Javier Peña

Processing speed mediates the relationship between verbal memory, verbal fluency, and functional outcome in chronic schizophrenia

Verbal fluency and verbal memory have been reported to be diminished in patients with schizophrenia. These deficits could partially predict functional disability in this pathology. However, processing speed often mediates the relationship among cognitive processes in the disorder. Our goal was to analyse the influence of processing speed as mediator of the relation between verbal fluency-verbal memory and functional disability in chronic schizophrenia. We examined 90 hospitalized patients and 30 healthy controls (matched for gender, age and years of education). The neuropsychological battery included tests for verbal fluency, verbal memory, motor speed and processing speed. Outcome measures included Disability Assessment Schedule (DAS-WHO) and number of hospitalizations (NH). Results confirmed chronicity on clinical symptoms (PANSS total X=48.94+14.97 PANSS negative X=27.81+10.18, PANSS positive X=23.51+10.81) and impairment on functional disability (DAS-WHO X=13.62+4.28). As expected, verbal fluency was severely impaired in patients and significantly predicted functional outcome. Immediate and Delayed Verbal Memory were also severely impaired and predicted functional outcome. However, when processing speed was entered in the regression analyses the significance of verbal fluency and verbal memory decreased significantly. Sobels equation was significant, suggesting full mediation. Our findings suggest that processing speed may be a central factor in the relation between cognitive symptoms and functional outcome in chronic schizophrenia.

Hierarchical structure of the cognitive processes in schizophrenia: the fundamental role of processing speed

OBJECTIVE Decreased processing speed (PS) is a key feature of schizophrenia with respect to cognition, functional outcome and clinical symptoms. Our objective was to test whether PS slowing mediates other neuropsychological deficits among patients with chronic schizophrenia. METHOD One hundred patients with schizophrenia and 53 healthy adults completed a series of neuropsychological measures that assess six cognitive domains. In addition to PS these included attention, verbal memory, visual memory, working memory, and executive functioning. Confirmatory factor analysis (CFA) was used to evaluate the fit of the 6-factor model. The cognitive performances of both groups were compared before and after controlling for the effect of PS, but also after controlling for the effect of each cognitive factor at a time. Finally, the PS-related variance was removed and the effect of the other cognitive factors was tested again. RESULTS CFA supported the hypothesized 6-factor cognitive structure. As expected, the patients and controls differed on all cognitive measures. However, after controlling for the effects of PS, group differences on the other five cognitive factors decreased substantially. Controlling for other factors produced smaller attenuation of group differences, and these effects were also partially accounted for by decreased PS. CONCLUSIONS PS deficits account for most of the differences in cognition between patients with schizophrenia and healthy controls. PS slowing appears to be a core feature of schizophrenia, one that underlies impairments of working memory, executive functioning, and other abilities.

Improving functional disability and cognition in Parkinson disease: Randomized controlled trial

Objectives: To examine the efficacy of an integrative cognitive training program (REHACOP) to improve cognition, clinical symptoms, and functional disability of patients with Parkinson disease (PD). Methods: Forty-two patients diagnosed with PD in Hoehn & Yahr stages 1 to 3 were randomly assigned to either the cognitive training group (REHACOP) or the control group (occupational activities) for 3 months (3 sessions, 60 min/wk). Primary outcomes were change on processing speed, verbal memory, visual memory, executive functioning, and theory of mind. Secondary outcomes included changes on neuropsychiatric symptoms, depression, apathy, and functional disability. The trial was registered with clinicaltrials.gov (NCT02118480). Results: No baseline group differences were found. Bootstrapped analysis of variance results showed significant differences in the mean change scores between the REHACOP group and control group in processing speed (0.13 [SE = 0.07] vs −0.15 [SE = 0.09], p = 0.025), visual memory (0.10 [SE = 0.10] vs −0.24 [SE = 0.09], p = 0.011), theory of mind (1.00 [SE = 0.37] vs −0.27 [SE = 0.29], p = 0.013), and functional disability (−5.15 [SE = 1.35] vs 0.53 [SE = 1.49], p = 0.012). Conclusions: Patients with PD receiving cognitive training with REHACOP demonstrated statistically significant and clinically meaningful changes in processing speed, visual memory, theory of mind, and functional disability. Future studies should consider the long-term effect of this type of intervention. These findings support the integration of cognitive training into the standard of care for patients with PD. Classification of evidence: This study provides Class II evidence that for patients with PD, an integrative cognitive training program improves processing speed, visual memory, theory of mind, and functional disability.

Verbal fluency in schizophrenia: does cognitive performance reflect the same underlying mechanisms in patients and healthy controls?

Verbal fluency is impaired in patients with schizophrenia, but the association with other cognitive domains remains unclear. Forty-seven patients with schizophrenia (DSM-IV) and 47 controls matched by age, gender, years of education, and vocabulary (Wechsler Adult Intelligence Scale-III) were assessed in terms of sociodemographic, clinical, and cognitive variables. Healthy controls performed significantly better than patients with schizophrenia in all cognitive measures. However, the way these cognitive domains were related differed across groups. Semantic fluency (SF) and phonological fluency (PF) were predicted by working memory (WM) in patients with schizophrenia, whereas the predictor in the healthy controls was processing speed (PS). Moreover, after dividing the sample of patients according to their performance on fluency tests, we found that a worse performance on SF or PF was predicted by WM. However, for patients with a better performance on fluency, the pattern was similar to that of healthy controls. Cognition may show a different pattern of interaction in schizophrenia, with less impaired patients showing a closer pattern to healthy controls. Therefore, we suggest that, depending on the severity of cognitive deficits, performance on neuropsychological tests may not reflect the same underlying mechanisms.

Longitudinal changes of insight in first episode psychosis and its relation to clinical symptoms, treatment adherence and global functioning: one-year follow-up from the Eiffel study.

OBJECTIVES The Eiffel study is a longitudinal, naturalistic study of patients with first episode psychosis (FEP) designed to evaluate the predictive value of defective insight on treatment adherence and global functioning. METHODS Five hundred seventy-seven patients with FEP were assessed at baseline and at a 1-year follow-up. They were compared in terms of sociodemographic factors, psychopathology, insight, treatment adherence and functional outcome. Longitudinal functionality was prospectively assessed with the clinical global impression (CGI) and global assessment of functioning (GAF) rating scales. RESULTS At baseline, up to 50% of our sample presented with a lack of insight. Most clinical symptoms, including insight, improved over the follow-up period. Insight, education and social withdrawal significantly predicted CGI and GAF at follow-up. Insight and level of education were predictive of treatment adherence. CONCLUSIONS Insight significantly predicted the general clinical course, treatment adherence and functional outcome in our FEP sample after 1 year. Only education additionally accounted for the longitudinal course. Since our results suggest that better insight improves treatment adherence and consequently clinical course and functional outcome, insight could be a specific target of treatment in early intervention programs.

The source of the memory impairment in Parkinson's disease: Acquisition versus retrieval

Memory deficits are common in persons with Parkinsons disease (PD) even without the presence of a frank dementia. These memory deficits have traditionally been attributed to inability of patients to retrieve information from long‐term memory, referred to as the “retrieval failure hypothesis.” However, some studies additionally document problems in recognition memory, noted to be inconsistent with the retrieval failure hypothesis. Given the neuroanatomical abnormalities observed in the hippocampus of PD patients and the role of the hippocampus in learning new information, the current study was designed to specifically examine learning abilities in a nondemented PD sample through the application of a learning paradigm, the Open Trial Selective Reminding Test. We examined 27 patients with PD without dementia and 27 age‐, gender‐, and education‐matched healthy controls (HCs) with a neuropsychological test battery designed to assess new learning and memory. Results indicated a significant difference between the groups in terms of their ability to learn a list of 10 semantically related words. However, once the groups were equated on learning abilities, no significant difference was noted between the PD and HC participants in recall or recognition of the newly learned material. The memory deficit observed in nondemented PD patients is thus largely the result of a deficit in learning new information. This finding should be used to guide treatment for memory deficits in persons with PD, and future research should seek to identify novel means of improving new learning in this population.

Confirmatory factor analysis reveals a latent cognitive structure common to bipolar disorder, schizophrenia, and normal controls.

We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups.

Do the same factors predict outcome in schizophrenia and non-schizophrenia syndromes after first-episode psychosis? A two-year follow-up study

OBJECTIVE The aim of this two-year longitudinal study was to identify the best baseline predictors of functional outcome in first-episode psychosis (FEP). We tested whether the same factors predict functional outcomes in two different subsamples of FEP patients: schizophrenia and non-schizophrenia syndrome groups. METHODS Ninety-five patients with FEP underwent a full clinical evaluation (i.e., PANSS, Mania, Depression and Insight). Functional outcome measurements included the WHO Disability Assessment Schedule (DAS-WHO), Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI). Estimation of cognition was obtained by a neuropsychological battery which included attention, processing speed, language, memory and executive functioning. RESULTS Greater severity of visuospatial functioning at baseline predicted poorer functional outcome as measured by the three functional scales (GAF, CGI and DAS-WHO) in the pooled FEP sample (explaining ut to the 12%, 9% and 10% of the variance, respectively). Negative symptoms also effectively contributed to predict GAF scores (8%). However, we obtained different predictive values after differentiating sample diagnoses. Processing speed significantly predicted most functional outcome measures in patients with schizophrenia, whereas visuospatial functioning was the only significant predictor of functional outcomes in the non-schizophrenia subgroup. CONCLUSIONS Our results suggest that processing speed, visuospatial functioning and negative symptoms significantly (but differentially) predict outcomes in patients with FEP, depending on their clinical progression. For patients without a schizophrenia diagnosis, visuospatial functioning was the best predictor of functional outcome. The performance on processing speed seemed to be a key factor in more severe syndromes. However, only a small proportion of the variance could be explained by the model, so there must be many other factors that have to be considered.

Executive functioning correctly classified diagnoses in patients with first-episode psychosis: evidence from a 2-year longitudinal study.

Few studies have analysed factors that predict the ultimate clinical diagnosis in first-episode psychosis (FEP), and none has included cognitive factors. Eighty-six FEP patients and 34 healthy controls were recruited and followed up for two years. Positive and negative symptoms, depression, mania, duration of untreated psychosis (DUP), premorbid functioning, functional outcome and neurocognition were assessed over 2 years. Logistic regression models revealed that Wisconsin Card Sorting Test correctly distinguished the patients ultimately diagnosed with schizophrenia (87%) from those with bipolar disorder (80%) and those with other psychoses (85%), for an overall correct-diagnosis rate of 84.4%. The prediction was stable despite the inclusion of clinical and affective symptoms, DUP, clinical impression, and functional outcome scores. Results highlight the importance of reconsidering neurocognition as a diagnostic criterion for psychosis and schizophrenia.

Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson's disease

OBJECTIVE To assess whether functional neural connectivity is disrupted between the regions of the default mode network (DMN) in Parkinsons disease (PD) and how this connectivity is related to cognition, brain gray matter structure and white matter integrity and diffusivity. METHODS Thirty-seven PD patients and 16 healthy controls were evaluated, using resting-state functional magnetic resonance imaging (MRI), T1-weighted MRI, diffusion-weighted imaging and a battery of cognitive tests. Functional connectivity between the regions of the DMN, specifically in the precuneus, anterior and posterior cingulate, medial prefrontal and temporal and inferior parietal cortices was assessed with seed-to-voxel connectivity; gray matter volume and white matter values were determined using voxel-based morphometry and tract-based spatial statistics. RESULTS Reduced functional connectivity was observed between the posterior cingulate and medial temporal lobe in PD. Lower cognitive performance, gray matter loss in posterior, medial temporal and parietal areas, and fractional anisotropy reduction in the white matter adjacent to DMN regions were also observed in PD patients compared with healthy controls. Lower DMN functional connectivity correlated with lower verbal and visual memory and visual abilities performance in PD. In addition, lower DMN functional connectivity correlated with lower gray matter volume in the posterior cingulate and precuneus, and with lower white matter fractional anisotropy of the inferior longitudinal and posterior cingulate fasciculi in PD. CONCLUSIONS By combining different neuroimaging techniques and cognitive data, results showed that functional connectivity alteration between the regions of the DMN is associated with lower cognitive performance and gray and white matter abnormalities in PD.