Higher Verbal Fluency Research Articles

Dairy intake and cognitive function in older adults in three cohorts: a mendelian randomization study.

Meta-analyses of observational studies on the effect of dairy on cognitive function have yielded inconclusive results, potentially due to unmeasured confounding. To avoid the no-unmeasured confounding assumption, we used lactase persistence genetic variant as an instrumental variable, for which the CC genotype is associated with lower lactase production and, consequently, lower dairy consumption. We used it to assess the effect of long-term consumption of total and non-fermented dairy on cognitive function. We included 43,836 individuals over 55 years old with genotyping, dietary data, and cognitive function measurements from three population-based studies: CoLaus|PsyCoLaus (Switzerland), the Rotterdam Study (the Netherlands) and the Canadian Longitudinal Study on Aging (CLSA - Canada). We performed a one-sample Mendelian randomization using two-stage least-squares regression. First, we estimated total and non-fermented dairy consumption by T-allele frequency. Second, we used the estimated dairy consumption in linear regression models on general cognition, assessed by the Mini-Mental State Examination (MMSE) and the Mental Alternation Test, executive function, verbal fluency, verbal learning, and memory. Per T-allele, total dairy intake and non-fermented was 24.8 and 15.3g/day higher in PsyCoLaus, 57.9 and 49.8g/day in the Rotterdam Study, and 0.31 and 0.29 times/day in CLSA, respectively. We found no association between the genetically predicted difference and the MMSE in PsyCoLaus and the Rotterdam Study. However, lactase persistent individuals scored 3.4 (95% CI2.1- 4.7) and 3.5 (95% CI 2.3-4.7) points more in the Mental Alternation Test for total and fermented dairy, respectively, in CLSA. Similarly, lactase persistent participants in CLSA had higher verbal fluency, verbal learning and executive function, but no differences were found in the other cohorts. Such inconsistencies might stem from different FFQs across cohorts and consumption ranges. Nonetheless, the generally small magnitude of effect sizes may suggest that there is no real effect between total or non-fermented dairy intake and cognitive function. The evidence for a causal effect of dairy consumption on general cognitive function is weak, consistent with previous results from classic analysis from observational studies. Interventions targeting dairy are unlikely to have a relevant effect on cognitive function.

Social health and subsequent cognitive capability: examining the potential mediating roles of depression symptoms and inflammatory biomarkers

AbstractBackgroundSocial health (SH) markers, including marital status, contact frequency, network size, and social support, have been linked with increased cognitive capability. However, the underlying mechanisms remain poorly understood. We aim to investigate whether depression symptoms and inflammatory biomarkers mediate associations between SH and cognitive outcomes.MethodWe used data from waves 1‐9 of the English Longitudinal Study of Ageing, involving 7,136 participants aged 50 or older at baseline. First, we examined associations between SH (wave 1) and depression and inflammatory biomarkers (C‐reactive protein (CRP) and fibrinogen) (wave 2) using linear regression models. Second, we tested associations between a) SH and b) depression and inflammation with subsequent standardised verbal fluency and memory in wave 3 and change between waves 3‐9, indexed using slopes derived from multilevel models. We adjusted for age, sex, socio‐economic position, cardiovascular disease, basic and instrumental activities of daily living, health behaviours, and baseline depression symptoms and cognition. We will also conduct causal mediation analysis.ResultAll SH markers, except contact frequency, were associated with lower subsequent depression, but not inflammatory biomarkers. Greater contact frequency (e.g. once‐twice a week vs <once per year: β = 0.18 [0.01, 0.36]) and less negative support (β = 0.02 [0.00, 0.03]) were associated with higher verbal fluency. Larger network size (>6 people vs none: β = 0.007SD/year [0.001, 0.012]), less negative (β = 0.001SD/year [0.001, 0.002]) and more positive support (β = 0.001SD/year [0.000, 0.001]) were linked with slower memory decline, and more positive support predicted slower verbal fluency decline (β = 0.001SD/year [0.000, 0.001]). Depression symptoms were associated with lower memory and verbal fluency, and faster memory decline (β = ‐0.001SD/year [‐0.001, ‐0.000]) and verbal fluency (β = ‐0.001SD/year [‐0.001, ‐0.000]). CRP was associated with lower verbal fluency (β = ‐0.02 [‐0.04, 0.00]), whereas fibrinogen was linked with faster memory decline (β = ‐0.001SD/year [‐0.003, ‐0.000]).ConclusionDepression symptoms and SH showed associations with subsequent cognitive capability and change. SH was linked with lower depression, but not inflammatory biomarkers. Findings highlight the potential for depression to underpin associations between SH and cognition, a pathway which we will test using causal mediation analysis. We will also examine whether findings replicate in the Swedish National Study of Aging and Care in Kungsholmen.

FC40: Social health and subsequent cognitive capability: examining the potential mediating roles of depression symptoms and inflammatory biomarker

Objective:Social health (SH) markers, including marital status, contact frequency, network size, and social support, have been linked with increased cognitive capability. However, the underlying mechanisms remain poorly understood. We aim to investigate whether depression symptoms and inflammatory biomarkers mediate associations between SH and cognitive outcomes.Methods:We used data from waves 1-9 of the English Longitudinal Study of Ageing, involving 7,136 participants aged 50 or older at baseline. First, we examined associations between SH (wave 1) and depression and inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) (wave 2) using linear regression models. Second, we tested associations between a) SH and b) depression and inflammation with subsequent standardised verbal fluency and memory in wave 3 and change between waves 3-9, indexed using slopes derived from multilevel models. We adjusted for age, sex, socio-economic position, cardiovascular disease, basic and instrumental activities of daily living, health behaviours, and baseline depression symptoms and cognition. We will also conduct causal mediation analysis.Results:All SH markers, except contact frequency, were associated with lower subsequent depression, but not inflammatory biomarkers. Greater contact frequency (e.g. once-twice a week vs <once per year: β=0.18 [0.01, 0.36]) and less negative support (β=0.02 [0.00, 0.03]) were associated with higher verbal fluency. Larger network size (>6 people vs none: β=0.007SD/year [0.001, 0.012]), less negative (β=0.001SD/year [0.001, 0.002]) and more positive support (β=0.001SD/year [0.000, 0.001]) were linked with slower memory decline, and more positive support predicted slower verbal fluency decline (β=0.001SD/year [0.000, 0.001]). Depression symptoms were associated with lower memory and verbal fluency, and faster memory decline (β=-0.001SD/year [-0.001, -0.000]) and verbal fluency (β=-0.001SD/year [-0.001, -0.000]). CRP was associated with lower verbal fluency (β=-0.02 [-0.04, 0.00]), whereas fibrinogen was linked with faster memory decline (β=-0.001SD/year [-0.003, -0.000]).Conclusion:Depression symptoms and SH showed associations with subsequent cognitive capability and change. SH was linked with lower depression, but not inflammatory biomarkers. Findings highlight the potential for depression to underpin associations between SH and cognition, a pathway which we will test using causal mediation analysis. We will also examine whether findings replicate in the Swedish National Study of Aging and Care in Kungsholmen.

Accelerometer-Measured Sedentary Behavior Patterns, Brain Structure, and Cognitive Function in Dementia-Free Older Adults: A Population-Based Study.

Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood. To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms. This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models. In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores. Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.

Limited connectedness of spontaneous speech may be a marker of dementia due to Alzheimer's disease.

The study evaluated the connectedness of spontaneous speech production in individuals with dementia as a potential predictor of dementia severity. Data were derived from the baseline sample of 143 individuals with dementia in the English Pitt corpus. Dementia severity was assessed via the Mini Mental Status Exam, the Mattis Dementia Rating Scale, and the Blessed Dementia Scale. Language abilities were evaluated using verbal fluency and picture description tasks. Graph analysis was carried out for the picture description task using the computational tool SpeechGraphs to calculate connectedness. Results demonstrated that higher educational attainment, higher verbal fluency and strongly-connected spontaneous speech were associated with better cognitive function. Results suggest that automated language processing approaches, such as graph structure analysis, may provide a faster and ecologically valid method of detecting dementia symptoms.

Performance and exploration of ChatGPT in medical examination, records and education in Chinese: Pave the way for medical AI

BackgroundAlthough chat generative pre-trained transformer (ChatGPT) has made several successful attempts in the medical field, most notably in answering medical questions in English, no studies have evaluated ChatGPT's performance in a Chinese context for a medical task. ObjectiveThe aim of this study was to evaluate ChatGPT’s ability to understand medical knowledge in Chinese, as well as its potential to serve as an electronic health infrastructure for medical development, by evaluating its performance in medical examinations, records, and education. MethodThe Chinese (CNMLE) and English (ENMLE) datasets of the China National Medical Licensing Examination and the Chinese dataset (NEEPM) of the China National Entrance Examination for Postgraduate Clinical Medicine Comprehensive Ability were used to evaluate the performance of ChatGPT (GPT-3.5 and GPT-4). We assessed answer accuracy, verbal fluency, and the classification of incorrect responses owing to hallucinations on multiple occasions. In addition, we tested ChatGPT's performance on discharge summaries and group learning in a Chinese context on a small scale. ResultsThe accuracy of GPT-3.5 in CNMLE, ENMLE, and NEEPM was 56% (56/100), 76% (76/100), and 62% (62/100), respectively, compared to that of GPT-4, which was of 84% (84/100), 86% (86/100), and 82% (82/100). The verbal fluency of all the ChatGPT responses exceeded 95%. Among the GPT-3.5 incorrect responses, the proportions of open-domain hallucinations were 66 % (29/44), 54 % (14/24), and 63 % (24/38), whereas close-domain hallucinations accounted for 34 % (15/44), 46 % (14/24), and 37 % (14/38), respectively. By contrast, GPT-4 open-domain hallucinations accounted for 56% (9/16), 43% (6/14), and 83% (15/18), while close-domain hallucinations accounted for 44% (7/16), 57% (8/14), and 17% (3/18), respectively. In the discharge summary, ChatGPT demonstrated logical coherence, however GPT-3.5 could not fulfill the quality requirements, while GPT-4 met the qualification of 60% (6/10). In group learning, the verbal fluency and interaction satisfaction with ChatGPT were 100% (10/10). ConclusionChatGPT based on GPT-4 is at par with Chinese medical practitioners who passed the CNMLE and at the standard required for admission to clinical medical graduate programs in China. The GPT-4 shows promising potential for discharge summarization and group learning. Additionally, it shows high verbal fluency, resulting in a positive human–computer interaction experience. GPT-4 significantly improves multiple capabilities and reduces hallucinations compared to the previous GPT-3.5 model, with a particular leap forward in the Chinese comprehension capability of medical tasks. Artificial intelligence (AI) systems face the challenges of hallucinations, legal risks, and ethical issues. However, we discovered ChatGPT's potential to promote medical development as an electronic health infrastructure, paving the way for Medical AI to become necessary.

Slow information processing speed elucidates impairment in executive function tests in people with Multiple Sclerosis (P13-3.008)

<h3>Objective:</h3> Analyze the association between performance on speeded and nonspeeded tasks of executive functions (EFs) and slow information processing speed (IPS) in people with Multiple Sclerosis (PwMS). <h3>Background:</h3> IPS and EFs are impaired domains in PwMS. However, it is unclear if executive deficits can be explained by slow IPS. <h3>Design/Methods:</h3> 74 PwMS were included (RR=86.2%, PP=4.3%, SP=9.6%; 74% female; age: 46.12±12.48 years; Physical disability (EDSS): 3.60±2.57; disease duration: 14.85±10.69 years). Measures: IPS: Symbol Digit Modalities Test; EFs: Speeded task of cognitive flexibility (Verbal Fluency), nonspeeded task of cognitive flexibility (Brixton Spatial Anticipation Test), nonspeeded task of working memory (Verbal Backward Digit Span); Clinical variables: EDSS, Fatigue Severity Scale and Beck Depression Inventory-II. A probit regression was performed, the results are shown in predicted probabilities format. <h3>Results:</h3> 47% of PwMS have slow IPS. IPS was associated with EDSS and all EFs measures (<i>p</i>=0.00) and did not correlated with fatigue and depression (<i>p</i>&gt;0.05). For the regression model, IPS, EDSS and EFs tasks were analyzed. Brixton and backward span tests lost significance when physical disability was controlled. Finally, the regression model had verbal fluency (Coefficient:-.49;<i>p</i>=0.001) and physical disability (Coefficient:.21; <i>p</i>=0.02) as independent variables. R²28%. Prob.chi2=0.00. For the predicted probabilities, verbal fluency was divided into 4 groups, controlling physical disability, and it was found that the probability of having poor verbal fluency with poor IPS is very high in the 1st and 2nd groups (.89 and .68, lowest confidence interval 0.53) and the probability of having high verbal fluency and slow IPS is very low in the 3th and 4th groups (.38 and .14, highest confidence interval 0.50), with no overlapping confidence intervals. Correctly classified 72%. <h3>Conclusions:</h3> Impairments on speeded task of EFs can be associated with slow IPS. It is important to include speeded and unspeeded tasks in the assessment of EFs to capture the effective deficit. <b>Disclosure:</b> Maria Sol Román has nothing to disclose. Miss Bardoneschi has nothing to disclose. Ms. Gatti has nothing to disclose. Mrs. De Los Santos has nothing to disclose. Mr. Iglesias Passada has nothing to disclose. Miss Daniele has nothing to disclose. Maria Laura Saladino has nothing to disclose. Fernando Caceres has nothing to disclose. Sandra Vanotti has received research support from Merck S.A.,Buenos Aires, Argentina, an affiliate Merck S.A.,Buenos Aires, Argentina, an affiliate of Merck KGaA, Darmstadt, Germany Merck KGaA, Darmstadt, Germany.

Sex Differences in Social Cognition and Association of Social Cognition and Neurocognition in Early Course Schizophrenia.

BackgroundBoth impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia.MethodsIn this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed using t-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology.ResultsNo sex differences were found in ToM (p = 0.071) or hostility bias (p = 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p < 0.01), whereas higher executive function was significantly associated with higher ToM in males (p < 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p < 0.05), whereas neurocognition and hostility bias were not significantly associated in males.ConclusionThe results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

Neuropsychological assessment of patients with alzheimer’s Disease in the presence or absence of spouses

A common question in the neuropsychological testing of patients with Alzheimer’s Disease is whether or not patients should be tested in the presence of their spouses. We addressed this issue by assessing the neuropsychological performances of Alzheimer’s Disease patients in the presence or absence of spouses. Results showed no significant differences between patients’ performances in the presence or absence of spouses on tests assessing general cognitive abilities, episodic memory, working memory, inhibition and flexibility. No significant differences were observed regarding either anxiety or depression in patients when tested alone, compared to when spouses were attending. However, patients demonstrated higher verbal fluency when tested alone compared to when spouses attended. Clinicians may carry out neuropsychological assessment in the presence or absence of spouses, except when assessing verbal fluency. In such cases, clinicians should privilege testing patients alone or, if spouses attend the test, take into account this variable when interpreting patients’ performances.

Crosslinguistic Influence in the Discrimination of Korean Stop Contrast by Heritage Speakers and Second Language Learners

The present study examines the extent of crosslinguistic influence from English as a dominant language in the perception of the Korean lenis–aspirated contrast among Korean heritage speakers in the United States (N = 20) and English-speaking learners of Korean as a second language (N = 20), as compared to native speakers of Korean immersed in the first language environment (N = 20), by using an AX discrimination task. In addition, we sought to determine whether significant dependencies could be observed between participants’ linguistic background and experiences and their perceptual accuracy in the discrimination task. Results of a mixed-effects logistic regression model demonstrated that heritage speakers outperformed second language learners with 85% vs. 63% accurate discrimination, while no significant difference was detected between heritage speakers and first language-immersed native speakers (85% vs. 88% correct). Furthermore, higher verbal fluency was significantly predictive of greater perceptual accuracy for the heritage speakers. The results are compatible with the interpretation that the influence of English on the discrimination of the Korean laryngeal contrast was stronger for second language learners of Korean than for heritage speakers, while heritage speakers were not apparently affected by dominance in English in their discrimination of Korean lenis and aspirated stops.

Cognitive functioning in ultra-high risk for psychosis individuals with and without depression: Secondary analysis of findings from the NEURAPRO randomized clinical trial

Neurocognitive impairments are well established in both ultra-high risk (UHR) for psychosis and major depressive disorder (MDD). Despite this understanding, investigation of neurocognitive deficits in UHR individuals with MDD and its association with MDD within this population, has been scarce. Hence, this study aimed to examine any differences in neurocognition at baseline between those with MDD at baseline and those with no history of MDD, as well as determine whether neurocognitive variables are significantly associated with meeting criteria for MDD at follow-up, while controlling for relevant clinical variables, within a UHR cohort. Data analysis was conducted on 207 participants whose baseline neurocognition was assessed using Brief Assessment of Cognition for Schizophrenia, as part of a trial of omega-3 fatty acids (NEURAPRO) for UHR individuals. While baseline MDD was the strongest predictor, poorer verbal memory and higher verbal fluency were significantly associated with MDD at 12 months (p = .04 and 0.026, respectively). Further, higher processing speed was significantly associated with MDD at medium-term follow-up (p = .047). These findings outline that neurocognitive skills were independently associated with meeting criteria for MDD at follow-up within UHR individuals, with novel findings of better verbal fluency and processing speed being linked to MDD outcomes. Hence, neurocognitive performance should be considered as a marker of risk for MDD outcomes and a target for management of MDD in UHR.

Age-related changes in processing speed modulate context use during idiomatic ambiguity resolution

ABSTRACTThe goal of the current study was to investigate whether age-related changes in processing speed, as indexed by verbal fluency, modulate context use in the resolution of ambiguous idioms (e.g., tie the knot). Younger and older adults completed a cross-modal priming experiment where they decided whether visual word targets were related in meaning to idiomatically or literally biased auditory sentence primes. Older adults with high verbal fluency, similar to younger adults, showed context-dependent facilitation in both biasing sentence contexts. In contrast, older adults with low verbal fluency did not show facilitation of literal meanings in literally biased sentence contexts, likely because they had difficultly inhibiting the dominant figurative meaning. These findings argue that age-related changes in context use during ambiguity resolution are restricted to older adults with reduced processing speed. The results also suggest that verbal fluency may reflect the speed in recruiting frontally-mediated selection mechanisms during ambiguity resolution.

Association of neurocognitive deficits and insight in schizophrenia.

To evaluate the relationship between neurocognitive deficits and insight (clinical & cognitive) among patients with schizophrenia in clinical remission. 60 patients with schizophrenia (diagnosed as per the DSM-IV criteria) in clinical remission were assessed on Beck Cognitive Insight scale (BCIS), Positive and Negative symptom scale (PANSS) and neurocognitive battery (Trail A and B, Stroop Test, Controlled Oral Words Association (COWA) and Tower of London (TOL). Lower processing speed, low cognitive flexibility and poor executive functions as assessed by Trail A, Trail B and TOL respectively and higher verbal fluency (COWA) were associated with poor cognitive insight in the self-certainty domain. Poor executive functioning (3 moves problem of TOL) was associated with lower cognitive insight in the domain of self-reflectiveness. Clinical insight as assessed by item number 12 of general psychopathology subscale of PANSS did not have any association with any of the neurocognitive domains except for few subsets of executive functions as assessed by TOL. There was no correlation between clinical insight and cognitive insight. However, many of these correlations were weak and could be due to Type-1 error as significance of correlation was fixed at two tailed 0.05 level. Multiple regression analysis demonstrated cognitive flexibility as assessed by Trail B test and executive functions (3 moves and 5 moves problems of TOL) to be the significant predictors of self-certainty and self- reflectiveness domains of the cognitive insight. The present study suggests that poor cognitive flexibility and executive dysfunction are associated with poor cognitive insight but the impact of poor neurocognitions on the clinical insight is not very significant.

Mental health symptoms and verbal fluency in elderly people: Evidence from the Spanish longitudinal study of aging

ABSTRACTObjectives: Depression and loneliness are highly prevalent in old age. Moreover these mental health symptoms adversely affect the verbal fluency of the elderly. We examined the relationship between depression and loneliness with verbal fluency in people aged 50 years or older.Method: Research data were collected during the pilot study of the Longitudinal Aging Study in Spain (ELES) in which a representative sample of non-institutionalized Spanish older people was assessed. Here, the cross-sectional data for 962 participants were analysed using hierarchical regressions, controlling for age, education level, overall cognitive functioning, social networks and satisfaction with family.Results: Higher levels of cognitive functioning were associated with higher verbal fluency. Females showed higher levels of phonological fluency. Neither depression nor loneliness were significant predictors of phonological fluency but loneliness was a significant predictor of semantic fluency. For mild levels of loneliness, the rate of decline in semantic fluency slows in the oldest ages. In contrast, for severe loneliness the rate of decline in semantic fluency increases in the oldest ages.Conclusions: Depressive symptoms, loneliness and cognitive impairment are all prominent in ageing and therefore their impact on ageing needs to be better understood. Early detection of loneliness, along with the implementation of intervention for individuals diagnosed with loneliness is advisable in order to avoid negative repercussions for the verbal fluency of these individuals.

Executive, language, or both? An examination of the construct validity of verbal fluency measures

ABSTRACTThe purpose of the present study was to evaluate whether phonemic and semantic verbal fluency were more related to aspects of language processing than executive functioning (EF). An exploratory factor analysis was performed on a college-aged sample of 320 healthy participants using principle axis factoring and promax rotation on nine measures of EF. The first three factors, labeled: working memory, fluid reasoning, and shifting/updating, were extracted and used as latent executive variables. Participants were also split into low, medium, and high phonemic and semantic verbal fluency ability groups. Phonemic and semantic fluency correlated similarly across all three extracted EF factors and word knowledge. Using one-way analysis of variance (ANOVAs), there was a main effect for both phonemic and semantic verbal fluency groups and all outcome variables (i.e., the EF factors and word knowledge). Tukey HSD post hoc analyses showed that those in the low verbal fluency ability groups had significantly lower scores across all outcome measures compared to the high verbal fluency ability groups. Across all analyses, semantic fluency had stronger relations with the EF factors, signifying a large executive component involved in the task. Both phonemic and semantic fluency were similarly related to multiple dimensions of EF and word knowledge and should be considered executive language tasks.

Similarities and Differences of Neuropsychological Profiles in Children and Adolescents with Anorexia Nervosa and Healthy Controls Using Cluster and Discriminant Function Analyses.

This study aimed to identify discrete neuropsychological profiles and their relationship to clinical symptoms in 253 female children and adolescents with anorexia nervosa (AN) and 170 healthy controls (HCs) using a standardised neuropsychological assessment battery. Hierarchical cluster analysis was used to identify the optimum number of clusters, and participants were assigned using K-means cluster analysis. Confirmatory discriminant function analysis determined which combination of neuropsychological variables best distinguished the clusters. Three distinct clusters in the AN sample emerged- AN cluster 1 (19%) - "neuropsychologically low average to average"; AN cluster 2 (33%) - "verbal/visuo-spatial discrepancy"; and AN cluster 3 (48%) - "verbally strong and neuropsychologically average to high average". Two distinct clusters in HCs were identified. HC cluster 1 (48%) demonstrated poor visuo-spatial memory scores and high verbal fluency scores, whilst HC cluster 2 (52%) scored within the average range on all neuropsychological tasks. Neuropsychological performance was associated with clinical symptoms of body mass index centile, Eating Disorder Examination subscale and global score, anxiety, depression and obsessions, and compulsions between the AN and HC groups. However, niether significant differences emerged between AN clusters only nor HC clusters only at the post-hoc level. An underlying neuropsychological heterogeneity may exist in AN. We encourage future studies to investigate whether the identified profiles and their association with clinical characteristics are replicable. We cautiously suggest that neuropsychological profiling may have potential to both inform future research and have possible clinical benefits through individually tailored treatment strategies.

Cross-age comparisons reveal multiple strategies for lexical ambiguity resolution during natural reading.

Eye tracking was used to investigate how younger and older (60 or more years) adults use syntactic and semantic information to disambiguate noun/verb (NV) homographs (e.g., park). In event-related potential (ERP) work using the same materials, Lee and Federmeier (2009, 2011) found that young adults elicited a sustained frontal negativity to NV homographs when only syntactic cues were available (i.e., in syntactic prose); this effect was eliminated by semantic constraints. The negativity was only present in older adults with high verbal fluency. The current study shows parallel findings: Young adults exhibit inflated first fixation durations to NV homographs in syntactic prose, but not semantically congruent sentences. This effect is absent in older adults as a group. Verbal fluency modulates the effect in both age groups: High fluency is associated with larger first fixation effects in syntactic prose. Older, but not younger, adults also show significantly increased rereading of the NV homographs in syntactic prose. Verbal fluency modulates this effect as well: High fluency is associated with a reduced tendency to reread, regardless of age. This relationship suggests a trade-off between initial and downstream processing costs for ambiguity during natural reading. Together the eye-tracking and ERP data suggest that effortful meaning selection recruits mechanisms important for suppressing contextually inappropriate meanings, which also slow eye movements. Efficacy of frontotemporal circuitry, as captured by verbal fluency, predicts the success of engaging these mechanisms in both young and older adults. Failure to recruit these processes requires compensatory rereading or leads to comprehension failures (Lee & Federmeier, 2012).

Thinking ahead or not? Natural aging and anticipation during reading

Despite growing evidence of young adults neurally pre-activating word features during sentence comprehension, less clear is the degree to which this generalizes to older adults. Using ERPs, we tested for linguistic prediction in younger and older readers by means of indefinite articles (a’s and an’s) preceding more and less probable noun continuations. Although both groups exhibited cloze probability-graded noun N400s, only the young showed significant article effects, indicating probabilistic sensitivity to the phonology of anticipated upcoming nouns. Additionally, both age groups exhibited prolonged increased frontal positivities to less probable nouns, although in older adults this effect was prominent only in a subset with high verbal fluency (VF). This ERP positivity to contextual constraint violations offers additional support for prediction in the young. For high VF older adults, the positivity may indicate they, too, engage in some form of linguistic pre-processing when implicitly cued, as may have occurred via the articles.

Hippocampal sclerosis in advanced age: clinical and pathological features

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.

Differential age effects on lexical ambiguity resolution mechanisms

Multiple neurocognitive subsystems are involved in resolving lexical ambiguity under different circumstances. We examined how processing in these subsystems changes with normal aging by comparing ERP responses to homographs and unambiguous words completing congruent sentences (with both semantic and syntactic contextual information) or syntactic prose (syntactic information only). Like young adults in prior work, older adults elicited more negative N400s to homographs in congruent sentences, suggesting mismatch between the context and residual activation of the contextually irrelevant sense. However, the frontal negativity seen in young adults to homographs in syntactically well-defined but semantically neutral contexts was absent in older adults as a group, suggesting a decline in recruiting additional neural resources to aid difficult semantic selection. A subset of older adults with high verbal fluency maintained a young-like effect pattern.