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.

Martino D, Igoa A, Marengo E, Scapola M, Ais E, Strejilevich S.  Cognitive and motor features in elderly people with bipolar disorder. Journal of affective disorders 2008

Although elderly people will represent one third of the bipolar population in a few years, data about cognitive and motor features in these patients are very scarce. The aim of this study was to compare the cognitive and motor functioning between elderly euthymic patients with bipolar disorder (BD) and healthy controls, as well as to determine the degree of correlation with psychosocial functioning. METHODS: Euthymic older adults with BD (n=20) and healthy controls (n=20) were evaluated with traditional clinical instruments and measures of exposure to psychotropic drugs and extrapyramidal symptoms. All subjects completed an extensive neuropsychological battery. RESULTS: Patients with BD had more extrapyramidal symptoms and worse performance than healthy controls in psychomotor speed, verbal memory, and executive functions even after controlling sub-clinical symptomatology. These findings were not associated with age at onset or length of illness or with current pharmacological exposure. Psychosocial functioning correlated negatively with performance in psychomotor speed and executive function, and with extrapyramidal symptoms. LIMITATIONS: The small sample size and cross-sectional design. CONCLUSIONS: Older adult patients with BD in a euthymic state could have a similar cognitive and motor profile to that described in younger euthymic bipolar patients. Cognitive-motor disturbances may help to explain impairments in daily functioning among elderly patients with bipolar disorder during remission.

Fleischhacker WW, Cetkovich M, DeHert M, Hennekens C, Lambert M, Leucht S, Maj M, McIntyre R, Naber D, Newcomer J,Olfson M, Osby U, Sartorius N, Lieberman J.  Comorbid somatic illnesses in patients with severe mental disorders: clinical, policy, and research challenges. The Journal of clinical psychiatry 2008

BACKGROUND: An increasing body of evidence suggests that, in comparison to the general population, patients with severe mental illnesses such as schizophrenia or bipolar disorder have worse physical health and a far shorter life expectancy in developed countries, due primarily to premature cardiovascular disease. PARTICIPANTS: This article is based on presentations and discussion on somatic comorbidity in psychiatric illnesses by a group of 37 international experts during 2 meetings held in 2006. CONSENSUS PROCESS: At the preparatory meeting in Paris, France, the group determined key topics for presentations and group discussions. During the meeting in Vienna, Austria, on day 1, each set of presentations was followed by discussions in small groups with the meeting participants. On day 2, conclusions reached by each discussion group were presented and used as a platform for a consensus view adopted by the meeting participants. The presentations and discussions were collated into a draft that was revised and approved by each of the bylined authors. EVIDENCE: General health care needs are commonly neglected in patients with severe mental illness, with suboptimal integration of general somatic and psychiatric care services, current lack of consensus as to which health care professionals should be responsible for the prevention and management of comorbid somatic illnesses in patients with severe mental disorders, and, at least in some countries, a paucity of funding for general somatic care for patients with severe mental disorders, especially those in long-term psychiatric treatment. CONCLUSIONS: The somatic health of patients with severe medical illnesses is too often neglected, thus contributing to an egregious health disparity. The reintegration of psychiatry and medicine, with an ultimate goal of providing optimal services to this vulnerable patient population, represents the most important challenge for psychiatry today, requiring urgent and comprehensive action from the profession toward achieving an optimal solution.

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.

Roca M, Torralva T, Meli F, Fiol M, Calcagno ML, Carpintiero S, De Pino G, Ventrice F, Martin-Reyes M, Vita L, Manes F,Correale J.  Cognitive deficits in multiple sclerosis correlate with changes in fronto-subcortical tracts. Multiple Sclerosis 2008

Cognitive function and diffusion tensor imaging were assessed in a group of 12 patients with early relapsing-remitting multiple sclerosis (disease duration 3 years), and mild clinical disability (expanded disability status scale =2), as well as in 12 control subjects. Patients showed impairment in immediate logical memory and delayed recall with the Rey auditory verbal learning test. No significant differences in classical executive tests were observed. In contrast, differences were found for specific executive tests including IOWA Gambling Task, multiple errands test hospital version (MET) and Hotel Task, as well as in Paced-Auditory Serial Addition Test (PASAT). Significant correlation was found between PASAT performance and FA measures (r = 0.64, P = 0.03), the apparent diffusion coefficients and the MET (r = 0.72, P = 0.01), as well as in one subtask of Hotel (r = -0.68, P = 0.02). Thus, executive deficits can best be appreciated at early stages of MS when a more specific battery of tests is used for patient evaluation. In this series, test failures observed correlated with changes in fronto-subcortical fiber tracts.