Roca M, Torralva T, López PL, Marengo E, Cetkovich M, Manes F.  Differentiating early dementia from major depression with the Spanish version of the Addenbrooke’s Cognitive Examination. Revista Neurológica 2008

NTRODUCTION: In clinical practice it is often difficult to establish whether cognitive impairment is secondary to an affective disorder or a dementing process. AIM: To describe the cognitive performance on the Spanish version of the Addenbrooke’s Cognitive Examination (ACE) of patients with early dementia and depression. SUBJECTS AND METHODS: 77 patients with early dementia (53 Alzheimer disease; 24 frontotemporal dementia), 17 patients with major depression and 54 healthy volunteers were tested with the Spanish version of the ACE. RESULTS: Alzheimer disease and frontotemporal dementia groups were significantly lower than the control group and the major depression group. When the major depression group was compared with the control group no significant differences were found. CONCLUSIONS: The cognitive performance in the ACE is different in patients with early dementia and patient with depression.

Regazzoni C, Zamora R, Petrucci E, PIsarevsky A, Ariel Saad, De Mollein D, Luna CM, Poderoso JJ. Hospital and 1-year outcomes of septic syndromes in older people: a cohort study. The journals of gerontology 2008

PURPOSE: Our objective was to describe the relationship between sepsis syndrome mortality and cognitive and physical disability in elderly persons. METHODS: A 1-year consecutive cohort study in clinical beds of a university hospital was performed. Variables were severity of sepsis syndrome, organ failure, functional status, age, sex, and positive cultures. Outcomes were in-hospital and 1-year mortalities. RESULTS: The study included 137 patients (>70 years), both sexes. Data from 116 (84.5%) patients were obtainable at 1-year follow-up. Forty-eight (35%) patients presented with sepsis (11/137, 8%) or severe sepsis (37/137, 27%). In-hospital mortality was 15.3% (0% for sepsis and 21.8% if severe) and increased with organ failure (p <.0001). One-year mortality was 54.78% (63/116), mostly related to severe sepsis; predictors were severe organ failure (p <.0001), prior functional status (p =.0005), and Mini-Mental State Examination (p =.03). Prior functional status and organ failure were independent predictors. CONCLUSIONS: In-hospital and 1-year mortality increased with septic syndrome severity, prior functional status, and organ failure.

Vazquez G, Kahn C, Schiavo C, Goldchluk A, Herbst L, Piccione M, Saidman N, Ruggeri H, Silva A, Leal J, García-Bonetto G,Zariategui R, Padilla E, Vilapriño JJ, Calvó M, Guerrero G, Strejilevich S, Cetkovich M, Akiskal KK, Akiskal HS.  Bipolar disorders and affective temperaments: a national family study testing the «endophenotype» and «subaffective» theses using the TEMPS-A Buenos Aires. Journal of affective disorders 2008

The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these «subaffective » forms on their quality of life (QoL). METHODS: The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients and 115 comparison subjects without family history of affective illness ( «controls «). We used The Mood Disorder Questionnaire to rule out clinical bipolarity. RESULTS: Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic. LIMITATIONS: We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses. CONCLUSIONS: Our findings support the concept of a spectrum of subthreshold affective traits or temperaments – especially for the cyclothymic and anxious – in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in «clinically well » relatives. Overall, our data are compatible with the ;endophenotype; and subaffective theses for affective temperaments.

Torralva T, Roca M, Gleichgerrcht E, López PL, Manes F.  INECO Frontal Screening (IFS): a brief, sensitive, and specific tool to assess executive functions in dementia. Journal of the International Neuropsychological Society 2009

Although several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach’s alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD.

Mehta MA, Manes F, Magnolfi G, Sahakian BJ, Robbins TW. Impaired set-shifting and dissociable effects on tests of spatial working memory following the dopamine D2 receptor antagonist sulpiride in human volunteers. Psychopharmacology 2004

RATIONALE: Dopamine (DA) D(2) receptor antagonists have been shown to produce similar impairments to those seen in Parkinson’s disease. These include working memory and set-shifting deficits. Theories of DA function have predicted that distraction or impaired switching may be important determinants of such deficits. OBJECTIVES: In order to test these hypotheses, we have followed up our previous findings with more refined tests (1) that allow measurement of spatial working memory (SWM) and distraction, (2) that allow separation of executive and mnemonic components of SWM and (3) that allow isolation of set-shifting from learning deficits. METHODS: Thirty-six young healthy male volunteers were tested on two occasions after oral administration of either 400 mg sulpiride or placebo. All participants performed the delayed response task. Sixteen participants received task-irrelevant distractors during this task, and were also given a self-ordered SWM test. The remaining participants were given delayed response tasks with task-relevant distractors, and tests of attentional and task set-shifting. RESULTS: Sulpiride impaired performance of the delayed-response task both without distraction and with task-relevant distraction. By contrast, the drug protected against deficits from task-irrelevant distraction seen in the placebo group. Task set-switching was also impaired by sulpiride, with participants being slower to respond on switch trials compared with non-switch trials. There was also a trend for attentional set-shifting to be impaired following sulpiride. In contrast, self-ordered SWM performance was enhanced by sulpiride on the second test session only. CONCLUSIONS: These results support models of central DA function that postulate a role in switching behaviour, and in certain aspects of working memory.

Martino D, Strejilevich S, Scapola M, Igoa A, Marengo E, Ais E, Perinot L.  geneity in cognitive functioning among patients with bipolar disorder. Behavioural Neurology 2008

BACKGROUND: Nowadays it is not clear if in bipolar disorders (BD) cognitive impairments are heterogeneous and if so which are the variables that determine it. METHODS: Fifty patients with BD and thirty healthy controls were clinically evaluated including measures of obstetric complications history. All subjects completed an extensive neuropsychological battery selected to asses premorbid IQ and different cognitive domains. RESULTS: Compared with standardized norms, 38% of patients had none cognitive domain affected, while 40% had 1 to 2, and 22% had 3 to 5. Patients with cognitive functioning within normal limits had higher psychosocial functioning and premorbid IQ, and lower history of obstetric complications. LIMITATIONS: The small sample size could limit the generalizability of the results; since these data should be taken as preliminaries. CONCLUSIONS: The extension and severity of cognitive impairments may be heterogeneous in patients with BD, and it might contribute to explain the variability in functional outcome. Bipolar patients with low premorbid IQ and history of obstetric complications may represent a subgroup with lower cognitive performance and psychosocial functioning.

Lansing AE, Max JE, Delis DC, Fox PT, Lancaster J, Manes F, Schatz A.  Verbal learning and memory after childhood stroke. Journal of the International Neuropsychological Society 752.[PubMed] ver 2004 doi: 10.1016/B978-0-444-52892-6.00013-1.

Verbal learning and memory (VLM) following pediatric stroke was characterized in a cross-sectional neuropsychological and neuroimaging study of 26 subjects, aged 5 to 17, with a history of pediatric stroke and 26 age, SES, and gender matched orthopedic controls. Further comparisons were made between the VLM profiles of stroke subjects with right versus left hemisphere lesions and early ( < 12 months) versus late (12 months) strokes. Overall, stroke subjects scored significantly lower than control subjects on several VLM indices (California Verbal Learning Test-Children; CVLT-C), as well as on measures of intellectual functioning (IQ) and auditory attention/working memory (Digit Span). Subgroup analyses of the stroke population found no significant differences in VLM, Digit Span, Verbal IQ or Performance IQ when left-hemisphere lesion subjects were compared to right-hemisphere lesion subjects. In contrast, early strokes were associated with significantly fewer words recalled after delay, reduced discriminability (fewer correct hits relative to false positive errors on recognition testing), and relatively worse auditory attention/working memory scores (Digit Span). These findings indicate that pediatric stroke subjects demonstrated more VLM impairment than control subjects, and early strokes were associated with greater recall and recognition deficits. In stark contrast with adult-onset stroke, both left- and right-hemisphere lesions during childhood resulted in similar VLM performance.

Roca M, Torralva T, López PL, Cetkovich M, Manes F.  Executive functions in pathologic gamblers selected in an ecologic setting. Cognitive and Behavioral Neurology 2008

BACKGROUND: Recent studies have reported deficits in measures of decision making in pathologic gamblers (PGs) suggesting an involvement of the prefrontal cortex in the pathophysiology of this disorder. As only 7% to 12% of PGs are thought to seek treatment, most of the studies have relied on few specifically selected groups of PGs recruited from psychiatric units who were undergoing or seeking treatment and therefore their results are poorly representative of the general PG population. METHODS: The present study compared decision making and executive functions among 11 PGs who were selected from an ecologic setting and 11 healthy controls. RESULTS: The PG group selected fewer advantageous cards on a decision-making task, the Iowa Gambling Task, and made more commission errors on the Go-No Go task, a test of inhibitory control, compared with controls. CONCLUSIONS: The impairments in decision making are similar to those previously reported in individuals with prefrontal lesions and treatment-seeking PGs. PGs also presented impairment in tasks of inhibitory control suggesting an involvement of the prefrontal cortex in the pathophysiology of pathologic gambling (PG). The deficits in decision making and inhibition of irrelevant information observed in this study may have distinct but additive effects upon the development of PG behavior.

Max JE, Robin DA, Taylor HG, Yeates KO, Fox PT, Lancaster J, Manes F, Mathews K, Austeman S.  Attention function after childhood stroke. Journal of the International Neuropsychological Society 2004

We investigated attentional outcome after childhood stroke and orthopedic diagnosis in medical controls. Twenty-nine children with focal stroke lesions and individually matched children with clubfoot or scoliosis were studied with standardized attention and neuroimaging assessments. Stroke lesions were quite varied in location and commonly involved regions implicated in Posner’s model of attention networks. Children with stroke lesions performed significantly more poorly regarding attention function compared with controls. Performance on the Starry Night, a test demanding alerting and sensory-orienting but not executive attention function, was significantly associated with lesion size in the alerting and sensory-orienting networks but not the executive attention network. Furthermore, earlier age at lesion acquisition was significantly associated with poorer attention function even when lesion size was controlled. These findings support the theory of dissociable networks of attention and add to evidence from studies of children with diffuse and focal brain damage that early insults are associated with worse long-term outcomes in many domains of neuropsychological function. In addition, these results may provide clues towards the understanding of mechanisms underlying attention in children.