subgroups stratified by presence of MetS and sarcopenia. Cognitive performance was assessed using a detailed neuropsychological test battery, which measured psychomotor speed (Stroop Color-Word Test, Concept Shifting Test, Letter-Digit Substitution Test), planning (Behavioral Assessment of the Dysexecutive Syndrome), working memory (Visual-Verbal Learning Test, Digit Span), verbal memory (Visual-Verbal Learning Test) and cognitive flexibility (Stroop Color-Word Test, Concept Shifting Test). MetS was determined according to the NCEP ATP-III criteria. Sarcopenia was determined based on decreased appendicular lean mass by dual-energy x-ray absorptiometry and impaired physical performance by 6-min walking distance. MetS was observed in 54.7% and sarcopenia in 30.0% of COPD patients. The prevalence of general CI was not different between patients with and without MetS (30.4% and 39.0%, respectively) or those with and without sarcopenia (34.0% and 34.5%, respectively, both p>0.05). Domain-specific cognitive performance was not different between metabolic subgroups, but those with sarcopenia displayed a lower prevalence of CI on verbal memory than those without (21.7% and 29.7%, respectively, p=0.011). Only the digit span (working memory) subtest was significantly different between metabolic subgroups, in favor of those without MetS (p=0.017). Cognitive performance was not affected more in COPD patients with sarcopenia or MetS.

Validation of a German version of the Cerebellar Cognitive Affective/ Schmahmann Syndrome Scale: preliminary version and study protocol

BackgroundTraditionally, cerebellar disorders including ataxias have been associated with deficits in motor control and motor learning. Since the 1980’s growing evidence has emerged that cerebellar diseases also impede cognitive and affective processes such as executive and linguistic functions, visuospatial abilities and regulation of emotion and affect. This combination of non-motor symptoms has been named Cerebellar Cognitive Affective/ Schmahmann Syndrome (CCAS). To date, diagnosis relies on non-standardized bedside cognitive examination and, if available, detailed neuropsychological test batteries. Recently, a short and easy applicable bedside test (CCAS Scale) has been developed to screen for CCAS. It has been validated in an US-American cohort of adults with cerebellar disorders and healthy controls. As yet, the CCAS Scale has only been available in American English. We present a German version of the scale and the study protocol of its ongoing validation in a German-speaking patient cohort.MethodsA preliminary German version has been created from the original CCAS Scale using a standardized translation procedure. This version has been pre-tested in cerebellar patients and healthy controls including medical experts and laypersons to ensure that instructions are well understandable, and that no information has been lost or added during translation. This preliminary German version will be validated in a minimum of 65 patients with cerebellar disease and 65 matched healthy controls. We test whether selectivity and sensitivity of the German CCAS Scale is comparable to the original CCAS Scale using the same cut-off values for each of the test items, and the same pass/ fail criteria to determine the presence of CCAS. Furthermore, internal consistency, test-retest and interrater reliability will be evaluated. In addition, construct validity will be tested in a subset of patients and controls in whom detailed neuropsychological testing will be available. Secondary aims will be examination of possible correlations between clinical features (e.g. disease duration, clinical ataxia scores) and CCAS scores.PerspectiveThe overall aim is to deliver a validated bedside test to screen for CCAS in German-speaking patients which can also be used in future natural history and therapeutic trials.Study registrationThe study is registered at the German Clinical Study Register (DRKS-ID: DRKS00016854).

Electrophysiological and neuropsychological outcomes of severe obstructive sleep apnea: effects of hypoxemia on cognitive performance.

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized with upper airway obstructions. Some studies showed cognitive and electrophysiological changes in patients with OSAS; however, contradictory results were also reported. The purpose of the present study was twofold: (1) to investigate cognitive changes in severe OSAS patients by using neuropsychological tests and electrophysiological methods together, (2) to investigate influence of hypoxemia levels on cognition. Fifty-four severe OSAS patients and 34 age-, gender- and education matched healthy subjects were participated. OSAS patients were further divided into two subgroups according to minimum oxygen saturation levels. All participants underwent a detailed neuropsychological test battery. A classical visual oddball task was used to elicit ERP P300 and mean P300 amplitudes were measured from Fz, Cz and Pz electrode sites. OSAS patients showed reduced mean P300 amplitudes up to 43-51% on all electrode sites compared to healthy controls. Subgroup analysis revealed significant differences in neuropsychological test scores between healthy controls and high hypoxemia OSAS group, as well as between low and high hypoxemia groups. Moreover, both low and high hypoxemia OSAS groups had lower P300 amplitudes compared with healthy controls. P300 amplitudes showed a gradual decline in parallel with increasing hypoxemia severity; however, the difference between high and low hypoxemia OSAS groups did not reach significance. Moderate correlations were found between sleep parameters, neuropsychological test scores and P300 amplitudes. These results suggest that electrophysiological measures could be better indicators of cognitive changes than neuropsychological tests in OSAS, particularly in mildly affected patients.

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

Cognitive screening among acute respiratory failure survivors: a cross-sectional evaluation of the Mini-Mental State Examination

IntroductionThe Mini-Mental State Examination (MMSE) is a common cognitive screening test, but its utility in identifying impairments in survivors of acute respiratory failure is unclear. The purpose of this study was to evaluate MMSE performance versus a concurrently administered detailed neuropsychological test battery in survivors of acute respiratory failure.MethodsThis cross-sectional analysis used data from the ARDSNet Long Term Outcomes Study (ALTOS) and Awakening and Breathing Controlled Trial (ABC). Participants were 242 survivors of acute respiratory failure. The MMSE and detailed neuropsychological tests were administered at 6 and 12 months post-hospital discharge for the ALTOS study, and at hospital discharge, 3 and 12 months for the ABC study. Overall cognitive impairment identified by the MMSE (score <24) was compared to impairments identified by the neuropsychological tests. We also matched orientation, registration, attention, memory and language domains on the MMSE to the corresponding neuropsychological test. Pairwise correlations, sensitivity, specificity, positive and negative predictive values, and agreement were assessed.ResultsAgreement between MMSE and neuropsychological tests for overall cognitive impairment was fair (42 to 80%). Specificity was excellent (≥93%), but sensitivity was poor (19 to 37%). Correlations between MMSE domains and corresponding neuropsychological tests were weak to moderate (6 months: r = 0.11 to 0.28; 12 months: r = 0.09 to 0.34). The highest correlation between the MMSE and neuropsychological domains was for attention at 6 months (r = 0.28) and language at 12 months (r = 0.34).ConclusionsIn acute respiratory failure survivors, the MMSE has poor sensitivity in detecting cognitive impairment compared with concurrently administered detailed neuropsychological tests. MMSE results in this population should be interpreted with caution.

The Montreal Cognitive Assessment (MoCA) - a sensitive screening instrument for detecting cognitive impairment in chronic hemodialysis patients.

BackgroundChronic kidney disease (CKD) patients undergoing hemodialysis (HD) therapy have an increased risk of developing cognitive impairment and dementia, which are known relevant factors in disease prognosis and therapeutic success, but still lack adequate screening in clinical routine. We evaluated the Montreal Cognitive Assessment (MoCA) for suitability in assessing cognitive performance in HD patients in comparison to the commonly used Mini-Mental State Examination (MMSE) and a detailed neuropsychological test battery, used as gold standard.Methods43 HD patients and 42 healthy controls with an average age of 58 years, were assessed with the MoCA, the MMSE and a detailed neuropsychological test battery, covering the domains of memory, attention, language, visuospatial and executive functions. Composite scores were created for comparison of cognitive domains and test results were analyzed using Spearman's correlation and linear regression. Cognitive dysfunction was defined using z-score values and predictive values were calculated. Sensitivity and specificity of the MoCA were determined using receiver operating characteristic (ROC) analysis.ResultsHD patients performed worse in all cognitive domains, especially in memory recall and executive functions. The MoCA correlated well with the detailed test battery and identified patients with cognitive impairment with a sensitivity of 76.7% and specificity of 78.6% for a cut-off value of ≤24 out of 30 points. In the detailed assessment executive functions accounted significantly for performance in the MoCA. The MMSE only discriminated weakly between groups.ConclusionsThe MoCA represents a suitable cognitive screening tool for hemodialysis patients, demonstrating good sensitivity and specificity levels, and covering executive functions, which appear to play an important role in cognitive performance of HD patients.

Interaction of BDNF and COMT Polymorphisms on Paired-Associative Stimulation-Induced Cortical Plasticity

The common single-nucleotide polymorphism (SNP) brain-derived neurotrophic factor (BDNF) valine-to-methionine substitution at codon 66 (Val66Met) has been associated with differences in memory functions and cortical plasticity following brain stimulation. Other studies could not confirm these results, though, and potential interactions of BDNF carrier status with other learning-relevant SNPs are largely unknown. The present study aimed to evaluate the effects of BDNF Val66Met genotype on paired associative stimulation (PAS)-induced motor cortex plasticity, while additionally taking catechol-O-methyltransferase (COMT) Val158Met and kidney and brain (KIBRA) rs17070145 carrier status into account. Therefore, a cohort of 2 × 16 age- and education-matched healthy young females underwent transcranial magnetic stimulation using an excitatory PAS(25) protocol to induce cortical plasticity. Cognitive performance was assessed using implicit grammar- and motor-learning tasks and a detailed neuropsychological test battery. While BDNF carrier status alone did not significantly influence PAS-induced cortical plasticity, we found a significant BDNF × COMT interaction, showing higher plasticity immediately following the PAS(25) protocol for the BDNF Val/Val vs Met genotype in COMT Met homozygotes only (ANOVA, p = 0.027). A similar advantage for this group was noted for implicit grammar learning (ANOVA, p = 0.021). Accounting for KIBRA rs17070145 did not explain significant variance. Our findings for the first time demonstrate an interaction of BDNF by COMT on human cortical plasticity. Moreover, they show that genotype-related differences in neurophysiology translate into behavioral differences. These findings might contribute to a better understanding of the mechanisms of interindividual differences in cognition.

Cognitive correlates of “neglect-like syndrome” in patients with complex regional pain syndrome

Patients with complex regional pain syndrome (CRPS) often show distinct neurocognitive dysfunctions, which were initially termed “neglect-like symptoms.” So far, particularly the patients’ feelings about the affected extremity, motor, and sensory aspects of the “neglect-like symptoms” have been investigated, possibly pointing to a disturbed body schema. Because patients with classical neurological neglect show diminished awareness regarding the perception of their body, as well as of the space around them, our hypothesis was that CRPS patients exhibit some signs of personal neglect and extrapersonal visuospatial problems over and beyond those seen in patients simply suffering from limb pain. We used quantitative sensory testing and motor assessment aimed at detecting motor and sensory loss, a standardized questionnaire calculating a neglect score, and applied a detailed neuropsychological test battery assessing different parietal lobe functions, including visual neglect. We examined 20 CRPS patients and 2 matched control groups, one consisting of healthy subjects and the other one of patients with limb pain other than CRPS. Results show significant higher neglect scores for CRPS patients and the pain control group, but interestingly, CRPS patients and pain patients were indistinguishable. The results of the neuropsychological test battery did not demonstrate systematic variances, which would be indicative of a classical neurological neglect in CRPS patients, even though there were 3 CRPS patients who differed ⩾2 SD from the mean of our healthy control group, with poorer results in ⩾3 different tests. We assume that the “neglect-like syndrome” in most CRPS patients is different from typical neglect.

Factors affecting brain structure in men with HIV disease in the post-HAART era

The purpose of this study was to characterize brain volumetric differences in HIV seropositive and seronegative men and to determine effects of age, cardiovascular risk, and HIV infection on structural integrity. Magnetic resonance imaging was used to acquire high-resolution neuroanatomic data in 160 men aged 50years and over, including 84 HIV seropositive and 76 seronegative controls. Voxel-based morphometry was used to derive volumetric measurements at the level of the individual voxel. Data from a detailed neuropsychological test battery were recombined into four summary scores representing psychomotor speed, visual memory, verbal memory, and verbal fluency. Both age and HIV status had a significant effect on both gray matter (GM) and white matter (WM) volume. The age-related GM atrophy was primarily in the superior temporal and inferior frontal regions; the HIV-related GM loss included the posterior and inferior temporal lobes, the parietal lobes, and the cerebellum. Among all subjects, the performance on neuropsychological tests, as indexed by a summary variable, was related to the volume of both the GM and WM. Contrary to our predictions, the CVD variables were not linked to brain volume in statistically adjusted models. In the post-HAART era, having HIV infection is still linked to atrophy in both GM and WM. Secondly, advancing age, even in this relatively young cohort, is also linked to changes in GM and WM volume. Thirdly, CNS structural integrity is associated with overall cognitive functions, regardless of the HIV infection status of the study volunteers.

Validity of the International HIV Dementia Scale in South Africa

HIV-associated neurocognitive disorders (HAND) remain prevalent, especially in regions like South Africa where HIV prevalence is high but access to antiretroviral treatment (ART) is limited. The incidence of HIV dementia (HAD) has been halved with the use of ART, but the prevalence remains high. Appropriate brief screening tools to screen for HAD are needed in order to facilitate treatment initiation. The validity of the International HIV Dementia Scale has not been established in a region where infection with HIV clade C is predominant. The International HIV Dementia Scale (IHDS) was administered together with a detailed neuropsychological test battery to 96 HIV-positive individuals who had not received ART and who were attending primary care HIV clinics. The validity of the IHDS was established using a receiver operating characteristic (ROC) analysis. HIV-positive individuals displayed greater impairment when compared to HIV-negative controls on the IHDS and a range of neuropsychological tests. Neuropsychological tests discriminated well across HAND categories for HIV-positive individuals. In ROC analysis, the IHDS showed an area under the curve of 0.64, with a sensitivity of 45% and specificity of 79% at a cutoff score of 10. Individuals with HAD, who screened negative on the IHDS, performed poorly on some tests of executive function. These data suggest that the IHDS may have limitations as a tool to screen for HAD in South Africans infected with HIV. Variable performance in neuropsychological testing may account for false negative screens. The inclusion of brief tests of executive function in a screening battery should be considered.

Cognitive deficits in relation to personality type and hypothalamic‐pituitary‐adrenal (HPA) axis dysfunction in women with stress‐related exhaustion

Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26-53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.

Single and Combined Effects of Cerebral White Matter Lesions and Lacunar Infarctions on Cognitive Function in an Elderly Population

This study is to investigate the association between single and combined vascular brain changes (white matter lesions [WMLs], lacunar infarctions) and the cognitive domains of memory, processing speed, and motor function in the elderly adults. In a sample of 268 participants aged 65-83 years of the MEMO (Memory and Morbidity in Augsburg Elderly) population-based study in Augsburg, Germany, cerebral magnetic resonance imaging (MRI) was performed and a detailed neuropsychological test battery applied. Analysis of covariance determined the effects of vascular brain changes on domains of cognitive functioning. Strong associations of large WMLs and of MRI-defined lacunar infarction with three different domains of cognitive function even after adjustment for age, gender, and education were found. The combined occurrence of both lesions affected about one in 10 participants and was associated with a strong decrease in cognitive function in all domains. The difference between the groups with only one lesion type (either large WMLs or MRI-defined infarction) and participants affected by both was significant in the domains of processing speed and memory, even after adjustment for important confounders such as age, gender, education, and comorbidities. The effects of both lesion types on cognitive function were not more than additive. Our study shows that both large WMLs and MRI-defined lacunar infarction contribute to impairments in different cognitive domains. The results suggest that their combined occurrence is associated with stronger reductions in cognitive function than each of the two brain lesion types alone.

Cognitive Impairment No Dementia – Neuropsychological and Neuroimaging Characterization of an Amnestic Subgroup

Background/Aims: Cognitive impairment no dementia (CIND) describes individuals whose cognitive functioning falls below normal but who do not meet dementia criteria. An important goal within CIND is to identify subgroups that will predictably progress to Alzheimer disease. CIND with amnestic deficits has been associated with high risk of Alzheimer disease but has until now been investigated on a retrospective basis. In this study a prospectively defined amnestic CIND group was characterized on a detailed neuropsychological test battery and on structural magnetic resonance imaging (MRI) measures. Methods: Amnestic CIND was defined as meeting at least 1 but not all DSM-IV-TR criteria for dementia, scoring ≧1 SD below norms on Rey Auditory Verbal Learning Test delayed recall, having a Clinical Dementia Rating score of 0.5 and a Mini-Mental State Exam score ≧24. This cross-sectional study compared subjects meeting these criteria (n = 25) to age- and education-matched controls (n = 26). The neuropsychological battery included memory and nonmemory measures that were analyzed as continuous variables and dichotomized into impaired (≧1 SD below controls) versus nonimpaired. MRI scans were evaluated with a global-brain volumetric measure [brain fractional ratio (BFR)] and with visually based medial temporal lobe atrophy (MTA) ratings. Results: Amnestic CIND had neuropsychological impairment in the episodic memory domain and also in nonmemory domains. There were 80% of CIND subjects with multidomain impairment. The most clear-cut nonmemory impairment was in the verbal ability domain, with 64% of subjects affected and a moderate effect size (d = 0.7). On MRI, BFR was lower (74.5 ± 4.6 vs. 75.5 ± 4.4) and MTA higher (72 vs. 38% with MTA ≧1) in CIND than in control subjects. BFR correlated with MTA (r = –0.45) and with a composite memory score (r = 0.296). Conclusion: A prospective amnestic CIND grouping appears to identify individuals with a multidomain pattern of neuropsychological impairment and with both medial temporal lobe and global brain atrophy.